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PubMed2000

Early brain injury in the SIV-macaque model of AIDS.

OBJECTIVE: To specify the type and severity of cellular damage in the central nervous system soon after infection and at later stages of disease in the SIV-macaque model of AIDS. DESIGN AND METHODS: Adjacent samples of frontal cortical gray matter were taken from three groups of macaques: uninfected controls (n = 4), acute (14 days post-infection; n = 4), and chronic (mean 2 years post-infection; n = 7). In vitro high resolution magnetic resonance spectroscopy of snap frozen intact tissue and quantitative neuropathology measurements of synaptophysin, calbindin, and glial fibrillary acidic protein (GFAP) in formalin-fixed tissue were performed. RESULTS: Losses in n-acetylaspartate and calbindin (indicating neuronal injury and/or death) and decreases in synaptophysin immunoreactivity (indicating synaptodendritic injury) were detected along with increases in GFAP (indicating reactive gliosis). Cellular injury worsened progressively with increased time after infection. CONCLUSIONS: These results are the first direct evidence that neuronal injury occurs soon after infection. The exacerbation of injury with time suggests a connection between the early response of the central nervous system and dementia, which occurs late in the course of infection. This connection may have broad implications for the study of and the development of therapies for damage of the central nervous system by HIV.

AIDS Dementia Complex↗
PubMed1998

Intracellular calcium parallels motoneuron degeneration in SOD-1 mutant mice.

Transgenic mice with Cu,Zn superoxide dismutase (SOD-1) mutations provide a unique model to examine altered Ca homeostasis in selectively vulnerable and resistant motoneurons. In degenerating spinal motoneurons of G93 A SOD-1 mice, developing vacuoles were filled with calcium, while calcium was gradually depleted from the cytoplasm and intact mitochondria. In oculomotor neurons, no degenerative changes, vacuolization, or increased calcium were noted. Motor axon terminals of interosseus muscle gradually degenerated and intracellular calcium was depleted. Oculomotor terminals of mutant SOD-1 mice were smaller and exhibited no degenerative changes, but did exhibit unique membrane-enclosed organelles containing calcium. Spinal motoneurons of SOD-1 mice were shown to have fewer calcium binding proteins, such as parvalbumin, compared with oculomotor neurons. These data suggest that the SOD-1 mutation is associated with impaired calcium homeostasis in motoneurons in vivo, with increased likelihood of degeneration associated with higher levels of intracellular calcium and lower to absent levels of calbindin-D28K and/or parvalbumin, and decreased likelihood of degeneration associated with minimally changed calcium and ample calbindin-D28K and/or parvalbumin.

Animals↗
PubMed1992

Survival of Purkinje Cells in Cerebellar Cultures is Increased by Insulin-like Growth Factor I.

Insulin-like growth factor I (IGF-I) is a trophic factor for both neurons and glia. Its presence in the developing and adult cerebellum suggests a role for this growth factor in this area of the brain. Recently, we have described the existence of an IGF-I-containing pathway in afferents of Purkinje neurons arising from the inferior olive. In addition, IGF-I receptors are present in the molecular layer of the cerebellar cortex. These observations prompted us to investigate whether the Purkinje cell is a target for IGF-I. Addition of IGF-I to rat cerebellar cultures produced a 7-fold increase in the number of Purkinje cells (calbindin-positive) together with an increase in the calbindin content of the cultures. IGF-I also doubled the number of surviving neurons and produced a moderate, non-significant increase in [3H]thymidine incorporation by the cultures. On the other hand, basic fibroblast growth factor (bFGF), which is also present in the cerebellum, produced a dramatic increase in both the proportion of astrocytes and in the mitotic activity of the cultures, without affecting neuron survival. We conclude that IGF-I is a specific promoter of Purkinje cell survival and that its effects differ from those produced by bFGF in fetal cerebellar cultures. These findings reinforce our hypothesis that the Purkinje cell is a target neuron for IGF-I action in the developing cerebellum.

Journal Article↗
PubMed1992

GABAergic Interneurons are the Major Postsynaptic Targets of Median Raphe Afferents in the Rat Dentate Gyrus.

