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PubMed1999

Chemical heterogeneity of the striosomal compartment in the human striatum.

The neurochemical organization of the striosomal compartment in the human striatum was analyzed by histochemical and immunohistochemical techniques applied to postmortem tissue from normal individuals. The striosomes were delineated by using the following markers: acetylcholinesterase (AChE), enkephalin (ENK), substance P (SP), calbindin-D28k (CB), parvalbumin (PV), calretinin (CR), limbic system-associated membrane protein (LAMP), choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), and NADPH-diaphorase. Comparisons were made between striosomal boundaries, as outlined by each marker applied on adjacent sections, and particular attention was paid to possible variations in the chemical features of striosomes along the rostrocaudal extent of the striatum. The main findings of this study are as follows: 1) the striosomal compartment is composed of two chemically distinct domains: a core and a peripheral region; 2) the core is largely devoid of CB and displays a less intense staining for ENK and LAMP than the peripheral region; 3) although striosomes are largely devoid of AChE, the activity of this enzyme is slightly higher in the core than in the peripheral region; 4) the core and peripheral regions are weakly stained for PV and intensely stained for SP; 5) ChAT-, CR- and NADPH-diaphorase-positive neurons are preferentially distributed in the peripheral region; 6) at rostral striatal levels, striosomes are largely devoid of TH, whereas the inverse is true caudally; and 7) at caudal striatal levels, the peripheral region of striosomes is intensely stained for CB and ChAT. These results demonstrate that the striosomes in human display a strikingly complex and heterogeneous chemical architecture.

Acetylcholinesterase↗
PubMed1990

Calcium binding protein (calbindin-D28k) gene expression in the developing and aging mouse cerebellum.

Calbindin-D28k (CaBP28k) protein and gene expression were examined in the mouse cerebellum during development and aging utilizing slot and Northern blot hybridization analyses for mRNA levels, Western blot analysis and radioimmunoassay (RIA) for protein levels, and by in situ studies using immunocytochemistry and hybridization cytochemistry on prepared tissue sections. Samples were obtained and analyzed from C57BL/6J mice aged day of birth and postnatal weeks 1, 2, 4, 8, and 120. A specific cDNA and antibody for CaBP28k were utilized in these studies. Analysis of mRNA levels showed a steady rise in CaBP28k mRNA from birth to a peak at postnatal week (3.4-fold increase) and then a decline to steady-state levels at postnatal weeks 4 and 8 (47% reduction of peak level) followed by a reduction of CaBP28k mRNA to birth levels at postnatal week 120. The specificity of the changes observed was tested by reprobing blots with beta-actin cDNA. Analysis of CaBP28k protein levels by both Western blot and RIA showed a similar pattern. In situ analysis of CaBP28k mRNA levels, based on hybridization signal (silver grains per cell), demonstrated a rise in cellular CaBP28k mRNA levels which peaked at postnatal week 2 (416.9 +/- 52.1) and then declined to steady-state levels by postnatal weeks 4 and 8 (267.4 +/- 35.8). Cellular CaBP28k mRNA levels exhibited a dramatic reduction in the aged cerebellum (postnatal week 120; 78.3 +/- 16.0). The levels of cellular CaBP28k mRNA corresponded to the intensity of immunoreactive CaBP28k localized by immunocytochemistry. The results are consistent with the hypothesis that CaBP28k may play a critical role in Purkinje cell maturation and maintenance.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed2000

Regulation of renal calbindin-D28K.

