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Gene Review

Calb2  -  calbindin 2

Rattus norvegicus

Synonyms: CR, Calretinin
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Disease relevance of Calb2

  • The apparent decrease in the number of PV and CR immunoreactive hilar neurons was correlated with the duration of the SE and was most extensive in rats with a progressive form of epilepsy [1].
  • Calretinin and parvalbumin-immunoreactivity was present at a lower level of fluorescence than that of calbindin immunoreactivity in all the neurons of the major pelvic ganglion and this level was unchanged in aged rats [2].
  • CR gene is active in some neurons, such as cerebellar granule neurons and in some tumor cells such as colon adenocarcinoma or epithelial mesothelioma [3].
  • The present data indicate that the striatal calretinin-positive neurons are less resistant to transient ischemia, suggesting that there may exist vulnerability differences among the striatal interneurons in ischemia-induced neuronal injury [4].
  • Calbindin-D28k and calretinin in the rat posterior pituitary; light and electron microscopic localization and upregulation with dehydration [5].

Psychiatry related information on Calb2


High impact information on Calb2


Chemical compound and disease context of Calb2


Biological context of Calb2

  • Virtually every PARV-positive neuron innervated by GABAergic septohippocampal baskets expressed NGF mRNA (86%), whereas 39-59% of CALR- and CALB-positive interneurons that were contacted by GABAergic septohippocampal axons showed NGF gene expression [17].
  • An up-regulation of calretinin and parvalbumin in calyces of Held probably increases the presynaptic Ca(2+) buffering strength during postnatal development, but the unexpected heterogeneity of calretinin expression might cause differences in Ca(2+) signalling and transmitter release probability between calyces of Held [18].
  • Calretinin may still buffer calcium at low concentrations or be a component in a calcium-based signal transduction system [19].
  • Since we found the Mr 29,000 calcium binding protein to be an abundant protein in rat cerebellum, these results suggest either posttranscriptional regulation of calretinin in cerebellum or species differences.(ABSTRACT TRUNCATED AT 250 WORDS)[20]
  • Calbindin, parvalbumin, and calretinin, members of EF-hand calcium-binding proteins, play important roles in buffering intracellular calcium ions [21].

Anatomical context of Calb2

  • Mixed-effects statistical models, adapted specifically for these analyses, indicated that perturbations of amygdalar inputs to the hippocampus significantly alter the drive that hippocampal PVB-, CR-, and CB-IR neurons within the dentate gyrus/CA4 region exercise on CCK-IR terminals within the same region as well as in CA3-1 [22].
  • The numerical density (Nd) of somata showing immunoreactivity (IR) for parvalbumin (PVB) was decreased in dentate gyrus (DG) and the CA4-2 region, while that of calretinin (CR)-IR was decreased in DG and CA2 [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].
  • CR-labelled neurones were bipolar or multipolar with round to ovoid somata (diameters between 8 and 12 microm), and rostrocaudally running dendrites forming a network [24].
  • Postembedding immunostaining demonstrated that CB-containing cells contain GABA, whereas CR-positive axon terminals forming asymmetric synapses are devoid of this labeling [25].

Associations of Calb2 with chemical compounds


Physical interactions of Calb2


Co-localisations of Calb2


Regulatory relationships of Calb2


Other interactions of Calb2

  • 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 [40].
  • In addition, the majority of CR and VIP interneurons exhibited colocalization of both neurochemicals [41].
  • Calretinin- and parvalbumin-immunoreactive neurons in the rat main olfactory bulb do not express NADPH-diaphorase activity [42].
  • They contained CCK, but not CR [43].
  • Only a subpopulation of CR-containing cells, the spiny neurons of the dentate gyrus and CA3 region of the hippocampus were characterized by a strong expression of GluR-A and -D subunit mRNAs [44].

Analytical, diagnostic and therapeutic context of Calb2

  • In order to gather more information about calcium-binding proteins during development, we analyzed the spatiotemporal distribution of PV and CR in the rat auditory brainstem using immunocytochemistry [45].
  • In fact, double in situ hybridization analysis confirmed that most NT-3+ neurons also expressed NGF mRNA, indicating coexpression of both neurotrophins in subpopulations of PARV+ and CALR+ neurons [46].
  • In contrast, when the striatal grafts were examined after 30 days survival using confocal microscopy, only 10% of hNT neurons immunopositive for NuMA were PV+; 19% were CB+/NuMA+, approximately the same percentage as was seen in vitro, and 82% of grafted hNT neurons were CR+ [47].
  • Chronic NIC exposure for 3 weeks in adolescent rats, either via drinking water (the oral group) or by twice daily subcutaneous injections (the injection group), resulted in the expression of high levels of CR proteins in the ACC but not in the parietal cortex [48].
  • Calretinin was also quantified by radioimmunoassay [49].