The termination pattern of median raphe axons was studied in the rat dentate gyrus using Phaseolus vulgaris leucoagglutinin as an anterograde tracer, in combination with postembedding immunostaining for gamma-amino-butyric acid (GABA), and pre-embedding immunostaining for calbindin D28k, parvalbumin and GABA. Postembedding immunogold staining for GABA revealed that the majority (73.7%) of anterogradely labelled median raphe boutons make synaptic contacts with GABA-immunoreactive postsynaptic targets, mainly with dendritic shafts and perikarya. Pre-embedding immunocytochemical double staining for the anterograde tracer and GABA confirmed the electron microscopic results and showed that varicose median raphe axons establish multiple contacts with fusiform interneurons in the hilus and different types of basket cells in the granule cell layer. Some of the innervated cells were shown to contain calbindin D28k, whereas GABAergic interneurons containing another calcium-binding protein, parvalbumin, were never seen to receive multiple contacts from axons of raphe origin. Our results suggest that serotonergic median raphe fibres influence the firing of dentate granule cells via local inhibitory interneurons. The mechanism of using these interneurons with extensive local connections as monosynaptic targets may explain the great efficacy of this pathway in the control of hippocampal electrical activity.

Journal Article↗
PubMed2003

Ontogeny of the human amygdala.

Data on the fetal development of the human amygdala is reviewed with special reference to major ontogenetic events. In the fifth gestational month, the inferior portion of the amygdala reveals cell-dense columns merging with the ganglionic eminence (proliferative zone) in Nissl-stained sections. These columns contain vimentin-positive fibers and can therefore be regarded as migrational routes. In the sixth and seventh months, distinct reorganization of the cytoarchitectonics takes place. The sequential occurrence of afferens can be visualized using anti-GAP-43; moreover, outgrowing axons appear to reach the periphery of the ganglionic eminence. The latter may thus represent an intermediate target for growing axons using anti-calbindin and anti-calretinin. Migrating and immature amygdaloid neurons can be shown in the fifth month. From the eighth month onwards, various nonpyramidal neurons and pyramidal neurons are immunolabeled. Transient expression of calretinin in pyramidal neurons is observed. When punctate calbindin and calretinin immunostaining in the fifth and eighth months is compared, distinct redistribution is observed. On the whole, it is apparent that the amygdala has reached a high degree of maturity in the eighth month. At this developmental stage, AKAP79, being enriched in postsynaptic densities, shows a characteristic nuclear-specific distribution pattern. The latter largely corresponds to the expression pattern of NMDAR1. Thus, AKAP79 may have a preference for anchoring enzymes to glutamate receptors. The aforementioned results provide a basis for investigations on subtle changes in pathologically altered material, such as hemorrhage, in the ganglionic eminence of preterm infants.

Amygdala↗
PubMed2003

Regulation of the epithelial Ca2+ channels in small intestine as studied by quantitative mRNA detection.

The epithelial Ca2+ channels TRPV5 and TRPV6 are localized to the brush border membrane of intestinal cells and constitute the postulated rate-limiting entry step of active Ca2+ absorption. The aim of the present study was to investigate the hormonal regulation of these channels. To this end, the effect of 17beta-estradiol (17beta-E2), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and dietary Ca2+ on the expression of the duodenal Ca2+ transport proteins was investigated in vivo and analyzed using realtime quantitative PCR. Supplementation with 17beta-E2 increased duodenal gene expression of TRPV5 and TRPV6 but also calbindin-D9K and plasma membrane Ca2+-ATPase (PMCA1b) in ovariectomized rats. 25-Hydroxyvitamin D3-1alpha-hydroxylase (1alpha-OHase) knockout mice are characterized by hyperparathyroidism, rickets, hypocalcemia, and undetectable levels of 1,25(OH)2D3 and were used to study the 1,25(OH)2D3-dependency of the stimulatory effects of 17beta-E2. Treatment with 17beta-E2 upregulated mRNA levels of duodenal TRPV6 in these 1alpha-OHase knockout mice, which was accompanied by increased serum Ca2+ concentrations from 1.69 +/- 0.10 to 2.03 +/- 0.12 mM (P < 0.05). In addition, high dietary Ca2+ intake normalized serum Ca2+ in these mice and upregulated expression of genes encoding the duodenal Ca2+ transport proteins except for PMCA1b. Supplementation with 1,25(OH)2D3 resulted in increased expression of TRPV6, calbindin-D9K, and PMCA1b and normalization of serum Ca2+. Expression levels of duodenal TRPV5 mRNA are below detection limits in these 1alpha-OHase knockout mice, but supplementation with 1,25(OH)2D3 upregulated the expression to significant levels. In conclusion, TRPV5 and TRPV6 are regulated by 17beta-E2 and 1,25(OH)2D3, whereas dietary Ca2+ is positively involved in the regulation of TRPV6 only.

