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Parvalbumin and Neuropeptide Y Neuronal Loss in the Hippocampal CA1 Subarea is Associated with Cognitive Deficits in a Rat Model of Chronic Cerebral Hypoperfusion

Author(s): Yue Hei, Lizhou Wei, Xicai Yi, Weiping Liu, Qianfa Long


Background:  Permanent bilateral common carotid artery occlusion (BCCAO) produces a chronic cerebral hypoperfusion (CCH) state, which may cause cognitive impairments in aging, Alzheimer’s disease and vascular dementia. Recent studies have noticed the crucial role of gamma amino butyric acid (GABA)ergic system in regulation of cognitive ability in a rat model of CCH, but the pathological processes of hippocampal GABAergic interneurons in CCH has not been systematically investigated so far. Here we investigated the altered amounts of GABAergic interneurons, namely parvalbumin (PV)-, neuropeptide Y (NPY)- and somatostatin (SOM)- positive cells and their possible relationship with cognitive deficits.

Methods:  55 male Sprague Dawley (SD) rats were randomly divided into BCCAO group (n=33, treated with permanent BCCAO) and sham group (n=22, same operation without ligation). Four weeks later, Morris Water Maze was used to analyze the cognitive deficits, and immunohistochemistry or western blotting was employed to investigate the GABAergic expression in the hippocampus of the rat model.

Results: BCCAO model presented obvious cognitive deficits and neuronal loss, specifically, the expression of PV and NPY in CA1 subarea significantly decreased in comparison to the sham group (PV, *P=0.0233<0.05 for immunofluorescence and *P=0.0272<0.05 for western blotting; NPY, **P=0.0024<0.01 for immunofluorescence and *P=0.0391<0.05 for western blotting). In addition, Pearson’s correlation analysis revealed that spatial learning and memory ability was correlated with the number of PV- and NPY-positive cells (spatial learning: r=-0.6824, **P=0.0072<0.01 for PV and r=-0.7292, **P=0.0031<0.01 for NPY; spatial memory: r=0.7039, **P=0.0050<0.01 for PV and r=0.6887, **P=0.0065<0.01 for NPY).

Conclusions: PV- and NPY-positive cell loss in the hippocampal CA1 subarea is involved in the cognitive impairment in a rat model of CCH.

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