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PubMed2003

Loss of calbindin-D28k from aging human cholinergic basal forebrain: relation to neuronal loss.

Cholinergic neurons of the basal forebrain (BFCN) are selectively vulnerable in neurodegenerative disorders of the elderly, particularly in Alzheimer's disease (AD). We investigated age-related changes in the BFCN that may serve as a substrate for this vulnerability. We report a substantial and selective age-related loss of the calcium binding protein calbindin-D(28K) (CB) from the human BFCN. Unbiased stereological estimation indicated that, in individuals under age 65 years, 72% of the choline acetyltransferase (ChAT)-positive BFCN contained CB immunoreactivity. In individuals over age 65 years, only 28% of the BFCN contained CB immunoreactivity, a dramatic loss of 61%. Similar results were obtained using neuronal counts from matching single- or double-stained sections in a larger cohort. The loss of CB immunoreactivity was neurochemically specific. No age-related changes were observed in the number of ChAT- or low-affinity nerve growth factor receptor (p75(NTR))-immunoreactive profiles. The loss of CB was greatest in very old individuals, in whom a small loss of BFCN was observed. Furthermore, the loss of CB displayed the same pattern as the loss of BFCN in AD and was more substantial in the posterior compared with the anterior BFCN sector, suggesting a role for CB in the selective vulnerability of BFCN in AD. The depletion of CB from the BFCN is likely to deprive these neurons of the capacity to buffer high levels of intracellular Ca(2+) and thus to leave them vulnerable to pathological processes, such as those in neurodegenerative disorders, which can cause increased intracellular Ca(2+), thus leading to their degeneration.

Adult↗
PubMed2003

Parvalbumin, calbindin, or calretinin in cortically projecting and GABAergic, cholinergic, or glutamatergic basal forebrain neurons of the rat.

The basal forebrain (BF) plays an important role in modulating cortical activity and facilitating processes of attention, learning, and memory. This role is subserved by cholinergic neurons but also requires the participation of other noncholinergic neurons. Noncholinergic neurons include gamma-amino butyric acidergic (GABAergic) neurons, some of which project in parallel with the cholinergic cells to the cerebral cortex, others of which project caudally or locally. With the original aim of distinguishing different subgroups of GABAergic neurons, we examined immunostaining for the calcium binding proteins (CBPs) parvalbumin (Parv), calbindin (Calb), and calretinin (Calret) in the rat. Although the CBP(+) cell groups were distributed in a coextensive manner with the GABAergic cells, they were collectively more numerous. Of cells retrogradely labeled with cholera toxin (CT) from the prefrontal or parietal cortex, Parv(+) and Calb(+) cells, but not Calret(+) cells, represented substantial proportions ( approximately 35-45% each) that collectively were greater than that of GABAergic projection neurons. From dual immunostaining for the CBPs and glutamic acid decarboxylase (GAD), it appeared that the vast majority (>90%) of the Parv(+) group was GAD(+), whereas only a small minority (<10%) of the Calb(+) or Calret(+) group was GAD(+). Significant proportions of Calb(+) (>40%) and Calret(+) (>80%) neurons were immunopositive for phosphate-activated glutaminase, the synthetic enzyme for transmitter glutamate. The results suggested that, whereas Calret(+) cells predominantly comprise caudally or locally projecting, possibly glutamatergic BF neurons, Parv(+) cells likely comprise the cortically projecting GABAergic BF neurons and Calb(+) cells the cortically projecting, possibly glutamatergic BF neurons that would collectively participate with the cholinergic cells in the modulation of cortical activity.

Acetylcholine↗
PubMed2003

Differential distribution of calbindin D28k and parvalbumin among functionally distinctive sets of structures in the macaque brainstem.

In a study of brainstem in the cynomolgus monkey, we found that the distribution of calbindin D28K (CB) and parvalbumin (PV) is nonoverlapping among functionally distinct sets of brainstem structures. Nuclei involved in representation and regulation of the organism's internal state contain CB, whereas those involved in the representation of the external environment and the representation or execution of externally directed actions contain only PV. Moreover, our findings indicate that different nuclei known as components of the ascending reticular activating system (ARAS) contain either CB or PV or both, suggesting that this system in primates operates with both CB and PV. In line with previously reported findings, we also found that unmyelinated pathways contain only CB, whereas myelinated pathways contain PV. Distribution of CB and PV in the macaque brainstem follows a pattern comparable to, but in some instances significantly different than, the pattern previously reported in the rat. We argue that the nonoverlapping distribution of CB and PV among different structures of the brainstem might reflect underlying differences in the physiological, anatomic, and perhaps phylogenetic properties of these structures. Considering our recent findings of selective vulnerability of brainstem structures to Alzheimer's disease, the present data suggest that the majority of macaque brainstem nuclei that contain CB are vulnerable to neurofibrillary tangles in humans. By contrast, only few nuclei that contain PV exhibit pathologic changes. Some of these nuclei are affected with a high number of neuritic plaques without ever developing neurofibrillary tangles.