Animals↗
PubMed1998

Functional alterations in jejunal myenteric neurons during inflammation in nematode-infected guinea pigs.

Intracellular recordings of jejunal myenteric neurons with an afterspike hyperpolarization (AH) from Trichinella spiralis-infected animals showed enhanced excitability on days 3, 6, and 10 postinfection (PI) compared with uninfected animals. Lower membrane potential, increased membrane input resistance, decreased threshold for action potential discharge, decreased AH amplitude and duration, and increased fast excitatory postsynaptic potential amplitude and duration were characteristic of neuronal recordings from infected animals. Concurrent with electrophysiological changes during T. spiralis infection, increased cytochrome oxidase activity, a marker of neuronal metabolic activity, and the expression of nuclear c-Fos immunoreactivity, an indicator of transcriptional-translational activity, were also observed in myenteric ganglion cells. Double-labeling for calbindin-immunoreactive myenteric neurons revealed that approximately 50% of these neurons also expressed increased c-Fos immunoreactivity during T. spiralis infection. Myeloperoxidase activity was significantly higher in the jejunum of T. spiralis-infected guinea pigs on days 3, 6, and 10 PI vs. uninfected counterparts. The expression of c-Fos in calbindin-immunoreactive neurons together with enhanced neuronal electrical and metabolic activity during nematode-induced intestinal inflammation suggests the onset of excitation-transcription coupled changes in enteric neural microcircuits.

Action Potentials↗
PubMed2006

Expression of protein kinase C isoenzymes alpha, betaI, and delta in subtypes of intercalated cells of mouse kidney.

Recent studies of the distribution of PKC isoenzymes in the mouse kidney demonstrated that PKC-alpha, -beta(I), and -delta are expressed in intercalated cells. The purpose of this study was to identify the intercalated cell subtypes that express the different PKC isoenzymes and determine the location of the PKC isoenzymes within these cells. Adult C57BL/6 mice kidney tissues were processed for multiple-labeling immunohistochemistry. Antibodies against the vacuolar H(+)-ATPase and pendrin were used to identify intercalated cell subtypes, whereas antibodies against calbindin D(28K) and aquaporin-2 (AQP2) were used to identify connecting tubule cells and principal cells of the collecting duct, respectively. Within type A intercalated cells, PKC-delta was highly expressed in the apical part of the cells, whereas immunoreactivity for both PKC-alpha and PKC-beta(I) was weak. Type B intercalated cells exhibited strong expression of PKC-alpha, -beta(I), and -delta. PKC-alpha and -beta(I) were localized throughout the cytoplasm, whereas PKC-delta was restricted to the basal domain. Within non-A-non-B cells, immunoreactivity for both PKC-alpha and PKC-beta(I) was high in intensity and localized diffusely in the cytoplasm, whereas PKC-delta was localized in the apical part of the cells. None of the PKC isoenzymes (PKC-alpha, -beta(I), or -delta) were expressed in the calbindin D(28K)-positive connecting tubule cells. Within AQP2-positive principal cells of the collecting duct, PKC-alpha was expressed on the basolateral plasma membrane, but no significant staining was detected for PKC-beta(I) and -delta. In summary, this study demonstrates distinct and differential expression patterns of PKC-alpha, -beta(I), and -delta in the three subtypes of intercalated cells in the mouse kidney.

Animals↗
PubMed2003

Characterization of a murine renal distal convoluted tubule cell line for the study of transcellular calcium transport.