Calbindin-D28k is an intracellular protein with high affinity for calcium. In the kidney, this protein is exclusively localized in the distal tubule and in the proximal part of the collecting ducts. Functionally, calbindin-D28k is supposed to be involved in the regulation of the reabsorption of calcium and possibly magnesium in the distal nephron though the exact regulatory mechanisms are not yet known. Thus, several theories regarding the functional role of calbindin-D28k have been proposed: The carrier theory describes calbindin-D28k as a transport protein which binds calcium and then transports it from the luminal to the basolateralcell membrane. The buffer theory assumes that calbindin-D28k functions by binding calcium ions to prevent intracellular calcium concentrations from reaching toxic levels. The activator theory describes that calbindin-D28k increases the activity of calcium channels or the enzymatic activity of the Ca++-Mg++-ATPase in the luminal membrane and thereby increases the tubular reabsorption of calcium. The renal calbindin-D28k is dependent upon vitamin D. Pharmacological doses of the active vitamin D metabolite 1,25-(OH)2D increases the concentrations of renal calbindin-D28k, whereas the concentration of calbindin-D28k is low in conditions with reduced levels of circulating 1,25-(OH)2D. Likewise, plasma calcium concentrations, uremia and hypertension affect calbindin-D28k expression. However, several studies have rendered probable the effect of additional factors in the regulation of renal calbindin-D28k. The aim of the present dissertation therefore was to examine the regulation of renal calbindin-D28k in a series of physiological and pathophysiological conditions established in vivo in the rat. A possible correlation between hypertension and calbindin-D28k was examined in three models of experimental hypertension: the genetically defined spontaneous hypertensive rat, the salt-sensitive Dahl rat and the renovascular hypertensive rat. These three models clearly demonstrated three separate patterns in the calcium metabolism, but the studies were unable to support a role for calbindin-D28k in the development of hypertension. In all three models the development of hypertension caused an increased plasma 1,25-(OH)2D. This increase was accompanied by either unaltered or reduced levels of renal calbindin-D28k possibly secondary to a cellular resistance against 1,25-(OH)2D. Magnesium binds to calbindin-D28k with a relatively high affinity. The regulation of urinary magnesium excretion takes place in the distal tubule where calbindin-D28k is found in high concentrations. Therefore, a possible relation between magnesium and calbindin-D28k was examined. The studies demonstrated not previously known connections between magnesium intake, urinary magnesium excretion and renal calbindin-D28k which suggests that this protein is involved in the regulation of magnesium homeostasis by the kidney. Calcitonin increases the reabsorption of calcium in the distal tubule. Therefore, the effect ofcalcitonin on renal calbindin-D28k was examined both by eliminating the endogeneous calcitonin production by a selective thyroidectomy followed by an autotransplantation of the parathyroid glands and further by infusion of calcitonin. These studies demonstrated unchanged concentrations of renal calbindin-D28k. It was concluded that the increased calcium reabsorption induced by calcitonin in the distal tubule is not mediated by calbindin-D28k. Urinary calcium excretion is in part regulated by the action of PTH on calcium reabsorption in the distal nephron. Previous reports of increased expression of renal calbindin-D28k in uremic rats led us to suggest that secondary hyperparathyroidism associated with uremia induced the synthesis of renal calbindin-D28k. Therefore, the effect of PTH was examined in a study comprising selective parathyroidectomy and infusions of PTH, PTHrP, 1,25-(OH)2D and calcium. (ABSTRACT TRUNCATED)

Animals↗
PubMed2001

Calbindin d28k overexpression protects striatal neurons from transient focal cerebral ischemia.

BACKGROUND AND PURPOSE: Increased intracellular calcium accumulation is known to potentiate ischemic injury. Whether endogenous calcium-binding proteins can attenuate this injury has not been clearly established, and existing data are conflicting. Calbindin D28K (CaBP) is one such intracellular calcium buffer. We investigated whether CaBP overexpression is neuroprotective against transient focal cerebral ischemia. METHODS: Bipromoter, replication-incompetent herpes simplex virus vectors that encoded the genes for cabp and, as a reporter gene, lacZ were used. Sprague-Dawley rats received bilateral striatal injections of viral vector 12 to 15 hours before ischemia onset. With the use of an intraluminal occluding suture, animals were subjected to 1 hour of middle cerebral artery occlusion followed by 47 hours of reperfusion. Brains were harvested and stained with X-gal (to visualize beta-galactosidase, the gene product of lacZ). The number of remaining virally transfected, X-gal-stained neurons in both the ischemic and contralateral striata were counted and expressed as the percentage of surviving neurons in the ischemic striatum relative to the contralateral nonischemic striatum. RESULTS: Striatal neuron survivorship among cabp-injected animals was 53.5+/-4.1% (n=10) versus 26.8+/-5.4% among those receiving lacZ (n=9) (mean+/-SEM; P<0.001). CONCLUSIONS: We conclude that viral vector-mediated overexpression of CaBP leads to neuroprotection in this model of central nervous system injury. This is the first demonstration that CaBP overexpression protects neurons in a focal stroke model.

Animals↗
PubMed2006

Subpopulations of neurons expressing parvalbumin in the human amygdala.