Animals↗
PubMed2003

Complementary distribution of vesicular glutamate transporters 1 and 2 in the nucleus accumbens of rat: Relationship to calretinin-containing extrinsic innervation and calbindin-immunoreactive neurons.

The caudomedial shell of the rat nucleus accumbens exhibits inhomogeneous distribution patterns of the vesicular glutamate transporters 1 (VGLUT1) and 2 (VGLUT2). This paper focuses on the question of whether patterns of VGLUT1 and VGLUT2 correspond to cytoarchitectonically and cytochemically defined subterritories of the caudomedial shell region. VGLUT2 was shown to be coexpressed with calretinin in the dense axonal plexus known to emanate from the paraventricular thalamic nucleus. In regions termed corridors, which are spared by this paraventricular thalamic innervation, axonal terminals were found to be clustered and VGLUT1-immunoreactive. It is assumed that these fibers originate in the prelimbic cortex and/or in the parvicellular basal amygdaloid nucleus known to project to accumbal shell components. Our findings confirm the existence of two well-separated neuronal circuits in the caudomedial shell that are dominated by two different excitatory input systems originating from either thalamic, cortical, or cortex-like amygdaloid sources. The large lateral corridors-which resemble the accumbal core not only in respect to their VGLUT1 immunolabeling but also concerning their content of calbindin-positive cells-may represent a component of the anatomically weakly defined accumbal shore region.

Afferent Pathways↗
PubMed2006

Immunohistochemical localization of calbindin-D28k and calretinin in the spinal cord of Xenopus laevis.

Immunohistochemical techniques were used to investigate the distribution and morphology of neurons containing the calcium-binding proteins calbindin-D28k (CB) and calretinin (CR) in the spinal cord of Xenopus laevis and determine the extent to which this organization is comparable to that of mammals. Most CB- and CR-containing neurons were located in the superficial dorsal gray field, but with distinct topography. The lateral, ventrolateral, and ventromedial fields also possessed abundant neurons labeled for either CB or CR. Double immunohistofluorescence demonstrated that a subpopulation of dorsal root ganglion cells and neurons in the dorsal and ventrolateral fields contained CB and CR. By means of a similar technique, a cell population in the dorsal field was doubly labeled only for CB and nitric oxide synthase (NOS), whereas in the ventrolateral field colocalization of NOS with CB and CR was found. Choline acetyltransferase immunohistochemistry revealed that a subpopulation of ventral horn neurons, including motoneurons, colocalized CB and CR. The involvement of CB- and CR-containing neurons in ascending spinal projections was demonstrated combining the retrograde transport of dextran amines and immunohistochemistry. Cells colocalizing the tracer and CB or CR were quite numerous, primarily in the dorsal and ventrolateral fields. Similar experiments demonstrated supraspinal projections from CB- and CR-containing cells in the brainstem and diencephalon. The distribution, projections, and colocalization with neurotransmitters of the neuronal systems containing CB and CR in Xenopus suggest that CB and CR are important neuromodulator substances with functions conserved in the spinal cord from amphibians through mammals.

Animals↗
PubMed1989

Calcium-binding protein (calbindin-D28k) and parvalbumin immunocytochemistry: localization in the rat hippocampus with specific reference to the selective vulnerability of hippocampal neurons to seizure activity.