To unravel the molecular regulation of renal transcellular Ca(2+) transport, a murine distal convoluted tubule (mpkDCT) cell line derived from distal convoluted tubules (DCT) microdissected from a SV-PK/Tag transgenic mouse was characterized. This cell line originated from DCT only, as mRNA encoding for the DCT marker thiazide-sensitive Na(+)/Cl(-) cotransporter was expressed, whereas mRNA encoding for the connecting tubule and collecting duct marker aquaporin-2 was not detected, as determined by reverse-transcriptase PCR. mpkDCT cells expressed mRNA encoding the Ca(2+) channels TRPV5 and TRPV6 and other key players necessary for transcellular Ca(2+) transport, i.e., calbindin-D(9k), calbindin-D(28k), plasma membrane Ca(2+)-ATPase isoform 1b, and Na(+)/Ca(2+) exchanger 1. Primary cultures of DCT cells exhibited net transcellular Ca(2+) transport of 0.4 +/- 0.1 nmol.h(-1).cm(-2), whereas net transcellular Ca(2+) transport across mpkDCT cells was significantly higher at 2.4 +/- 0.4 nmol.h(-1).cm(-2). Transcellular Ca(2+) transport across mpkDCT cells was completely inhibited by ruthenium red, an inhibitor of TRPV5 and TRPV6, but not by the voltage-operated Ca(2+) channel inhibitors felodipine and verapamil. With the use of patch-clamp analysis, the IC(50) of ruthenium red on Na(+) currents was between the values measured for TRPV5- and TRPV6-expressing HEK 293 cells, suggesting that TRPV5 and/or TRPV6 is possibly active in mpkDCT cells. Forskolin in combination with IBMX, 1,25-dihydroxyvitamin D(3), and 1-deamino-8-d-arginine vasopressin increased transcellular Ca(2+) transport, whereas PMA and parathyroid hormone had no significant effect. In conclusion, the murine mpkDCT cell line provides a unique cell model in which to study the molecular regulation of transcellular Ca(2+) transport in the kidney in vitro.

Animals↗
PubMed1998

Organization of the caudal rhombencephalic alar plate of the ribbed newt Pleurodeles waltl: evidence for the presence of dorsal column and lateral cervical nuclei.

As part of a recent program on the evolution of somatosensory systems in vertebrates, the cytoarchitecture, chemoarchitecture, and fiber connections of the caudal rhombencephalic alar plate were studied in the ribbed newt, Pleurodeles waltl. This part of the brain stem includes ill-defined dorsal column and lateral cervical nuclei. A cytoarchitectonic analysis revealed that the caudal medullary alar plate consists of an inner and an outer cell layer. The dorsomedial part of the outer cell layer at the obex level contains the dorsal column nucleus (DCN), whereas its ventrolateral part constitutes the lateral cervical nucleus (LCN). NADPH-diaphorase histochemistry and calbindin D-28k immunohistochemistry clearly delineate the main components of the compact inner cell layer, i.e. the nucleus of the solitary tract dorsally and the nucleus of the descending trigeminal tract ventrally. Neither NADPH-diaphorase-labeled nor calbindin D-28k positive neurons were observed in the DCN and LCN. With anterograde and retrograde tracing, the DCN and LCN were further delineated. Labeling of ascending dorsal root projections showed that the dorsal column and the DCN are somatotopically arranged: lumbar primary afferent fibers terminate on medial DCN neurons, whereas cervical primary afferent fibers terminate on lateral DCN neurons. The LCN is densely innervated by the dorsolateral funiculus. Retrograde tracing showed extensive, predominantly contralateral projections of both the DCN and LCN to the torus semicircularis and the ventral thalamus. These data show that even in the poorly segregated caudal rhombencephalic alar plate of urodeles a DCN and LCN can be distinguished with afferent and efferent projections comparable to those in anurans and other terrestrial vertebrates.

Animals↗
PubMedDate not supplied

Neuronal differentiation of hippocampus-derived neural stem cells cultured in conditioned medium of embryonic rat retina.

