Abstract
Aging-induced proteinopathies, including deterioration of Aβ conformation are associated with reductions in endogenous levels of carnosine and cognitive impairments. Carnosine is a well-known endogenous antioxidant which counteracts aging-induced Aβ plaque formation. The aim of the present study was to investigate the effects of exogenous carnosine treatments on aging-induced changes (a) in the brain regional (cerebral cortex, hippocampus, hypothalamus, pons-medulla and cerebellum) steady state level of endogenous carnosine and conformation of Aβ secondary structure and (b) cognitive function. Male albino Wistar rats of young (4 months) and aged (18 and 24 months) were treated with carnosine (2.0 μg/kg/day; i.t.) or equivalent volumes of vehicle (saline) for 21 consecutive day and were tested for cognition using 8-arm radial maze test and brains were processed to assess the conformational integrity of Aβ plaques using Raman spectroscopy and measured the brain regional endogenous levels of carnosine using HPLC. Results indicated that carnosine treatments reduced aging-induced cognitive deficits and increase in β-sheets in the secondary structure of Aβ protein, as well as mitigating the reduction in the steady-state levels of carnosine and spine density in the brain regions examined. These results thus suggest that carnosine can attenuate the aging-induced: (a) brain regional (i) conformational changes of Aβ secondary structure by reducing the abundance of β-sheets; (ii) reductions in carnosine content; and (b) cognitive impairment.
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