Two neuronal calcium-binding proteins, calbindin-D28k (CaBP) and parvalbumin (PV), were localized in the normal rat hippocampus by using immunocytochemical methods to determine 1) their location and 2) whether a correlation exists between the presence of these two calcium-binding proteins and the selective vulnerability of different hippocampal neuronal populations to experimental seizure activity. CaBP-like immunoreactivity (CaBP-LI) is present in all dentate granule cells and some, but not all, CA1 and CA2 pyramidal cells. Some CA1 pyramidal cells lack CaBP-LI, and those that do are lightly stained compared to the dentate granule cells. CA3 pyramidal cells appear to contain neither CaBP- nor PV-LI, and no granule or pyramidal cells exhibit PV-LI. CaBP-LI is present in distinct populations of dentate and hippocampal interneurons but absent from others. In area dentata, CaBP-LI is present in a small number of interneurons of the molecular and granule cell layers and in a small population of presumed basket cells in or below the granule cell layer. Conversely, more presumed dentate basket cells exhibit PV-LI than CaBP-LI. In the hilus of area dentata, few cells are CaBP- or PV-immunoreactive. The hilar somatostatin/neuropeptide Y (NPY)-immunoreactive cells and hilar mossy cells, two distinct and large populations, lack CaBP- and PV-LI. In the CA3 region, CaBP-LI is present in a relatively small number of interneurons in each stratum. PV-immunoreactive interneurons in area CA3 are more numerous. In area CA1, CaBP-LI is present in many interneurons in strata radiatum and lacunosum-moleculare. Some, but relatively fewer, CaBP-positive interneurons are present in strata pyramidale and oriens. Conversely, PV-immunoreactive interneurons are numerous in strata pyramidale and oriens but rare in strata radiatum and lacunosum-moleculare. Staining with the particulate chromagen benzidine hydrochloride revealed a previously undescribed dense band of CaBP-LI in the inner dentate molecular layer, a lamina enriched with kainate-displaceable glutamate-binding sites and innervated by the apparently excitatory ipsilateral associational/commissural (IAC) pathway that originates in the CaBP-negative hilar mossy cells. Bilateral electrical stimulation of the perforant path was performed in order to destroy the hilar mossy cells and to determine if this band of CaBP-LI is normally present within the mossy cell terminals. Perforant path stimulation that destroyed hilar mossy cells throughout the dorsal portions of both hippocampi did not abolish the dense CaBP-like immunoreactivity in the inner molecular layer.

Animals↗
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↗
PubMed1991

Calcium-binding protein (calbindin-D28K) and parvalbumin immunocytochemistry in the normal and epileptic human hippocampus.

The calcium-binding proteins calbindin-D28K (CaBP) and parvalbumin (PV) were localized in the "normal" and "epileptic" human hippocampus to address the possible relationship between the expression of these constitutive cytosolic calcium-binding proteins and the resistance or selective vulnerability of different hippocampal neuron populations in temporal lobe epilepsy. Compared to rodents and a baboon (Papio papio), the pattern of CaBP-like immunoreactivity (LI) in the "normal" human hippocampus is unique. CaBP-LI is present in the dentate granule cells, neurons of the "resistant zone" (area CA2), and presumed interneurons of all regions. Unlike rodent and baboon CA1 pyramidal cells, human CA1 pyramidal cells appear to be devoid of CaBP-LI. Thus, the relatively resistant dentate granule cells and CA2 pyramidal cells are the only human hippocampal principal cells that contain CaBP-LI normally. As in lower mammals, PV-LI is present exclusively in interneurons of all human hippocampal subregions. CaBP- and PV-LI were localized in hippocampi surgically removed in the treatment of intractable temporal lobe epilepsy to determine whether surviving hippocampal cells were those that express these calcium-binding proteins. Hippocampi removed from patients with tumors or arteriovenous malformations that were associated with complex partial seizures arising from this region appeared relatively normal histologically. CaBP- and PV-LI in this patient group appeared similar to that seen in autopsy controls. Conversely, "cryptogenic" epileptics, who exhibit hippocampal sclerosis as the only lesion associated with the epilepsy, exhibited a preferential survival of hippocampal cells that were CaBP- or PV-immunoreactive. In the dentate hilus, which normally contains few CaBP-LI neurons, most of the few surviving hilar neurons were CaBP-immunoreactive. Their number and darkness of staining suggests that CaBP synthesis may be increased in cells that survive. Despite an obvious decrease of PV-LI specifically in the damaged parts of the sclerotic hippocampi, PV-immunoreactive interneurons were often among the few surviving cells. Nevertheless, large expanses of the surviving granule cell layer appeared to have lost the PV-immunoreactive axosomatic fiber plexus. These results reveal a unique and striking correlation between the human hippocampal cells that normally express these calcium-binding proteins and those that survive in the sclerotic epileptic hippocampus.