PURPOSE: To investigate whether conditioned medium from embryonic rat retinas can induce differentiation of adult rat hippocampus-derived neural stem cells (AHSCs) into neurons and glia in vitro. METHODS: AHSCs were cultured in 3 types of media: standard culture medium, conditioned medium from embryonic rat retina, and standard culture medium with retinoic acid. Neuronal and glial differentiation of the cultured cells was assessed by cell growth analysis, flow cytometric analysis, immunofluorescent staining, and RT-PCR analysis. RESULTS: Cells cultured in the standard medium showed very little neuronal and glial differentiation. The cells cultured in the conditioned medium and the medium with retinoic acid showed neuronal morphology and growth inhibition. They also expressed mature neuronal markers and glial markers. In addition, the cells cultured in the conditioned medium expressed Thy-1, HPC-1, and calbindin, which were not found in the previous studies with postnatal retinas in vivo. Those cultured in the medium with retinoic acid expressed HPC-1 and calbindin, but not Thy-1. CONCLUSIONS: Conditioned medium from embryonic rat retina contains factors that induce neuronal and glial cell differentiation of AHSCs, and promote up-regulation of some types of retinal cell markers.

Animals↗
PubMed2003

Cortical orofacial motor representation in Old World monkeys, great apes, and humans. II. Stereologic analysis of chemoarchitecture.

This study presents a comparative stereologic investigation of neurofilament protein- and calcium-binding protein-immunoreactive neurons within the region of orofacial representation of primary motor cortex (Brodmann's area 4) in several catarrhine primate species (Macaca fascicularis, Papio anubis, Pongo pygmaeus, Gorilla gorilla, Pan troglodytes, and Homo sapiens). Results showed that the density of interneurons involved in vertical interlaminar processing (i.e., calbindin- and calretinin-immunoreactive neurons) as well pyramidal neurons that supply heavily-myelinated projections (i.e., neurofilament protein-immunoreactive neurons) are correlated with overall neuronal density, whereas interneurons making transcolumnar connections (i.e., parvalbumin-immunoreactive neurons) do not exhibit such a relationship. These results suggest that differential scaling rules apply to different neuronal subtypes depending on their functional role in cortical circuitry. For example, cortical columns across catarrhine species appear to involve a similar conserved network of intracolumnar inhibitory interconnections, as represented by the distribution of calbindin- and calretinin-immunoreactive neurons. The subpopulation of horizontally-oriented wide-arbor interneurons, on the other hand, increases in density relative to other interneuron subpopulations in large brains. Due to these scaling trends, the region of orofacial representation of primary motor cortex in great apes and humans is characterized by a greater proportion of neurons enriched in neurofilament protein and parvalbumin compared to the Old World monkeys examined. These modifications might contribute to the voluntary dexterous control of orofacial muscles in great ape and human communication.

Animal Communication↗
PubMed2005

Chemoarchitecture of the monotreme olfactory bulb.

The cyto- and chemoarchitecture of the olfactory bulb of two monotremes (shortbeaked echidna and platypus) was studied to determine if there are any chemoarchitectural differences from therian mammals. Nissl staining in conjunction with enzyme reactivity for NADPH diaphorase, and immunoreactivity for calcium binding proteins (parvalbumin, calbindin and calretinin), neuropeptide Y, tyrosine hydroxylase and non-phosphorylated neurofilament protein (SMI-32 antibody) were applied to the echidna. Material from platypus bulb was Nissl stained, immunoreacted for calretinin, or stained for NADPH diaphorase. In contrast to eutherians, no immunoreactivity for either the SMI-32 antibody or calretinin was found in the mitral or dispersed tufted cells of the monotremes and very few parvalbumin or calbindin immunoreactive neurons were found in the bulb of the echidna. On the other hand, immunoreactivity for tyrosine hydroxylase in the echidna was similar in distribution to that seen in therians, and periglomerular and granule cells showed similar patterns of calretinin immunoreactivity to eutherians. Multipolar neuropeptide Y immunoreactive neurons were confined to the deep granule cell layer and underlying white matter of the echidna bulb and NADPH diaphorase reactivity was found in occasional granule cells, fusiform and multipolar cells of the inner plexiform and granule cell layers, as well as underlying white matter. Unlike eutherians, no NPY immunoreactive or NADPH diaphorase reactive neurons were seen in the glomerular layer. The bulb of the echidna was comparable in volume to prosimians of similar body weight, and its constituent layers were highly folded. In conclusion, the monotreme olfactory bulb does not show any significant chemoarchitectural dissimilarities from eutheria, despite differences in mitral/tufted cell distribution.

