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Gene Review

Calb1  -  calbindin 1

Rattus norvegicus

Synonyms: Calbindin, Calbindin D28, D-28K, Spot 35 protein, Vitamin D-dependent calcium-binding protein, avian-type
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Disease relevance of Calb1

  • Expression in Escherichia coli of full-length and mutant rat brain calbindin D28. Comparison with the purified native protein [1].
  • 1. We have examined the ability of the Ca(2+)-binding proteins (CABP) calbindin D28k and paravalbumin to modulate increases in the intracellular free Ca2+ concentration ([Ca2+]i), produced by brief depolarizations, in rat dorsal root ganglion (DRG) neurones [2].
  • We used herpes simplex amplicons to overexpress calbindin D(28k) (CaBP) selectively in dentate gyrus (DG) granule cells [3].
  • Immunoreactive staining for the calcium-binding proteins calbindin and parvalbumin in lower brainstem auditory nuclei shows abnormalities in areas susceptible to the effects of hyperbilirubinemia and provides a sensitive new way to assess bilirubin toxicity in the auditory system [4].
  • Nonetheless, our data do suggest that calbindin may offer striatal neurons some protection against moderate excitotoxic insults, and this may explain the reportedly slightly greater vulnerability of striatal neurons that are poor in calbindin to ischemia and Huntington's disease [5].

Psychiatry related information on Calb1

  • In rats stimulated by novel environmental cues during the period of wakefulness preceding perfusion, Fos-positive neurons increased markedly relative to unstimulated animals, and involved the majority of the calbindin- or parvalbumin-labeled cell populations (60-75% and over 95%, respectively) [6].
  • Thirty days after the last of 36 electroconvulsive shocks, the calbindin immunoreactivity was back to normal [7].
  • Cytotoxicity in response to calcium ionophore or amyloid beta-peptide (which accumulates in the brain in Alzheimer's disease and has been reported to be neurotoxic) was measured by MTT reduction in vector transfected cells and in calbindin transfected clones [8].

High impact information on Calb1


Chemical compound and disease context of Calb1


Biological context of Calb1


Anatomical context of Calb1

  • In contrast, only a subset of CALB- and CALR-immunoreactive interneurons (24% and 23%, respectively) displayed hybridization signals for NGF [22].
  • In the present study, calretinin (CALRET) and CALB patterns were determined by Western analysis in the medial basal hypothalamus (MBH) from male rats along with assaying plasma testosterone levels during postnatal development [23].
  • A small percentage of the CA-positive cells in lamina I and in the magnocellular layers were retrogradely labeled from the thalamus [24].
  • Parvalbumin, calbindin, or calretinin in cortically projecting and GABAergic, cholinergic, or glutamatergic basal forebrain neurons of the rat [25].
  • Postembedding immunostaining demonstrated that CB-containing cells contain GABA, whereas CR-positive axon terminals forming asymmetric synapses are devoid of this labeling [26].

Associations of Calb1 with chemical compounds

  • These findings suggest that there is not a clear correspondence between the androgen status in male rats and the calcium-binding proteins (CALRET & CALB) expressed in the MBH [23].
  • Calbindin-positive neurons constituted almost 60% of the GABA-containing population in both subdivisions of the basolateral nucleus and more than 40% of the GABA-containing population in the lateral nucleus [27].
  • Significant proportions of Calb(+) (>40%) and Calret(+) (>80%) neurons were immunopositive for phosphate-activated glutaminase, the synthetic enzyme for transmitter glutamate [25].
  • Most CALB/NGF+ cells were located in the stratum oriens/alveus of the CA3-CA1 regions, suggesting that they may include the population of CALB+, hippocamposeptal, nonpyramidal neurons [28].
  • Combined dual-immunofluorescence and confocal microscopy revealed that somatodendritic alpha4 nicotinic acetylcholine receptors colocalized with cortical neurons stained positively for CR, PV or CB [29].

Physical interactions of Calb1

  • These data indicate that PA and CA antisera identify two cell populations in whisker-related regions of the V brainstem complex and that PA cells are somatotopically patterned in PrV, SpI, and SpC [24].
  • In the lateral septum, 5-HT1A receptor immunoreactivity was colocalized with the calcium-binding protein calbindin D-28k, a marker for septal GABAergic somatospiny neurons [30].
  • We tested whether the rat pineal gland controls the expression of a neuropeptide (neuropeptide Y) and a calcium-binding protein (calbindin) in sympathetic postganglionic neurones that innervate it [31].