Adult↗
PubMed1991

Different populations of parvalbumin- and calbindin-D28k-immunoreactive neurons contain GABA and accumulate 3H-D-aspartate in the dorsal horn of the rat spinal cord.

The colocalization of parvalbumin (PV), calbindin-D28k (CaBP), GABA immunoreactivities, and the ability to accumulate 3H-D-aspartate selectively were investigated in neurons of laminae I-IV of the dorsal horn of the rat spinal cord. Following injection of 3H-D-aspartate into the basal dorsal horn (laminae IV-VI), perikarya selectively accumulating 3H-D-aspartate were detected in araldite embedded semithin sections by autoradiography, and consecutive semithin sections were treated to reveal PV, CaBP and GABA by postembedding immunocytochemistry. Perikarya accumulating 3H-D-aspartate were found exclusively in laminae I-III, and no labelled somata were found in deeper layers or in the intermediolateral column although the labelled amino acid clearly spread to these regions. More than half of the labelled cells were localized in lamina II. In this layer, 16.4% of 3H-D-aspartate-labelled perikarya were also stained for CaBP. In contrast to CaBP, PV or GABA was never detected in neurons accumulating 3H-D-aspartate. A high proportion of PV-immunoreactive perikarya were also stained for GABA in laminae II and III (70.0% and 61.2% respectively). However, the majority of CaBP-immunoreactive perikarya were GABA-negative. GABA-immunoreactivity was found in less than 2% of the total population of cells stained for CaBP in laminae I-IV. A significant proportion of the GABA-negative but PV-immunoreactive neurons also showed CaBP-immunoreactivity in laminae II and IV. These results show that out of the two calcium-binding proteins, CaBP is a characteristic protein of a small subpopulation of neurons using excitatory amino acids and PV is a characteristic protein of a subpopulation of neurons utilizing GABA as a transmitter. However, both proteins are present in additional subgroups of neurons, and neuronal populations using inhibitory or excitatory amino acid transmitters are heterogeneous with regard to their content of calcium-binding proteins in the dorsal horn of the rat spinal cord.

Animals↗
PubMed1991

GABAergic interneurons containing calbindin D28K or somatostatin are major targets of GABAergic basal forebrain afferents in the rat neocortex.

The arborization pattern and postsynaptic targets of the GABAergic component of the basal forebrain projection to neo- and mesocortical areas have been studied by the combination of anterograde tracing and pre- and postembedding immunocytochemistry. Phaseolus vulgaris leucoagglutinin (PHAL) was iontophoretically delivered into the region of the diagonal band of Broca, with some spread of the tracer into the substantia innominata and ventral pallidum. A large number of anterogradely labelled varicose fibres were visualized in the cingulate and retrosplenial cortices, and a relatively sparse innervation was observed in frontal and occipital cortical areas. Most of the labelled axons were studded with large en passant varicosities (Type 1), whereas the others (Type 2) had smaller boutons often of the drumstick type. Type 1 axons were distributed in all layers of the mesocortex with slightly lower frequency in layers 1 and 4. In the neocortex, layer 4, and to a smaller extent upper layer 5 and layer 6 contained the largest number of labelled fibres, whereas only a few fibres were seen in the supragranular layers. Characteristic type 2 axons were very sparse but could be found in all layers. Most if not all boutons of PHAL-labelled type 1 axons were shown to be GABA-immunoreactive by immunogold staining for GABA. Altogether 73 boutons were serially sectioned and found to make symmetrical synaptic contacts mostly with dendritic shafts (66, 90% of total targets), cell bodies (6, 8.2% of total), and with one spine. All postsynaptic cell bodies, and the majority of the dendritic shafts (44, 60.3% of total targets) were immunoreactive for GABA. Thus at least 68.5% of the total targets were GABA-positive, but the majority of the dendrites not characterized immunocytochemically for technical reasons (15.1%) also showed the fine structural characteristics of nonpyramidal neurons. The target interneurons included some of the somatostatin- and calbindin-containing subpopulations, and a small number of parvalbumin-containing neurons, as shown by double immunostaining for PHAL and calcium-binding proteins or neuropeptides. We suggest that the innervation of inhibitory interneurons having extensive local axon arborizations may be a mechanism by which basal forebrain neurons-most notably those containing GABA--have a powerful global effect on the majority of principal cells in the entire cortical mantle.

