Περίληψη:
Cend1 is a neuronal-lineage specific modulator involved in coordination of cell cycle exit and differentiation of neuronal precursors. We have previously shown that Cend1−/− mice show altered cerebellar layering caused by increased proliferation of granule cell precursors, delayed radial granule cell migration and compromised Purkinje cell differentiation, leading to ataxic gait and deficits in motor coordination. To further characterize the effects of Cend1 genetic ablation we determined herein a range of behaviors, including anxiety and exploratory behavior in the elevated plus maze (EPM), associative learning in fear conditioning, and spatial learning and memory in the Morris water maze (MWM). We observed significant deficits in all tests, suggesting structural and/or functional alterations in brain regions such as the cortex, amygdala and the hippocampus. In agreement with these findings, immunohistochemistry revealed reduced numbers of γ amino butyric acid (GABA) GABAergic interneurons, but not of glutamatergic projection neurons, in the adult cerebral cortex. Reduced GABAergic interneurons were also observed in the amygdala, most notably in the basolateral nucleus. The paucity in GABAergic interneurons in adult Cend1−/− mice correlated with increased proliferation and apoptosis as well as reduced migration of neuronal progenitors from the embryonic medial ganglionic eminence (MGE), the origin of these cells. Further we noted reduced GABAergic neurons and aberrant neurogenesis in the adult dentate gyrus (DG) of the hippocampus, which has been previously shown to confer spatial learning and memory deficits. Our data highlight the necessity of Cend1 expression in the formation of a structurally and functionally normal brain phenotype. © 2019 Segklia, Stamatakis, Stylianopoulou, Lavdas and Matsas.
Συγγραφείς:
Segklia, K.
Stamatakis, A.
Stylianopoulou, F.
Lavdas, A.A.
Matsas, R.
Λέξεις-κλειδιά:
4 aminobutyric acid; calbindin; calcium binding protein; caspase 3; cell cycle exit and neuronal differentiation protein 1; doublecortin; glial fibrillary acidic protein; Ki 67 antigen; nerve protein; neuron specific nuclear protein; parvalbumin; somatostatin; tau protein; transcription factor Sox2; unclassified drug, amnesia; amygdala; animal experiment; animal model; animal tissue; anxiety; anxiety disorder; apoptosis; Article; associative learning test; ataxic gait; basolateral amygdala; brain; brain cortex; cell migration; cell proliferation; cognitive defect; confocal microscopy; controlled study; dentate gyrus; elevated plus maze test; embryo; exploratory behavior; fear conditioning test; GABAergic transmission; gene expression; genotype; glutamatergic synapse; hippocampus; immunofluorescence; immunohistochemistry; interneuron; Morris water maze test; motor coordination; mouse; nervous system development; neurotransmission; nonhuman; phenotype; protein expression; spatial learning