Animals↗
PubMed2005

Glial remodeling and neural plasticity in human retinal detachment with proliferative vitreoretinopathy.

PURPOSE: To investigate glial remodeling and neuronal plasticity in adult human retinal detachment complicated by proliferative vitreoretinopathy (PVR) and to grade pathologic changes with a severity scoring system. METHODS: Sixteen full-thickness retinectomy specimens obtained at retinal relaxing surgery for PVR were fixed in 4% paraformaldehyde immediately after excision and compared to similarly processed normal donor retinas. Agarose-embedded sections (100-microm-thick) were double labeled for immunohistochemistry by confocal microscopy, with antibodies against rod opsin and GFAP; vimentin and M/L-cone opsin; calbindin D and S-cone opsin; and cytochrome oxidase and synaptophysin. These staining patterns formed the basis of a retinal pathology scoring system, and immunohistochemistry was also used to detect CD68, neurofilaments, protein kinase C, growth-associated protein-43, and a pan-cone-specific enzymatic marker. Morphology was also assessed by light microscopy of resin-embedded semithin sections. RESULTS: Prolonged detachment was characterized by photoreceptor degeneration and intracellular redistribution of opsin proteins to the plasma membrane in the outer nuclear layer (ONL). Remodeling of rod synaptic terminals was characterized by terminal retraction and also by axon extension to the inner retina in most specimens. Rod bipolar cell dendrites extended into the ONL, as did fine, horizontal cell processes. Large ganglion cells showed upregulated neurofilament and GAP-43 expression, with neurites sprouting from somata and axon collaterals. Anti-cytochrome oxidase labeling of surviving inner segments was reduced but detectable in all specimens, as was anti-calbindin D labeling of horizontal and amacrine cells. All specimens demonstrated a marked upregulation of Muller cell and astrocyte expression of GFAP and vimentin. More severe degenerative changes correlated with trauma and prolonged detachment duration when scored according to this system. CONCLUSIONS: The neural and glial components of detached neurosensory retina complicated by PVR exhibit pathology that changes characteristically with increasing detachment severity. Even in advanced degeneration, most of the structural motifs necessary for functional recovery are retained. Evidence of remodeling in the first-, second-, and third-order neurons of detached adult human retina may represent an attempt to re-establish synaptic connectivity.

Adolescent↗
PubMed2006

Long-term effects of a single adult methamphetamine challenge: minor impact on dopamine fibre density in limbic brain areas of gerbils.

BACKGROUND: The aim of the study was to test long-term effects of (+)-methamphetamine (MA) on the dopamine (DA) innervation in limbo-cortical regions of adult gerbils, in order to understand better the repair and neuroplasticity in disturbed limbic networks. METHODS: Male gerbils received a single high dose of either MA (25 mg/kg i.p.) or saline on postnatal day 180. On postnatal day 340 the density of immunoreactive DA fibres and calbindin and parvalbumin cells was quantified in the right hemisphere. RESULTS: No effects were found in the prefrontal cortex, olfactory tubercle and amygdala, whereas the pharmacological impact induced a slight but significant DA hyperinnervation in the nucleus accumbens. The cell densities of calbindin (CB) and parvalbumin (PV) positive neurons were additionally tested in the nucleus accumbens, but no significant effects were found. The present results contrast with the previously published long-term effects of early postnatal MA treatment that lead to a restraint of the maturation of DA fibres in the nucleus accumbens and prefrontal cortex and a concomitant overshoot innervation in the amygdala. CONCLUSION: We conclude that the morphogenetic properties of MA change during maturation and aging of gerbils, which may be due to physiological alterations of maturing vs. mature DA neurons innervating subcortical and cortical limbic areas. Our findings, together with results from other long-term studies, suggest that immature limbic structures are more vulnerable to persistent effects of a single MA intoxication; this might be relevant for the assessment of drug experience in adults vs. adolescents, and drug prevention programs.