Afferent Pathways↗
PubMed1993

Transient appearance of calbindin-D28k-positive neurons in the superior olivary complex of developing rats.

Calbindin-D28k (CaBP) is a calcium-binding protein that is prominent in various parts of the mammalian auditory system. In order to shed some light on the possible role of CaBP during ontogeny, when calcium ions play key roles in several processes, the location of CaBP was examined immunocytochemically in the auditory system of the developing rat. This study focuses on the principal nuclei of the superior olivary complex, which show distinct CaBP labeling in the adult. Consistent with previous reports in the rat and other mammals, CaBP immunoreactivity in adults was intense in somata of the medial nucleus of the trapezoid body (MNTB) and in the neuropil (presumably in axons) of the lateral superior olive (LSO), the superior paraolivary nucleus (SPN), and the medial superior olive (MSO). In fetal and neonatal animals, however, the labeling pattern was strikingly different. Around birth, MNTB neurons are immunonegative for CaBP, whereas somata and processes in the LSO, probably neuronal, are heavily labeled at that age. This labeling pattern persists throughout the first week of postnatal life and begins to change at P8, when MNTB neurons become immunopositive for CaBP. During the next 10 days labeling intensity in MNTB neurons increases considerably, and the increase is paralleled by an increase in labeling intensity of the neuropil in the LSO, SPN, and MSO, indicating that the labeled processes in these nuclei may be axons originating from MNTB neurons. Immunoreactivity in LSO cells begins to decline around P8, decays rapidly between P10 and P18, and reaches its adult level around P28, when the CaBP labeling pattern in the whole superior olivary complex is indistinguishable from that in the adult. The present results show that the development of CaBP immunoreactivity in the rat superior olivary complex is characterized by two reciprocally related processes: as immunoreactivity within MNTB somata and fibers in the SPN, and LSO, and the MSO increases between P8 and about P21, the immunoreactivity in LSO neurons declines. CaBP immunoreactivity in LSO neurons is only transiently present, suggesting a critical period in development during which the control of Ca2+ homeostasis in LSO neurons may be of particular importance.

Animals↗
PubMed1993

Distribution, morphological features, and synaptic connections of parvalbumin- and calbindin D28k-immunoreactive neurons in the human hippocampal formation.

Calcium binding proteins calbindin D28k (CaBP) and parvalbumin (PV) are known to form distinct subpopulations of gamma-aminobutyric acid (GABA)ergic neurons in the rodent hippocampal formation. Light and electron microscopic morphology and connections of these protein-containing neurons are only partly known in the primate hippocampus. In this study, CaBP and PV were localized in neurons of the human hippocampal formation including the subicular complex (prosubiculum, subiculum, and presubiculum) in order to explore to what extent these subpopulations of hippocampal neurons differ in phylogenetically distant species. CaBP immunoreactivity was present in virtually all granule cells of the dentate gyrus and population of in a proportion of pyramidal neurons in the CA1 and CA2 regions. A distinct population of CaBP-positive local circuit neurons was found in all layers of the dentate gyrus and Ammon's horn. Most frequently they were located in the molecular layer of the dentate gyrus and the pyramidal layer of Ammon's horn. In the subicular complex pyramidal neurons were not immunoreactive for CaBP. In the prosubiculum and subiculum immunoreactive nonpyramidal neurons were equally distributed in all layers, whereas in the presubiculum they occurred mainly in the superficial layers. Electron microscopy showed typical somatic and dendritic features of the granule, pyramidal, and local circuit neurons. CaBP-positive mossy fiber terminals in the hilus of the dentate gyrus and terminals of presumed pyramidal neurons of Ammon's horn formed asymmetric synapses with dendrites and spines. CaBP-positive terminals of nonprincipal neurons formed symmetric synapses with dendrites and dendritic spines, but never with somata or axon initial segments. PV was exclusively present in local circuit neurons in both the hippocampal formation and subicular complex. Most of the PV-positive cell bodies were located among or close to the principal cell layers. However, large numbers of immunoreactive neurons were also found in the molecular layer of the dentate gyrus and in strata oriens of Ammon's horn. PV-positive cells were equally distributed in all layers of the subicular complex. Electron microscopy showed the characteristic somatic and dendritic features of local circuit neurons. PV-positive axon terminals formed exclusively symmetric synapses with somata, axon initial segments and dendritic shafts, and in a few cases with dendritic spines. The CaBP- and PV-containing neurons formed similar subpopulations in rodents, monkeys, and humans, although the human hippocampus displayed the largest variability of these immunoreactive neurons in their morphology and location. Calcium binding protein-containing neurons frequently occurred in the molecular layer of the human dentate gyrus and in the stratum lacunosum-moleculare of Ammon's horn.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1994

Distribution of calcium-binding protein calbindin-D28k in the auditory system of adult and developing rats.