Co-localisations of Calb1

  • From the second week, in addition to labeling vestibular afferents in their specific target areas, parvalbumin was also found colocalized with calbindin in mature Purkinje cell afferents [32].
  • Calbindin is largely co-localized with SRIF, and not with VIP [33].
  • On the other hand, calbindin was also found in spinal afferents to the esophagus where it was co-localized with calcitonin gene-related peptide [34].

Regulatory relationships of Calb1

  • In cortical or diencephalic cultures, CR was rarely coexpressed with GABA or calbindin D-28k [35].
  • In layers II to IV of the barrel cortex most PARV-immunoreactive neurons are likely to derive from a subpopulation of CALB-immunoreactive neurons whose CALB immunoreactivity ceases when they begin to express PARV between the second and third postnatal weeks [36].
  • In conclusion, all calbindin-containing cortical interneurons seem to be under direct influence of other GABAergic interneurons expressing the peptide VIP [37].
  • Glial cell line-derived neurotrophic factor stimulates the morphological differentiation of cultured ventral mesencephalic calbindin- and calretinin-expressing neurons [38].
  • A small population of calbindin-positive interneurons and very few calretinin-positive cells express Reln immunopositivity [39].

Other interactions of Calb1

  • All of these are PV, CB, SOM and NOS negative [40].
  • Combined dual immunofluorescence and confocal microscopy further revealed that CRF-ir puncta made possible pericellular contacts on PV-ir (not CB-, CR- or glutamate-ir) cell bodies [41].
  • NC/CB, NC/CR and NC/VIP double-labeled cells were found in all hippocampal regions, and represented 29%, 24% and 18% of the NC-IR cells, respectively [42].
  • With the exception of calbindin-positive interneurons, GluR2/3 was absent from hippocampal interneurons in both rat and monkey [43].
  • 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(+) [25].