Amygdalar intrinsic inhibitory networks comprise several subpopulations of gamma-aminobutyric acidergic neurons, each characterized by distinct morphological features and clusters of functionally relevant neurochemical markers. In rodents, the calcium-binding proteins parvalbumin (PVB) and calbindin D28k (CB) are coexpressed in large subpopulations of amygdalar interneurons. PVB-immunoreactive (-IR) neurons have also been shown to be ensheathed by perineuronal nets (PNN), extracellular matrix envelopes believed to affect ionic homeostasis and synaptic plasticity. We tested the hypothesis that differential expression of these three markers may define distinct neuronal subpopulations within the human amygdala. Toward this end, triple-fluorescent labeling using antisera raised against PVB and CB as well as biotinylated Wisteria floribunda lectin for detection of PNN was combined with confocal microscopy. Among the 1,779 PVB-IR neurons counted, 18% also expressed CB, 31% were ensheathed in PNN, and 7% expressed both CB and PNN. Forty-four percent of PVB-IR neurons did not colocalize with either CB or PNN. The distribution of each of these neuronal subgroups showed substantial rostrocaudal gradients. Furthermore, distinct morphological features were found to characterize each neuronal subgroup. In particular, significant differences relative to the distribution and morphology were detected between PVB-IR neurons expressing CB and PVB-IR neurons wrapped in PNNs. These results indicate that amygdalar PVB-IR neurons can be subdivided into at least four different subgroups, each characterized by a specific neurochemical profile, morphological characteristics, and three-dimensional distribution. Such properties suggest that each of these neuronal subpopulations may play a specific role within the intrinsic circuitry of the amygdala.

Adult↗
PubMed1996

Relationship between calbindin-D28K levels in the A and B cells of the rat endocrine pancreas and the secretion of insulin and glucagon: influence of vitamin D3 deficiency and 1,25-dihydroxyvitamin D3.

The pancreatic B cell is equipped with specific receptors for 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and contains vitamin D-dependent calcium binding proteins (calbindin-D). Insulin secretion is impaired by vitamin D deficiency and is restored by 1,25-(OH)2D3 (concomitantly with an improved calcium handling within B cells) but the effect of 1,25-(OH)2D3 on the pancreatic B cell via calbindin-D is unclear. Therefore we examined the relationship between calbindin-D28K or calbindin-D9K and the activity of the endocrine pancreas in normal (N), four week vitamin D-deficient (-D) and one week 1,25-(OH)2D3-replete (+D) rats. Calbindin-D9K was not found in the pancreas, neither in the islets nor in the exocrine part, of any of the groups of rats (N, -D, or+D). Surprisingly, total islet calbindin-D28K content was increased by vitamin D deficiency and partly restored by 1,25-(OH)2D3. Calbindin-D28K immunostaining was observed only on A and B cells in the endocrine part of the pancreas, the greatest staining being found in A cells. This difference in staining density was increased by vitamin D deficiency and decreased by 1,25-(OH)2D3 treatment. In vitro, 1,25-(OH)2D3 also produced a negative influence on calbindin-D28K staining in A cells, as demonstrated using pieces of pancreas incubated with the steroid for 2 h. No significant influence on labeling intensity of B cell calbindin-D28K could be shown. Plasma insulin and islet insulin release in response to 10 mM arginine stimulation were decreased in -D rats and enhanced in +D rats towards N values. In contrast, plasma glucagon and the amount of glucagon secretion, stimulated in vitro by 10 mM arginine or by low (1.7 mM) glucose concentration, was increased in -D rats and attenuated by 1,25-(OH)2D3. Thus there appears to be no relationship between the steady state level of B cell calbindin-D28K and the regulation of insulin secretion by 1,25-(OH)2D3 in vitamin D-deficient rats. However there is a correlation between A cell calbindin-D28K and glucagon secretion, which are both negatively regulated by 1,25-(OH)2D3. The predominance of calbindin-D28K in A cells raises the question as to how A and B cells interact and the role of calbindin-D28K in calcium handling.

Animals↗
PubMed1998

Morphological features of neurons containing calcium-binding proteins in the human striatum.

An immunohistochemical approach was used to characterize the morphological phenotype of neurons containing the calcium-binding proteins calretinin (CR), parvalbumin (PV), or calbindin-D28k (CB) in the normal human striatum. The protein CR occurs in at least four morphologically distinct types of neurons. Apart from the numerous medium-sized aspiny interneurons and the less abundant giant aspiny interneurons, CR also labels some medium-sized spiny neurons morphologically identical to striatal projection neurons. This finding indicates that CR is not only confined to striatal interneurons but also may be involved in the function of certain projection neurons. Some small and peculiar bushy-like aspiny neurons also are enriched with CR. These neurons could correspond to the dwarf or neurogliform neurons first described by Ramón y Cajal (1911). Three types of PV-immunoreactive striatal neurons can be visualized in the human striatum: 1) the common medium-sized aspiny leptodendritic neurons, 2) some smaller and profusely arborized aspiny neurons, and 3) a few large and intensely stained neurons with conspicuously beaded and poorly branched dendrites. The protein CB labels virtually all medium-sized spiny projection neurons located in the striatal matrix but also identifies a small subset of large and more intensely immunostained aspiny neurons. The latter finding indicates that CB is not entirely confined to striatal projection neurons but also may play a role in local circuit neurons. These normative data should help our understanding of the chemical anatomy of the human striatum in both health and disease.

