Disease relevance of Calb2

• In scrapie infected mice, cortical PV+ neurons were severely reduced while CB+ and CR+ neurons were well preserved [1].
• At the chronic stage, i.e. at 2 months after pilocarpine-induced status epilepticus, significant reduction of CCR7-10 expression in CB-, CR- and PV-immunpositive interneurons may suggest the phenotype change of surviving interneurons [2].
• Calretinin immunoreactivity then appeared in IHCs, OHCs, and ganglion neurons of the medial turn, then of the apical turn [3].
• Calretinin-deficient (Cr-/-) mice present motor discoordination, suggesting cellular and network cerebellar dysfunctions [4].
• CR supplementation significantly attenuated weight loss in tumor-bearing mice without changing food intake or tumor growth [5].

Psychiatry related information on Calb2

• There was also no overlap between calretinin and GR early postnatally (P8) or after physical activity or exposure to an enriched environment, both of which are potent neurogenic stimuli [6].

High impact information on Calb2

• This reduction preferentially affects calretinin(+) (bipolar cells) and somatostatin(+) subtypes (for example, bitufted cells), whereas parvalbumin(+) subpopulations (basket cells and chandelier cells) seem to be unaffected [7].
• Here we show that the recently identified zinc finger transcription factor Sp8 is expressed in neurogenic regions, which give rise to olfactory bulb interneurons at embryonic and postnatal time points and remains expressed in the calretinin-expressing and GABAergic/nondopaminergic interneurons of the glomerular layer [8].
• In ERbeta(-/-) mice, calretinin expression was markedly lower than in WT mice in the hippocampus, thalamus, and amygdala both at E16.5 and at E18 [9].
• Among these CR cell-specific genes, 25 genes, including the CR cell marker genes such as the reelin and calretinin genes, are selectively and highly expressed in both embryonic and postnatal CR cells [10].
• The firing behavior of Purkinje cells is severely affected in Cr-/- alert mice, with alterations of simple spike firing rate, complex spike duration, and simple spike pause [11].

Biological context of Calb2

• In these models the induction of cell proliferation was paralleled by an increase of CR-positive cells, indicating the stimulus-dependent progression from cell division to a postmitotic stage [12].
• Staining for Ki-67 confirmed that no CR-expressing cells were in cell cycle [12].
• Calbindin, calretinin, or parvalbumin and 5-bromo-2'-deoxyuridine (BrdU) double labeling showed that calcium binding protein immunopositive neurons in gliotic CA1 area at 60 days were surviving instead of newly generated neurons [13].
• Calretinin and calbindin D-28k delay the onset of cell death after excitotoxic stimulation in transfected P19 cells [14].
• Deletion of the Pemt gene increases progenitor cell mitosis, DNA and protein methylation and decreases calretinin expression in embryonic day 17 mouse hippocampus [15].

Anatomical context of Calb2

• In CA1 area and the hilus of the dentate gyrus of the mouse hippocampus, drastic reduction of NeuN, calbindin, calretinin, or parvalbumin immunopositive neurons was shown at 3, 7 and 60 days after pilocarpine-induced status epilepticus [13].
• Age-related changes in calbindin D-28k and calretinin immunoreactivity in the inferior colliculus of CBA/CaJ and C57Bl/6 mice [16].
• By contrast, the amounts of other amacrine cell subpopulations (calretinin-, tyrosine hydroxylase-, and parvalbumin-expressing) were increased, whereas the amounts of Islet1/2-expressing retinal ganglion cells were decreased [17].
• Based on calretinin expression in axons, the core/shell compartments of the dorsal claustrum start to be clearly seen at embryonic day 18.5 and may be related to the development of the thalamoclaustral input [18].
• Calretinin (CR) immunoreactivity could be observed in a few cells and fibers in the pallial amygdala at E14.5, and by E16.5 it became a good marker of the different nuclei of the basolateral amygdalar complex [19].

Associations of Calb2 with chemical compounds

• BrdU/CR-labeled cells were negative for GABA and GABAA1 receptor, but early on expressed granule cell marker Prox-1 [12].
• CR expression was detected as early as 1 day after labeling dividing cells with bromodeoxyuridine (BrdU), but not before [12].
• CR- and CB-expressing cells were protected from death during the first 2 h of exposure to NMDA [14].
• Expression of calcium binding proteins, calretinin and calbindin-D28K, normally widely seen in dorsal horn interneurons, was up-regulated on the DCP-treated side [20].
• Expression of high levels of exogenous calbindin or calretinin decreased transcription mediated by PCE1 in Purkinje cells 2.5- to 3-fold, whereas the presence of 1 microM ionomycin in the extracellular medium increased expression [21].

Co-localisations of Calb2

• Early after BrdU, CR colocalized with immature neuronal marker doublecortin; and later with persisting neuronal marker NeuN [12].

Regulatory relationships of Calb2

• Apparently normal motor cortex of mutant fetuses was found to have dramatically reduced presence of nestin-expressing processes of neural precursors, calretinin-expressing pyramidal neurons and calbindin-expressing neurons [22].
• Interestingly, calretinin-expressing bipolar interneurons were nearly absent from cortical cultures of Dlx1/2 mutants [23].
• Evidence is reviewed that suggests bipolar calretinin expressing interneurons may have distinct origins from those that express parvalbumin or somatostatin [24].

Other interactions of Calb2

• Indeed, chronic exposure of cultured cortical neurons for 5 days to increasing concentrations of BDNF (0.1-10 ng/ml) resulted in a concentration-dependent decrease in the number of calretinin-positive neurons and a concentration-dependent increase in the number of calbindin-immunoreactive neurons [25].
• Thus, our data show an important species difference in the chemical distinction of inhibitory neuron subtypes, and indicate that colocalization of CR in SST cells correlates with different morphological and physiological features [26].
• However, calretinin- and calbindin-immunoreactive cells were not Pax-6 immunopositive [27].
• Interestingly, calretinin immunoreactive neurons, which contribute a minor subpopulation, were not affected suggesting that neurotrophin-3 independent regulation of neurogenesis occurs in addition to prominent neurotrophin-3 dependent mechanisms [28].
• We also found decreased calretinin labeling in Pemt-/- (down to 43% compared to wild-type mice; p<0.01) [15].

Analytical, diagnostic and therapeutic context of Calb2

• CalR immunohistochemistry and bromo-deoxyuridine birthdating confirmed the abnormality in position of the earliest generated cortical cells of mutants [29].
• We have generated Cr-deficient (Cr-/-) mice by gene targeting and have investigated the associated phenotype [30].
• In this second study, we have combined two-photon calcium imaging with whole-cell recording and anatomic reconstructions to directly characterize synaptically evoked calcium signals in three types of mouse V1 supragranular interneurones: parvalbumin-positive fast spikers (FS), calretinin-positive irregular spikers (IS), and adapting cells (AD) [31].
• Double immunofluorescence staining procedures were used for tyrosine hydroxylase (a dopaminergic cell marker) and Calbindin-D28k or calretinin [32].
• Double immunofluorescence and confocal microscopy showed that mossy terminals of CR-positive (CR(+)) UBCs were immunoreactive for VGLUT1 and VGLUT2, while mossy terminals of mGluR1alpha-positive (mGluR1alpha(+)) UBCs were provided with VGLUT1 only [33].

References