Analytical, diagnostic and therapeutic context of Calb1


  1. Expression in Escherichia coli of full-length and mutant rat brain calbindin D28. Comparison with the purified native protein. Gross, M.D., Kumar, R., Hunziker, W. J. Biol. Chem. (1988) [Pubmed]
  2. Calcium buffering properties of calbindin D28k and parvalbumin in rat sensory neurones. Chard, P.S., Bleakman, D., Christakos, S., Fullmer, C.S., Miller, R.J. J. Physiol. (Lond.) (1993) [Pubmed]
  3. Overexpression of calbindin D(28k) in dentate gyrus granule cells alters mossy fiber presynaptic function and impairs hippocampal-dependent memory. Dumas, T.C., Powers, E.C., Tarapore, P.E., Sapolsky, R.M. Hippocampus. (2004) [Pubmed]
  4. Changes in calcium-binding protein expression in the auditory brainstem nuclei of the jaundiced Gunn rat. Spencer, R.F., Shaia, W.T., Gleason, A.T., Sismanis, A., Shapiro, S.M. Hear. Res. (2002) [Pubmed]
  5. Relative resistance of striatal neurons containing calbindin or parvalbumin to quinolinic acid-mediated excitotoxicity compared to other striatal neuron types. Figueredo-Cardenas, G., Harris, C.L., Anderson, K.D., Reiner, A. Exp. Neurol. (1998) [Pubmed]
  6. Fos induction in cortical interneurons during spontaneous wakefulness of rats in a familiar or enriched environment. Bertini, G., Peng, Z.C., Fabene, P.F., Grassi-Zucconi, G., Bentivoglio, M. Brain Res. Bull. (2002) [Pubmed]
  7. Transient decrease in calbindin immunoreactivity of the rat fascia dentata granule cells after repeated electroconvulsive shocks. Tønder, N., Kragh, J., Bolwig, T., Zimmer, J. Hippocampus. (1994) [Pubmed]
  8. Expression of calbindin-D28k in C6 glial cells stabilizes intracellular calcium levels and protects against apoptosis induced by calcium ionophore and amyloid beta-peptide. Wernyj, R.P., Mattson, M.P., Christakos, S. Brain Res. Mol. Brain Res. (1999) [Pubmed]
  9. Protection of dentate hilar cells from prolonged stimulation by intracellular calcium chelation. Scharfman, H.E., Schwartzkroin, P.A. Science (1989) [Pubmed]
  10. Hyperresponsiveness of vitamin D receptor gene expression to 1,25-dihydroxyvitamin D3. A new characteristic of genetic hypercalciuric stone-forming rats. Yao, J., Kathpalia, P., Bushinsky, D.A., Favus, M.J. J. Clin. Invest. (1998) [Pubmed]
  11. Functions of basic fibroblast growth factor and neurotrophins in the differentiation of hippocampal neurons. Vicario-Abejón, C., Johe, K.K., Hazel, T.G., Collazo, D., McKay, R.D. Neuron (1995) [Pubmed]
  12. Cellular targets and trophic functions of neurotrophin-3 in the developing rat hippocampus. Collazo, D., Takahashi, H., McKay, R.D. Neuron (1992) [Pubmed]
  13. Stable transfection of calbindin-D28k into the GH3 cell line alters calcium currents and intracellular calcium homeostasis. Lledo, P.M., Somasundaram, B., Morton, A.J., Emson, P.C., Mason, W.T. Neuron (1992) [Pubmed]
  14. Development of GABA and calcium binding proteins immunoreactivity in the rat hippocampus following neonatal anoxia. Dell'Anna, E., Geloso, M.C., Magarelli, M., Molinari, M. Neurosci. Lett. (1996) [Pubmed]
  15. Differential changes of calcium binding proteins in the rat striatum after kainic acid-induced seizure. Lee, J., Park, K., Lee, S., Whang, K., Kang, M., Park, C., Huh, Y. Neurosci. Lett. (2002) [Pubmed]
  16. Granule-like neurons at the hilar/CA3 border after status epilepticus and their synchrony with area CA3 pyramidal cells: functional implications of seizure-induced neurogenesis. Scharfman, H.E., Goodman, J.H., Sollas, A.L. J. Neurosci. (2000) [Pubmed]
  17. Calbindin D28K gene transfer via herpes simplex virus amplicon vector decreases hippocampal damage in vivo following neurotoxic insults. Phillips, R.G., Meier, T.J., Giuli, L.C., McLaughlin, J.R., Ho, D.Y., Sapolsky, R.M. J. Neurochem. (1999) [Pubmed]
  18. Brain injury and tumor necrosis factors induce calbindin D-28k in astrocytes: evidence for a cytoprotective response. Mattson, M.P., Cheng, B., Baldwin, S.A., Smith-Swintosky, V.L., Keller, J., Geddes, J.W., Scheff, S.W., Christakos, S. J. Neurosci. Res. (1995) [Pubmed]
  19. Nucleotide sequence of cDNA to mRNA for a cerebellar Ca-binding protein, spot 35 protein. Yamakuni, T., Kuwano, R., Odani, S., Miki, N., Yamaguchi, Y., Takahashi, Y. Nucleic Acids Res. (1986) [Pubmed]
  20. Rat brain calbindin D28: six domain structure and extensive amino acid homology with chicken calbindin D28. Hunziker, W., Schrickel, S. Mol. Endocrinol. (1988) [Pubmed]
  21. Cortical neurons containing calretinin are selectively resistant to calcium overload and excitotoxicity in vitro. Lukas, W., Jones, K.A. Neuroscience (1994) [Pubmed]
  22. Expression of NGF and NT3 mRNAs in hippocampal interneurons innervated by the GABAergic septohippocampal pathway. Rocamora, N., Pascual, M., Acsàdy, L., de Lecea, L., Freund, T.F., Soriano, E. J. Neurosci. (1996) [Pubmed]
  23. Calretinin and calbindin-D28K in male rats during postnatal development. Lephart, E.D., Taylor, H., Jacobson, N.A., Watson, M.A. Neurobiol. Aging (1998) [Pubmed]