Adult↗
PubMed2001

Calcium buffering and protection from excitotoxic cell death by exogenous calbindin-D28k in HEK 293 cells.

Calbindin-D28k (CaBP) is a calcium-binding protein found in specific neuronal populations in the mammalian brain that, as a result of its proposed calcium-buffering action, may protect neurons against potentially harmful increases in intracellular calcium. We have stably transfected HEK 293 cells with recombinant human CaBP in order to determine the influence of this protein upon transient increases in intracellular ionic calcium concentration ([Ca(2+)](i)) induced either by transient transfection of the NR1 and NR2A subunits of the N-methyl-D-aspartate (NMDA) receptor and brief exposure to glutamate, photolysis of the caged calcium compound NP-EGTA, or exposure to the Ca(2+)]-ionophore 4-Br-A23187. The presence of CaBP did not significantly reduce the peak [Ca(2+)](i)stimulated by glutamate activation of NMDA receptors but significantly prolonged the recovery to baseline values. Flash photolysis of NP-EGTA in control cells resulted in an almost instantaneous increase in [Ca(2+)](i)followed by a bi-exponential recovery to baseline values. In cells stably expressing CaBP, the peak [Ca(2+)](i)levels were not statistically different from the controls, however, there was a significant prolongation of the initial portion of the slow recovery phase. In cells exposed to 4-Br-A23187, the presence of CaBP significantly reduced the rate of rise of [Ca(2+)](i), reduced the peak response, slowed the rate of recovery, and reduced the depolarization of mitochondria. In studies of delayed, Ca(2+)]-dependent cell death, CaBP transfected cells exhibited enhanced survival 24h after a 1-h exposure to 200 microM NMDA. However, necrotic cell death observed after the first 6h was not prevented by the presence of CaBP. These results provide direct evidence for a Ca(2+)-buffering effect of CaBP which serves to limit Ca(2+)entry and the depolarization of mitochondria, thereby protecting cells from death mediated most likely by apoptosis.

Animals↗
PubMed1991

Calcium binding protein (calbindin-D28k) and glutamate decarboxylase gene expression after kindling induced seizures.

In order to determine whether calcium binding protein (calbindin-D28k or CaBP) and glutamate decarboxylase (GAD) may be involved in the process underlying the generation of seizure activity, changes in CaBP protein and mRNA and in GAD mRNA were examined in the kindling model of epilepsy. Following amygdaloid (AK) and commissure (CK) kindling significant decreases in the concentration of CaBP of 20% and 30%, respectively, were specifically observed in the hippocampal formation. However, using a cDNA specific to mammalian CaBP, Northern analysis of poly(A+) RNA and slot blot analysis of total RNA revealed no changes in the levels of CaBP mRNA in hippocampus, subcortical area (including amygdala, substantia nigra and striatum) or cerebellum of rats sacrificed 30 min, 1 h, 6 h or 24 h after the last kindled seizure. Similarly when these blots were reprobed with a cDNA specific to mammalian GAD, no changes in GAD gene expression were observed. However, fos gene expression was markedly enhanced at 1 h after seizure. We also tested whether changes in CaBP or GAD mRNA could be detected at any of the various stages of the kindling process. Slot blot analysis of cortex, subcortical structures and hippocampus revealed no changes in CaBP or GAD mRNA during the course of commissure kindling. In situ hybridization studies with GAD and CaBP 35S-labeled antisense probes also indicated no obvious changes upon visual analysis of autoradiographs. However, when silver grains were counted, significant changes in GAD mRNA in individual cells in hippocampus and substantia nigra were noted after kindling induced epilepsy. Our results indicate that, unlike fos gene expression, prominent alterations in GAD and CaBP mRNA in gross brain regions (as measured by slot blot and Northern blot analyses) are not observed in the kindling process. However, our in situ hybridization studies suggest that changes in GAD mRNA in individual cells may be involved in the process underlying kindling induced seizure activity.

Animals↗
PubMed1996

The effects of peripheral nerve injury of the masseteric nerve on the levels of calcium binding proteins and neuropeptide Y, and their correlation in the mesencephalic trigeminal nucleus of the rat.