Calbindin-D28k (CaBP) is a calcium-binding protein, which appears to be involved in the buffering of free intracellular calcium and may thereby contribute to calcium homeostasis. This study attempted to determine the distribution pattern of CaBP immunoreactivity in the central auditory system of adult rats and during development, when calcium ions play key roles in several aspects of nerve cell function. It was found that most steps during CaBP development occur postnatally in the central auditory system. With the exception of the lateral superior olive, the ventral and the intermediate nuclei of the lateral lemniscus, and the auditory cortex, which already express CaBP prenatally, CaBP immunoreactivity is not present before postnatal day 2 (P2). Development proceeds until about P24, when the pattern characteristic of adult animals can be seen. There was no detectable sequence in CaBP development from lower to higher stations in the auditory pathway, i.e., the different nuclei appear to express CaBP independently of each other, indicating that intrinsic, rather than peripheral, maturation processes may predominantly influence CaBP expression. Neurons in four brainstem nuclei (the lateral superior olive, the ventral and intermediate nuclei of the lateral lemniscus, and the central nucleus of the inferior colliculus) express CaBP only transiently. In these nuclei, CaBP immunoreactivity peaks between P6 and P18, which coincides with the period of synapse stabilization. Therefore, CaBP may play a specific role during neuronal development, by buffering the concentration of intracellular free Ca2+, which may be necessary for modification of synaptic efficiency.

Animals↗
PubMed2004

Calbindin D28k, parvalbumin, and calretinin immunoreactivity in the main and accessory olfactory bulbs of the gray short-tailed opossum, Monodelphis domestica.

The vertebrate main and accessory olfactory bulbs (MOB and AOB) are the first synaptic sites in the olfactory pathways. The MOB is a cortical structure phylogenetically well conserved in its laminar structure and overall synaptic organization, while the AOB has significant species variation in size. In order to better understand signal processing in the two olfactory systems and the species differences, immunocytochemical staining and analysis were done of the neuronal expression patterns of the calcium-binding proteins calbindin D28k (CB), parvalbumin (PV), and calretinin (CR) in the MOB and AOB in a marsupial species, the gray short-tailed opossum, Monodelphis domestica. In the MOB, antibody to CB labeled periglomerular cells, superficial short axon cells / Van Gehuchten cells; antibody to PV labeled Van Gehuchten cells; and antibody to CR immunostained periglomerular cells, superficial short axon cells / Van Gehuchten cells, and granule cells. In the AOB, CB immunoreactivity was detected in periglomerular cells and a subpopulation of granule cells; antibody to PV labeled the superficial short axon cells / Van Gehuchten cells and granule cells; and antibody to CR labeled a small number of periglomerular cells, superficial short axon cells / Van Gehuchten cells, and granule cells. These results showed that the patterns of CB, PV, and CR expression differ in the opossum main and accessory olfactory bulbs and differ from that in other animal species. These varying patterns of neuronal immunostaining may be related to the different functions of the main and accessory olfactory bulbs and to the differing signal processing features.

Animals↗
PubMed1990

Lurcher Purkinje cells express glutamic acid decarboxylase and calbindin mRNAs.

Purkinje neurons in immature Lurcher (Lc/+) mice are destined to die as a result of a defect intrinsic to the dying cells. We have used in situ hybridization to determine whether the Lc allele interferes with the normal program of gene expression in the doomed Purkinje cells. In P21 mice, degeneration of Purkinje cells is well underway, but the surviving Purkinje cells continue to express the mRNAs for both glutamate decarboxylase and calbindin D28K, two proteins whose expression is characteristic of normal Purkinje neurons. We conclude that the Lc allele probably does not interfere with the developmental program but acts to cause cell death in already differentiated Purkinje neurons.

Alleles↗
PubMed1991

Bursting response to current-evoked depolarization in rat CA1 pyramidal neurons is correlated with lucifer yellow dye coupling but not with the presence of calbindin-D28k.