  24. Parvalbumin and calbindin immunocytochemistry reveal functionally distinct cell groups and vibrissa-related patterns in the trigeminal brainstem complex of the adult rat. Bennett-Clarke, C.A., Chiaia, N.L., Jacquin, M.F., Rhoades, R.W. J. Comp. Neurol. (1992) [Pubmed]
  25. Parvalbumin, calbindin, or calretinin in cortically projecting and GABAergic, cholinergic, or glutamatergic basal forebrain neurons of the rat. Gritti, I., Manns, I.D., Mainville, L., Jones, B.E. J. Comp. Neurol. (2003) [Pubmed]
  26. GABAergic neurons in the rat dentate gyrus are innervated by subcortical calretinin-containing afferents. Nitsch, R., Leranth, C. J. Comp. Neurol. (1996) [Pubmed]
  27. Colocalization of calcium-binding proteins and GABA in neurons of the rat basolateral amygdala. McDonald, A.J., Mascagni, F. Neuroscience (2001) [Pubmed]
  28. Expression of nerve growth factor and neurotrophin-3 mRNAs in hippocampal interneurons: morphological characterization, levels of expression, and colocalization of nerve growth factor and neurotrophin-3. Pascual, M., Rocamora, N., Acsády, L., Freund, T.F., Soriano, E. J. Comp. Neurol. (1998) [Pubmed]
  29. Chronic nicotine exposure during adolescence differentially influences calcium-binding proteins in rat anterior cingulate cortex. Liu, J.J., Mohila, C.A., Gong, Y., Govindarajan, N., Onn, S.P. Eur. J. Neurosci. (2005) [Pubmed]
  30. 5-HT1A receptor mRNA and immunoreactivity in the rat medial septum/diagonal band of Broca-relationships to GABAergic and cholinergic neurons. Lüttgen, M., Ogren, S.O., Meister, B. J. Chem. Neuroanat. (2005) [Pubmed]
  31. Control of postganglionic neurone phenotype by the rat pineal gland. Anderson, C.R., Penkethman, S.L., Bergner, A.J., McAllen, R.M., Murphy, S.M. Neuroscience (2002) [Pubmed]
  32. Calcium-binding proteins map the postnatal development of rat vestibular nuclei and their vestibular and cerebellar projections. Puyal, J., Devau, G., Venteo, S., Sans, N., Raymond, J. J. Comp. Neurol. (2002) [Pubmed]
  33. Immunohistochemical markers in rat cortex: co-localization of calretinin and calbindin-D28k with neuropeptides and GABA. Rogers, J.H. Brain Res. (1992) [Pubmed]
  34. Vagal and spinal afferent innervation of the rat esophagus: a combined retrograde tracing and immunocytochemical study with special emphasis on calcium-binding proteins. Dütsch, M., Eichhorn, U., Wörl, J., Wank, M., Berthoud, H.R., Neuhuber, W.L. J. Comp. Neurol. (1998) [Pubmed]
  35. Vulnerability to calcium-induced neurotoxicity in cultured neurons expressing calretinin. Isaacs, K.R., Wolpoe, M.E., Jacobowitz, D.M. Exp. Neurol. (2000) [Pubmed]
  36. Thalamic and basal forebrain afferents modulate the development of parvalbumin and calbindin D28k immunoreactivity in the barrel cortex of the rat. Alcantara, S., Soriano, E., Ferrer, I. Eur. J. Neurosci. (1996) [Pubmed]
  37. Calbindin-containing interneurons are a target for VIP-immunoreactive synapses in rat primary somatosensory cortex. Staiger, J.F., Masanneck, C., Schleicher, A., Zuschratter, W. J. Comp. Neurol. (2004) [Pubmed]
  38. Glial cell line-derived neurotrophic factor stimulates the morphological differentiation of cultured ventral mesencephalic calbindin- and calretinin-expressing neurons. Widmer, H.R., Schaller, B., Meyer, M., Seiler, R.W. Exp. Neurol. (2000) [Pubmed]
  39. Cortical bitufted, horizontal, and Martinotti cells preferentially express and secrete reelin into perineuronal nets, nonsynaptically modulating gene expression. Pesold, C., Liu, W.S., Guidotti, A., Costa, E., Caruncho, H.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  40. Three distinct families of GABAergic neurons in rat visual cortex. Gonchar, Y., Burkhalter, A. Cereb. Cortex (1997) [Pubmed]
  41. Increases in the density of parvalbumin-immunoreactive neurons in anterior cingulate cortex of amphetamine-withdrawn rats: evidence for corticotropin-releasing factor in sustained elevation. Mohila, C.A., Onn, S.P. Cereb. Cortex (2005) [Pubmed]
  42. Neurocalcin-immunoreactive cells in the rat hippocampus are GABAergic interneurons. Martínez-Guijarro, F.J., Briñón, J.G., Blasco-Ibáñez, J.M., Okazaki, K., Hidaka, H., Alonso, J.R. Hippocampus. (1998) [Pubmed]
  43. AMPA receptors in the rat and primate hippocampus: a possible absence of GluR2/3 subunits in most interneurons. Leranth, C., Szeidemann, Z., Hsu, M., Buzsáki, G. Neuroscience (1996) [Pubmed]
  44. Molecular cloning of cDNA to mRNA for a cerebellar spot 35 protein. Yamakuni, T., Kuwano, R., Odani, S., Miki, N., Yamaguchi, K., Takahashi, Y. J. Neurochem. (1987) [Pubmed]
  45. Partial coexistence of neuropeptide Y and calbindin D28k in the trigeminal ganglion following peripheral axotomy of the inferior alveolar nerve in the rat. Wakisaka, S., Takikita, S., Youn, S.H., Kurisu, K. Brain Res. (1996) [Pubmed]
  46. Changes in structure and stability of calbindin-D(28K) upon calcium binding. Venyaminov, S.Y., Klimtchuk, E.S., Bajzer, Z., Craig, T.A. Anal. Biochem. (2004) [Pubmed]
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