Combined retrograde neuronal tracing with FluoroGold (FG) and a double immunofluorescence method was performed to examine the effects of peripheral nerve injury of the masseteric nerve (MassN) on the levels of two calcium binding proteins (CaBPs), parvalbumin (PV) and calbindin D28k (CB), and neuropeptide Y (NPY) in the mesencephalic trigeminal nucleus (MesV) in the rat. In the normal MesV, many medium- to large-sized unipolar PV-like immunoreactive (-IR) cells were detected through the entire rostrocaudal extent, but CB-IR cells were rarely observed. No NPY-IR cells were observed in the normal MesV. The distributions of these three neurochemical markers in the MesV contralateral to the transection of Mass were almost identical to those observed in the normal MesV. Four days following transection and application of FG to the MassN, approximately 52% (572/1104) and 38% (414/1104) of FG-labeled cells (FG cells) in the MesV displayed PV-like immunoreactivity (-LI) and NPY-LI, respectively; Approximately 24% (265/1104) of FG cells showed both PV-LI and NPY-LI. Approximately 47% (265/572) of FG cells with PV-LI showed NPY-LI or 64% (265/414) of FG cells with NPY-LI displayed PV-LI. Fourteen days following transection and application of FG, the percentage of FG cells with PV-LI significantly decreased to 36% (365/1024) compared to that observed 4 days post-injury; approximately 44% (448/1024) of FG cells displayed NPY-LI; approximately 38% (141/365) of FG cells with PV-LI showed NPY-LI and approximately 31% (141/448) of FG cells with NPY-LI displayed PV-LI. In contrast, FG cells showing CB-LI were very rare on 4 days (1%; 15/1182) or 14 days (1%; 16/1085) following MassN transection. The present results indicate that the levels of PV in the MesV decreased 14 days following the MassN injury compared to those observed 4 days post-injury and rapid induction of NPY in the injured MesV neurons, and that the correlation between CaBP and NPY in the MesV following the MassN transection is different from that observed in the trigeminal ganglion, which is equivalent to the MesV, following peripheral nerve injury of the inferior alveolar nerve.

Animals↗
PubMed1996

Calbindin-D28k-immunoreactivity in the trigeminal ganglion neurons and molar tooth pulp of the rat.

The cell body size and coexpression of carbonic anhydrase (CA), calretinin (CR) and calcitonin gene-related peptide (CGRP) of primary neurons with calbindin-D28k (CB) was examined in the trigeminal ganglion (TG) of the rat. CB-immunoreactive (-ir) cells were mostly large and preferentially distributed in the maxillary and mandibular divisions of the TG. 48% of CB-ir TG cells exhibited enzyme CA activity. 10% of CB-ir TG cells contained CR-ir. Most TG cells coexpressing CB- and CR-irs were localized to the maxillary and mandibular divisions and exhibited CA activity. 6.5% of CB-ir TG cells coexisted with CGRP-ir. 46% of TG cells coexpressing CB and CGRP exhibited CA activity. The innervation of the molar tooth pulp by CB-ir TG primary neurons was also examined. CB-ir thick and smooth nerve fibers projected from the root pulp to the pulp horn and the roof of the pulp chamber, where they became thinner and rarely entered the subodontoblastic layer. However, they could not be traced to the odontoblastic layer, predentin or dentine. The distribution pattern of CB-ir pulpal fibers was different from that of CR-ir ones. The trigeminal neurons cells retrogradely labeled with fast blue (FB) from the maxillary molar tooth pulp contained CB- and CR-irs. 23% and 1% of the labeled cells were immunoreactive for CB and CR, respectively. The coexpression of CB- and CR-immunoreactivities (-irs) in FB-labeled cells was negligible. An immunoelectron microscopic method revealed that 21% of pulpal nerve fibers were immunoreactive for CB, and that all CB-ir nerve fibers in the root pulp were myelinated. The present study indicated that the tooth pulp primary neurons contained CB-ir but did not coexpress CB- and CR-irs and that these neurons projected their myelinated axons to the pulp.

Animals↗
PubMed1995

Regulation of renal calbindin-D28K: the role of calcitonin.

Infusion of calcitonin lowers circulating calcium, but in the distal tubule of the kidney, pharmacological doses of calcitonin increase the active calcium reabsorption. Calbindin-D28k plays a significant role in the calcium reabsorption in the distal convoluted tubule of the kidney. The effect of calcitonin on renal calbindin-D28k in relation to calcium metabolic changes was therefore examined. In study 1, thyroparathyroidectomy followed by autotransplantation of the parathyroid glands (TX) was compared with a sham operation in rats. TX reduced plasma calcitonin from 54 +/- 2 to 9 +/- 1 pg/ml (P < 0.001), whereas ionized calcium and parathyroid hormone were returned to the control value after an initial decrease, indicating a successful implantation of the parathyroid glands. No changes were seen in calbindin-D or plasma 1,25(OH)2D. In study 2, subcutaneous infusion of salmon calcitonin 2.5 U/kg/hour via osmotic pumps was compared with infusion of vehicle in rats. Ionized calcium was reduced from 1.37 +/- 0.01 to 1.33 +/- 0.02 mmol/liter (P < 0.05), whereas no changes were seen in renal or intestinal calbindin-D or in plasma 1,25(OH)2D. After TX, only calcitonin decreased whereas the other calcium metabolic parameters showed no change. This indicates that in rats, selective elimination of calcitonin does not influence other parameters of the calcium metabolism and that the effect of calcitonin on calcium transport in the distal tubule is not mediated via an increase in renal calbindin-D28k.