  1. Progression of temporal lobe epilepsy in the rat is associated with immunocytochemical changes in inhibitory interneurons in specific regions of the hippocampal formation. van Vliet, E.A., Aronica, E., Tolner, E.A., Lopes da Silva, F.H., Gorter, J.A. Exp. Neurol. (2004) [Pubmed]
  2. Decreased calbindin-D28k immunoreactivity in aged rat sympathetic pelvic ganglionic neurons. Corns, R.A., Boolaky, U.V., Santer, R.M. Neurosci. Lett. (2000) [Pubmed]
  3. Calretinin gene promoter activity is differently regulated in neurons and cancer cells. Role of AP2-like cis element and zinc ions. Billing-Marczak, K., Ziemińska, E., Leśniak, W., Łazarewicz, J.W., Kuźnicki, J. Biochim. Biophys. Acta (2004) [Pubmed]
  4. Striatal cells containing the Ca(2+)-binding protein calretinin (protein 10) in ischemia-induced neuronal injury. Yamada, K., Goto, S., Oyama, T., Yoshikawa, M., Nagahiro, S., Ushio, Y. Acta Neuropathol. (1995) [Pubmed]
  5. Calbindin-D28k and calretinin in the rat posterior pituitary; light and electron microscopic localization and upregulation with dehydration. Miyata, S., Nakai, S., Kiyohara, T., Hatton, G.I. J. Neurocytol. (2000) [Pubmed]
  6. Identification of candidate genes involved in somatosensory functions of cranial sensory ganglia. Matsumoto, I., Nagamatsu, N., Arai, S., Emori, Y., Abe, K. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  7. Distribution of calretinin mRNA in the vestibular nuclei of rat and guinea pig and the effects of unilateral labyrinthectomy: a non-radioactive in situ hybridization study. Sans, N., Moniot, B., Raymond, J. Brain Res. Mol. Brain Res. (1995) [Pubmed]
  8. Calretinin-immunoreactive neurons are resistant to beta-amyloid toxicity in vitro. Pike, C.J., Cotman, C.W. Brain Res. (1995) [Pubmed]
  9. New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. Dayer, A.G., Cleaver, K.M., Abouantoun, T., Cameron, H.A. J. Cell Biol. (2005) [Pubmed]
  10. Molecular and physiological diversity of cortical nonpyramidal cells. Cauli, B., Audinat, E., Lambolez, B., Angulo, M.C., Ropert, N., Tsuzuki, K., Hestrin, S., Rossier, J. J. Neurosci. (1997) [Pubmed]
  11. Analysis of rat vestibular hair cell development and regeneration using calretinin as an early marker. Zheng, J.L., Gao, W.Q. J. Neurosci. (1997) [Pubmed]
  12. Cortistatin is expressed in a distinct subset of cortical interneurons. de Lecea, L., del Rio, J.A., Criado, J.R., Alcántara, S., Morales, M., Danielson, P.E., Henriksen, S.J., Soriano, E., Sutcliffe, J.G. J. Neurosci. (1997) [Pubmed]
  13. Involvement of adenosine in retinal ischemia. Studies on the rat. Larsen, A.K., Osborne, N.N. Invest. Ophthalmol. Vis. Sci. (1996) [Pubmed]
  14. GDNF induces the calretinin phenotype in cultures of embryonic striatal neurons. Farkas, L.M., Suter-Crazzolara, C., Unsicker, K. J. Neurosci. Res. (1997) [Pubmed]
  15. Plasticity of neurohypophysial terminals with increased hormonal release during dehydration: ultrastructural and biochemical analyses. Miyata, S., Takamatsu, H., Maekawa, S., Matsumoto, N., Watanabe, K., Kiyohara, T., Hatton, G.I. J. Comp. Neurol. (2001) [Pubmed]
  16. Calretinin-immunoreactive dopaminergic neurons from embryonic rat mesencephalon are resistant to levodopa-induced neurotoxicity. Isaacs, K.R., Wolpoe, M.E., Jacobowitz, D.M. Exp. Neurol. (1997) [Pubmed]
  17. 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]
  18. Developmental expression of the Ca2+-binding proteins calretinin and parvalbumin at the calyx of held of rats and mice. Felmy, F., Schneggenburger, R. Eur. J. Neurosci. (2004) [Pubmed]
  19. Vulnerability to calcium-induced neurotoxicity in cultured neurons expressing calretinin. Isaacs, K.R., Wolpoe, M.E., Jacobowitz, D.M. Exp. Neurol. (2000) [Pubmed]
  20. Brain calbindin-D28k and an Mr 29,000 calcium binding protein in cerebellum are different but related proteins: evidence obtained from sequence analysis by tandem mass spectrometry. Gabrielides, C., McCormack, A.L., Hunt, D.F., Christakos, S. Biochemistry (1991) [Pubmed]
  21. Calcium-binding proteins: differential expression in the rat olfactory cortex after neonatal olfactory bulbectomy. Lim, J.H., Brunjes, P.C. J. Neurobiol. (1999) [Pubmed]