Calbindin-D28k (CaBP) immunohistochemistry has been combined with electrophysiological recording and Lucifer Yellow (LY) cell identification in the CA1 region of the rat hippocampal formation. CaBP is shown to be contained within a distinct sub-population of CA1 pyramidal cells which is equivalent to the superficial layer described by Lorente de Nó (1934). The neurogenesis of these CaBP-positive neurons occurs 1-2 days later than the CaBP-negative neurons in the deep pyramidal cell layer, as shown by 3H-thymidine autoradiography. No correlation could be found between the presence or absence of CaBP and the type of electrophysiological response to current-evoked depolarizing pulses. The latter could be separated into bursting or non-bursting types, and the bursting-type response was nearly always found to be associated with the presence of LY dye coupling. Furthermore, when dye coupling involved three neurons, a characteristic pattern was observed which may represent the coupling of phenotypically identical neurons into distinct functional units within the CA1 pyramidal cell layer. In this particular case the three neurons were all likely to be CaBP-positive.

Animals↗
PubMed1998

Quantitative distribution of parvalbumin, calretinin, and calbindin D-28k immunoreactive neurons in the visual cortex of normal and Alzheimer cases.

The distribution of parvalbumin (PV), calretinin (CR), and calbindin (CB) immunoreactive neurons was studied with the help of an image analysis system (Vidas/Zeiss) in the primary visual area 17 and associative area 18 (Brodmann) of Alzheimer and control brains. In neither of these areas was there a significant difference between Alzheimer and control groups in the mean number of PV, CR, or CB immunoreactive neuronal profiles, counted in a cortical column going from pia to white matter. Significant differences in the mean densities (numbers per square millimeter of cortex) of PV, CR, and CB immunoreactive neuronal profiles were not observed either between groups or areas, but only between superficial, middle, and deep layers within areas 17 and 18. The optical density of the immunoreactive neuropil was also similar in Alzheimer and controls, correlating with the numerical density of immunoreactive profiles in superficial, middle, and deep layers. The frequency distribution of neuronal areas indicated significant differences between PV, CR, and CB immunoreactive neuronal profiles in both areas 17 and 18, with more large PV than CR and CB positive profiles. There were also significantly more small and less large PV and CR immunoreactive neuronal profiles in Alzheimer than in controls. Our data show that, although the brain pathology is moderate to severe, there is no prominent decrease of PV, CR and CB positive neurons in the visual cortex of Alzheimer brains, but only selective changes in neuronal perikarya.

Aged↗
PubMed1999

The effect of a peripheral nerve lesion on calbindin D28k immunoreactivity in the cervical ventral horn of developing and adult rats.

Expression of calbindin D28k (CB) immunoreactivity by putative Renshaw cells is substantially downregulated by sciatic motoneuron axotomy in the adult rat. The present study investigated the effect of median and ulnar nerve lesion at different ages on ventral horn CB immunoreactivity 7 days after the injury to see whether similar results were obtained in the cervical cord and during development. Two major differences were observed. First, axotomy induced CB immunoreactivity in some motoneurons, confirmed by retrograde labeling of the injured neurons with fast blue (FB). Observation of fluorescent phagocytic microglia revealed that some motoneuron death occurred following lesions at postnatal day 2 (P2) and P7, but not at P21 or P63. A significantly higher proportion of remaining FB labeled motoneurons expressed CB following lesion at P2 (mean 33% +/- 7.6 SD) and P7 (30.6% +/- 5.2) than at P28 (14.0% +/- 1.9). Second, CB expression by putative Renshaw cells was not significantly downregulated ipsilateral to the lesion. CB immunofluorescent putative Renshaw cells were counted in sections containing FB labeled motoneurons. No consistent differences in the numbers of Renshaw cells ipsilateral and contralateral to the lesion were found at any age. To confirm that these neurons really were Renshaw cells, the mediators of recurrent inhibition to cholinergic motoneurons, we employed double-immunofluorescence labeling with confocal microscopy. The group of CB immunopositive neurons located among the converging ventral roots in the cervical cord were closely apposed by many axon terminals immunoreactive for (i) vesicular acetylcholine transporter and (ii) cholera toxin B localized to motor axon collaterals by injection of this tracer into a distal forelimb muscle. We conclude that motoneuron axotomy need not always downregulate CB expression in associated Renshaw cells. In addition, some brachial motoneurons respond to axotomy by expressing CB.

Aging↗