Animals↗
PubMed2000

Early loss of interneurons and delayed subunit-specific changes in GABA(A)-receptor expression in a mouse model of mesial temporal lobe epilepsy.

Unilateral injection of kainic acid (KA) into the dorsal hippocampus of adult mice induces spontaneous recurrent partial seizures and replicates histopathological changes observed in human mesial temporal lobe epilepsy (MTLE) (Bouilleret V et al., Neuroscience 1999; 89:717-729). Alterations in pre- and postsynaptic components of GABAergic neurotransmission were investigated immunohistochemically at different time points (1-120 days) in this mouse model of MTLE. Markers of GABAergic interneurons (parvalbumin, calbindin-D28k, and calretinin), the type-1 GABA transporter (GAT1), and major GABA(A)-receptor subunits expressed in the hippocampal formation were analyzed. Acutely, KA injection produced a profound loss of hilar cells but only limited damage to CA1 and CA3 pyramidal cells. In addition, parvalbumin and calbindin-D28k staining of interneurons disappeared irreversibly in CA1 and dentate gyrus (DG), whereas calretinin staining was spared. The prominent GABA(A)-receptor alpha1 subunit staining of interneurons also disappeared after KA treatment, suggesting acute degeneration of these cells. Likewise, GAT1 immunoreactivity revealed degenerating terminals at 24 h post-KA in CA1 and DC and subsided almost completely thereafter. Loss of CA1 and, to a lesser extent, CA3 neurons became evident at 7-15 days post-KA. It was more accentuated after 1 month, accompanied by a corresponding reduction of GABA(A)-receptor staining. In contrast, DC granule cells were markedly enlarged and dispersed in the molecular layer and exhibited a prominent increase in GABA(A)-receptor subunit staining. After 4 months, the dorsal CA1 area was lost almost entirely, CA3 was reduced, and the DG represented most of the remaining dorsal hippocampal formation. No significant morphological alterations were detected contralaterally. These results suggest that loss of hilar cells and GABAergic neurons contributes to epileptogenesis in this model of MTLE. In contrast, long-term degeneration of pyramidal cells and granule cell dispersion may reflect distinct responses to recurrent seizures. Finally, GABA(A)-receptor upregulation in the DG may represent a compensatory response persisting for several months in epileptic mice.

Animals↗
PubMed1987

Evidence that low plasma 1,25-dihydroxyvitamin D causes intestinal malabsorption of calcium and phosphate in juvenile X-linked hypophosphatemic mice.

X-linked hypophosphatemic (Hyp) mice are a model for human sex-linked vitamin D-resistant rickets. We have reported intestinal malabsorption of calcium in young Hyp mice, and in this report we have explored the mechanism for it. To test for resistance of the intestine to 1,25(OH)2 vitamin D3, this hormone was continually infused via osmotic minipumps into 4-week-old normal and Hyp mice at 0, 17, 50 or 150 ng/kg/day. After 3 days, 45Ca and inorganic 32P were administered by gavage, and the mice were sacrificed on the fifth day. The Hyp mice showed responses to the hormone equivalent to the normal mice in terms of increased intestinal absorption of both 45Ca and 32P, increased plasma isotope levels, increased femoral isotope content, and increased duodenal and renal 9 kD vitamin D-dependent calcium-binding protein (calbindin-D9K; CaBP). Plasma 1,25(OH)2D was measured in these mice. There were significant correlations of plasma 1,25(OH)2D to the intestinal absorption of 45Ca and 32P and to duodenal and renal CaBP. Plasma 1,25(OH)2D was also measured in stock normal and Hyp mice and was found to be lower in 4-week-old Hyp mice than in 4-week-old normal mice (113 +/- 10 pM (n = 18) vs. 67 +/- 10 (n = 20), normal vs. Hyp, p less than .01), but unchanged at 13 weeks of age (77 +/- 13 (n = 13) vs. 70 +/- 15 (n = 15), NS). This observed difference in plasma 1,25(OH)2D between normal and Hyp mice at 4 weeks of age was sufficient to explain the observed normal-to-Hyp differences in intestinal absorption of 45Ca and duodenal and renal CaBP. It also explained 72 +/- 18% of the observed difference in 32P absorption. We conclude that Hyp mouse intestine is not resistant to 1,25(OH)2D and that the lower plasma 1,25(OH)2D of 4-week-old Hyp mice causes intestinal malabsorption of calcium and phosphate.