  22. Long-term effects of amygdala GABA receptor blockade on specific subpopulations of hippocampal interneurons. Berretta, S., Lange, N., Bhattacharyya, S., Sebro, R., Garces, J., Benes, F.M. Hippocampus. (2004) [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. Neurones in the adult rat anterior medullary velum. Ibrahim, M., Menoud, P.A., Celio, M.R. J. Comp. Neurol. (2000) [Pubmed]
  25. GABAergic neurons in the rat dentate gyrus are innervated by subcortical calretinin-containing afferents. Nitsch, R., Leranth, C. J. Comp. Neurol. (1996) [Pubmed]
  26. Three distinct families of GABAergic neurons in rat visual cortex. Gonchar, Y., Burkhalter, A. Cereb. Cortex (1997) [Pubmed]
  27. Hippocampal interneurons expressing glutamic acid decarboxylase and calcium-binding proteins decrease with aging in Fischer 344 rats. Shetty, A.K., Turner, D.A. J. Comp. Neurol. (1998) [Pubmed]
  28. Calretinin-containing axons and neurons are resistant to an intrastriatal 6-hydroxydopamine lesion. Tsuboi, K., Kimber, T.A., Shults, C.W. Brain Res. (2000) [Pubmed]
  29. A population of supramammillary area calretinin neurons terminating on medial septal area cholinergic and lateral septal area calbindin-containing cells are aspartate/glutamatergic. Leranth, C., Kiss, J. J. Neurosci. (1996) [Pubmed]
  30. Origin of the cortical layer I in rodents. Jiménez, D., Rivera, R., López-Mascaraque, L., De Carlos, J.A. Dev. Neurosci. (2003) [Pubmed]
  31. Time of origin of unipolar brush cells in the rat cerebellum as observed by prenatal bromodeoxyuridine labeling. Sekerková, G., Ilijic, E., Mugnaini, E. Neuroscience (2004) [Pubmed]
  32. Distribution of calmodulin, calbindin-D28k and calretinin among rat olfactory nerve bundles. Bastianelli, E., Pochet, R. Neurosci. Lett. (1994) [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. Calretinin co-localizes with the NMDA receptor subunit NR1 in cholinergic amacrine cells of the rat retina. Araki, C.M., Hamassaki-Britto, D.E. Brain Res. (2000) [Pubmed]
  35. 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]
  36. Intraganglionic laminar endings in the rat esophagus contain purinergic P2X2 and P2X3 receptor immunoreactivity. Wang, Z.J., Neuhuber, W.L. Anat. Embryol. (2003) [Pubmed]
  37. Brain-derived neurotrophic factor promotes the differentiation of various hippocampal nonpyramidal neurons, including Cajal-Retzius cells, in organotypic slice cultures. Marty, S., Carroll, P., Cellerino, A., Castrén, E., Staiger, V., Thoenen, H., Lindholm, D. J. Neurosci. (1996) [Pubmed]
  38. P2X2 and P2X3 purinoceptors in the rat enteric nervous system. Xiang, Z., Burnstock, G. Histochem. Cell Biol. (2004) [Pubmed]
  39. Basic fibroblast growth factor promotes the generation and differentiation of calretinin neurons in the rat cerebral cortex in vitro. Pappas, I.S., Parnavelas, J.G. Eur. J. Neurosci. (1998) [Pubmed]
  40. 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]
  41. Immunohistochemical characterization of cholecystokinin containing neurons in the rat basolateral amygdala. Mascagni, F., McDonald, A.J. Brain Res. (2003) [Pubmed]
  42. Calretinin- and parvalbumin-immunoreactive neurons in the rat main olfactory bulb do not express NADPH-diaphorase activity. Briñón, J.G., Alonso, J.R., García-Ojeda, E., Crespo, C., Arévalo, R., Aijón, J. J. Chem. Neuroanat. (1997) [Pubmed]
  43. Target selectivity and neurochemical characteristics of VIP-immunoreactive interneurons in the rat dentate gyrus. Hajos, N., Acsady, L., Freund, T.F. Eur. J. Neurosci. (1996) [Pubmed]
  44. AMPA receptor subunits are differentially expressed in parvalbumin- and calretinin-positive neurons of the rat hippocampus. Catania, M.V., Bellomo, M., Giuffrida, R., Giuffrida, R., Stella, A.M., Albanese, V. Eur. J. Neurosci. (1998) [Pubmed]
  45. Distribution of the calcium-binding proteins parvalbumin and calretinin in the auditory brainstem of adult and developing rats. Lohmann, C., Friauf, E. J. Comp. Neurol. (1996) [Pubmed]
  46. 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]
  47. Comparison of calcium-binding proteins expressed in cultured hNT neurons and hNT neurons transplanted into the rat striatum. Saporta, S., Willing, A.E., Zigova, T., Daadi, M.M., Sanberg, P.R. Exp. Neurol. (2001) [Pubmed]
  48. 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]
  49. Distribution of calretinin, calbindin D28k, and parvalbumin in subcellular fractions of rat cerebellum: effects of calcium. Winsky, L., Kuźnicki, J. J. Neurochem. (1995) [Pubmed]
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