A few studies investigated in detail possible relationships between aging cognitive decline and hippocampal astroglial plasticity. In the present report we investigated in murine model possible relationships between performances in object recognition tests and the astrocytes laminar distribution in CA3. To do so, young (6 months old, n = 7) and old (20 months old, n= 5) C57Bl6 mice, were maintained in standard cages and assessed in object recognition hippocampal-dependent tasks. Isolated or integrated (episodic-like memory) tests were applied and revealed that object identity (What?), place (Where?) and time (When?), were impaired in old subjects, whereas in young mice only spatial memory was impaired. After behavioral tests all subjects were sacrificed and perfused with aldehyde fixatives had their
brains removed and processed for glial fibrillary acid protein (GFAP) immunohistochemistry, a selective marker for astrocytes. To avoid sample bias we used the optical fractionator, a stereological method that is no affected by histological procedures. The results on behavioral isolated or integrated tests revealed that aging significantly impairs object, spatial and time recognition (two-tail t-test, p<0.05). As compared to young subjects, old mice showed laminar changes in the astrocytes distribution with proportional increase of the astrocytes number in the pyramidal layer of dorsal and ventral CA3 and a reduction in the lacunosum molecular layer of dorsal CA3. Coherently, the total number of CA3 astrocytes showed significant
reorganization of its laminar distribution as a function of age with reduction of its numbers in the stratum oriens. No significant differences were detected in the mean values of laminar volumes suggesting that aging induced changes directly affected astroglial plasticity in CA3. Finally, a linear inverse correlation was found between the estimations of pyramidal cell layer astrocytes and performances in the behavioral tasks. Further direct evidences of this correlation with altered CA3 astrocytes and possible molecular mechanisms to explain aging cognitive decline remains to be investigated.
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