Animals↗
PubMed1998

Calbindin D28k-like immunoreactivity in the developing and regenerating circumvallate papilla of the rat.

The distribution of calbindin D28k (CB)-like immunoreactivity (-LI) in the circumvallate papilla (CVP) was examined during development and regeneration following bilateral crush injury to the glossopharyngeal nerve in the rat. In the adult CVP, CB-like immunoreactive (-IR) nerve fibers were observed in the subgemmal region and some penetrated into the taste buds. CB-LI was also detected in the cytoplasm of the spindle-shaped gustatory cells in the lower half of the trench epithelium, which contained numerous synaptic vesicles and bundles of intermediate filaments. These CB-IR gustatory cells made synapse-like contacts with CB-IR nerve terminals. Some CB-IR nerve terminals made contacts with the gustatory cells negative for CB-LI. At least three developmental stages were defined with regard to the developmental changes in the distribution of CB-LI: (1) Stage I (embryonic day (E) 18-postnatal day (P)5): CB-IR nerve fibers appeared in the lamina propria just beneath the newly-formed CVP at E18, but the gustatory epithelium of the CVP contained no CB-IR structures. Taste buds with taste pores appeared at P1. (2) Stage II (P5-10): thin CB-IR nerve fibers began entering the trench epithelium, but no CB-IR cells were observed. (3) Stage III (P10-adult): in addition to the intragemmal and perigemmal CB-IR nerve fibers, very few CB-IR cells appeared in the taste buds around P10, and their numbers increased progressively. The changes in the distribution of taste buds and CB-LI following glossopharyngeal nerve injury were similar to those observed during development. On post-operative day (PO) 4, the taste buds and CB-IR cells decreased markedly in number. These CB-IR cells became round in shape, and the number of CB-IR nerve fibers decreased markedly. On PO8, both taste buds and CB-IR cells disappeared completely. The regenerated taste buds were first observed on PO12, increased rapidly in number by PO20, and increased slowly thereafter. CB-IR nerve fibers accumulated at the subgemmal region and began penetrating into the trench wall epithelium around PO16. CB-IR cells appeared between PO20 and PO24, and their numbers increased progressively and reached the normal level on PO40. The topographical localizations of the taste buds and CB-IR cells during development and regeneration were comparable to those of normal animals. The delay of the time courses for appearance of CB-IR nerve fibers and CB-IR cells compared to the appearance of taste buds during development and regeneration suggests that CB in the gustatory epithelium may participate in the survival of the taste bud cells rather than in the induction of the taste buds.

Age Factors↗
PubMed2004

Characterisation of neurons expressing calbindin immunoreactivity in the ileum of the unweaned and mature sheep.

We have identified the enteric neuron types expressing immunoreactivity for the calcium-binding protein calbindin D28k (CALB) in cryostat sections and whole-mount preparations of myenteric (MP) and submucosal (SMP) plexuses of sheep ileum. We wished to determine whether CALB-IR in the sheep enteric nervous system was expressed in Dogiel type II cells, as in guinea-pig and rat ileum, and could therefore be used as a marker for intrinsic primary afferent neurons. The neurochemical coding of CALB-containing myenteric and submucosal neurons in ileum of unweaned lamb and mature sheep and its co-localisation with various neural markers was studied immunohistochemically. An antiserum against neuronal nuclear protein (NeuN) failed to detect the entire neuronal population; it was expressed only in 48% of neuron-specific enolase (NSE)-immunoreactive (NSE-IR) neurons. Human neuronal protein appeared to occur in the large majority or all neurons. Almost all CALB-IR neurons were: (1) radially multidendritic; (2) eccentric multidendritic; (3) Dogiel type II. CALB-IR occurred in 20-25% of myenteric and 65-75% of submucosal neurons in lamb and mature sheep, with higher values in mature sheep. Nearly all CALB-IR neurons were common choline acetyltransferase (cChAT)-IR, whereas only about 20% of cChAT-IR somata were CALB-IR. In lamb and mature sheep, 90% of MP CALB-IR neurons were peripheral choline acetyltransferase (pChAT)-IR. In lamb SMP, 80+/-13% of CALB-IR cells were also pChAT-IR, whereas all those in mature SMP were pChAT-IR. Fewer myenteric CALB-IR neurons exhibited tachykinin (TK) in mature sheep (49%) than in lamb (88%). This was also the case for submucosal ganglia (mature sheep, 63%; lamb, 89%). In lamb MP, 77+/-7% of CALB-IR cells were NeuN-positive. In mature sheep, 73+/-10% of CALB-IR somata were NeuN-IR, but NeuN failed to stain SMP neurons. In the MP of suckling and mature sheep, Dogiel type II CALB-IR neurons were calcitonin gene-related peptide (CGRP)-IR. In the SMP at both stages, Dogiel type II CALB-IR somata (about 50% of CALB-IR neurons) were also CGRP-IR. Only small proportions of CALB-IR neurons showed immunoreactivity for calretinin or nitric oxide synthase (NOS), although large populations of CALB and NOS neurons occurred in the ganglia. Thus, CALB is a marker of most Dogiel type II neurons in the sheep but is not confined to Dogiel II neurons. CGRP is a more selective marker of Dogiel type II neurons, being only found in this neuron type.