Journal Article↗
PubMed2003

Chemically defined parallel pathways in the monkey auditory system.

The pathways ascending through the brain stem to the medial geniculate complex of the thalamus can be distinguished by immunostaining for the calcium binding proteins parvalbumin and calbindin and by the properties of the neurons in the subdivisions of the medial geniculate complex in which they terminate. The parvalbumin pathway, ascending from the central nucleus of the inferior colliculus, is the more direct and terminates in the ventral nucleus. The calbindin pathway is more diffuse in its origins and terminates in the dorsal and medial nuclei. Ventral nucleus neurons are sharply tuned, tonotopically organized and consistent in their responses. They project to core areas of the auditory cortex characterized by high parvalbumin immunoreactivity and by similar neuronal properties. Neurons in the dorsal and medial nuclei are not frequency specific or tonotopic and are labile in their responses. They project more diffusely to belt areas of the auditory cortex in which parvalbumin immunoreactivity is reduced and in which neuronal responses are less specific than in the core. The belt areas are the origins of streams of corticocortical connections leading into the temporal, parietal, and frontal lobes. These routes can be differentially engaged in functional imaging studies of monkeys responding to biologically significant sounds.

Animals↗
PubMed2002

Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of diabetic rats.

Maternal diabetes causes a range of complications in offspring, including reduced skeletal ossification. This study examined whether feeding gamma-linoleic acid (GLA) and ascorbate, alone or in combination, to diabetic pregnant rats improves skeletal development in their offspring. In addition, Ca(2+) concentration was monitored in maternal plasma and fetal tissue, as well as placental mRNA expression of calbindin-D(9k). Female rats rendered diabetic with streptozotocin were fed GLA (500 mg/kg/d), ascorbate (290 mg/kg/d), ascorbyl-GLA (790 mg/kg/d), or GLA and ascorbate (500 and 290 mg/kg/d, respectively) throughout pregnancy. Fetal skeletons were studied after alizarin red staining. Fewer ossification centers were observed in offspring of diabetic rats compared with offspring of control rats (68 +/- 4% of control, p = 0.01). An almost complete restoration of ossification occurred with all the treatments (92-95 +/- 3% of control). The effects of treatment on fetal ossification could not be explained by altered maternal plasma Ca(2+) concentrations or by mRNA expression of the placental Ca(2+)-transporting protein calbindin-D(9K). We conclude that GLA and/or ascorbate treatment was effective against diabetes-induced fetal ossification defects by a mechanism not related to placental Ca(2+) supply.

Animals↗
PubMed2004

Injectable dexamethasone administration enhances cortical GABAergic neuronal differentiation in a novel model of postnatal steroid therapy in mice.

Injectable dexamethasone (DXM) is widely used during the postnatal period in premature infants. However, this treatment has been associated with an increased incidence of neuromotor disorders. Few studies have directly addressed the impact of DXM therapy on neuronal differentiation. We used a murine model of postnatal steroid therapy in which mouse pups aged 3 and 4 postnatal days (P) received intraperitoneal injections of 1 mg . kg(-1) . 12 h(-1) of an injectable preparation that contained DXM and sulfites (DXM), pure DXM, or sulfites. The animals were weighed before they were killed on P5, P10, or P21, and their brains were investigated by immunohistochemistry with markers for neuronal differentiation. DXM administration was associated with a 20-30% reduction in body and brain weight gains and in cortical thickness on P5 and P10. gamma-Amino-butyric acid+ (GABA+) interneuron density was significantly increased (+50%) in the cerebral cortex of the animals given injectable DXM on P5 to P21 compared with controls (p < 0.01). In parallel, the density of cortical neurons expressing two interneuron markers (calbindin 28-kD and calretinin) increased significantly. These alterations occurred with injectable DXM but not with pure DXM or sulfites alone. In contrast, none of the study treatments modified the expression of other markers for neuronal transmission or axon myelination. In the animals that were given injectable DXM, cleaved caspase 3 antibody showed increased neuronal cell death, but calbindin antibody did not. In conclusion, in a murine model of postnatal steroid therapy, injectable DXM induced a selective increase in GABAergic neurons in the cerebral cortex.

Animals↗