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PubMed1990

Ontological study of calbindin-D28k-like and parvalbumin-like immunoreactivities in rat spinal cord and dorsal root ganglia.

The calcium ion plays an important role in some critical developmental events in the nervous system, such as neurulation and neurite elongation. Therefore, as the intracellular calcium-binding proteins calbindin-D28k (CaB) and parvalbumin (PV) may be expressed in these developmental events. Accordingly, the ontological expression of CaB and PV was examined immunocytochemically in the spinal cord and dorsal root ganglia (DRG) of the rat, in order to evaluate the relationship between CaB and PV expression, and other important developmental events. During the ontogenesis of the spinal cord, the CaB-like immunoreactivity was mainly observed in the cell somata. The immunoreactive cells in the ventral horn of the cervical and thoracic, lumbar, and sacral segments first appeared at embryonic day (E)-12, E-13, and E-14, respectively. However, these cells were not detected in the intermediate gray matter of the same segments at E-14, E-15, and E-16, respectively, and in the dorsal horn at E-14-E-15, E-16, and E-17, respectively. The peak of immunoreactive cells, both as to number and intensity, occurred in the perinatal period. However, from postnatal day (P)-14 on, the number and intensity of the positive cells decreased, the adult levels being reached at P-35. The PV-like immunoreactivity was mainly detected in the fibers and punctata during the ontogenesis of the spinal cord. The immunoreactive fibers first appeared on the surface of the dorsal horn in the cervical and thoracic segments at E-14, then entered the dorsal horn at E-15, and reached the intermediate gray matter and ventral horn at E-16. The first appearance of these fibers in the same areas of the lumbar and sacral segments occurred 1 day later than in the cervical and thoracic segments. During the perinatal period, the maximum content of PV-like immunoreactive fibers, together with many punctata, was seen in the gray matter. However, between P-14 and P-17, most of them lost immunoreactivity rapidly, with the exception of the medial region of the intermediate gray matter, where the PV-immunoreactive punctata remained up to the adult stage. In DRG neurons, both CaB and PV was expressed, but in different neurons. Neurons labeled with anti-CaB and anti-PV sera were first detected at E-16 and E-14, respectively. These neurons were large or medium-sized in the prenatal period.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Vitamin D-dependent calcium binding protein in rat uterus: differential effects of estrogen, tamoxifen, progesterone, and pregnancy on accumulation and cellular localization.

The present studies were undertaken to characterize the expression of calcium binding protein (CaBP or calbindin-D9k) in uterine tissues. Using immunohistochemical techniques, calbindin-D9k was localized to the uterine (luminal) epithelium of pregnant rats, but not present in the uterine epithelium of nonpregnant rats. Calbindin was found also in the uterine smooth muscle and endometrial stromal cells of pregnant animals. These latter localizations were reproduced in uteri of 21-day-old nonpregnant rats by administration of tamoxifen or physiological doses of estrogens. Estrogen and tamoxifen produced half-maximal increases of uterine calbindin at daily doses of 0.1 and 10 micrograms, respectively, and maximal responses at 0.3 and 40 micrograms/day. Testosterone and progesterone, at doses which increased the growth of the uterus, did not induce calbindin-D, and both hormones blocked estradiol's effect on uterine calbindin-D appearance. The epithelial localization of calbindin in pregnant uteri was not reproduced in nonpregnant animals by either estradiol (3 micrograms/day) or progesterone (1 mg/day). The localization of calbindin in uterine epithelium during pregnancy appears to be dependent upon an as yet unknown factor. In view of the large surface area of the luminal epithelium in pregnant animals, and the pregnancy-related expression of calbindin in these cells, we propose that uterine epithelium plays an important role in transport of calcium during pregnancy.

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