Carnosine improves aging-induced cognitive impairment and brain regional neurodegeneration in relation to the neuropathological alterations in the secondary structure of amyloid beta (Aβ).

Abstract

Aging-induced proteinopathies, including deterioration of amyloid beta (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 this study was to investigate the effects of exogenous carnosine treatments on aging-induced changes (a) in the steady-state level of endogenous carnosine and conformation of Aβ secondary structure in the different brain regions (cerebral cortex, hippocampus, hypothalamus, pons-medulla, and cerebellum) and (b) cognitive function. Young (4months) and aged (18 and 24months) male albino Wistar rats were treated with carnosine (2.0μgkg-1 day-1 ; i.t.) or equivalent volumes of vehicle (saline) for 21 consecutive days and were tested for cognition using 8-arm radial maze test. Brains were processed to assess the conformational integrity of Aβ plaques using Raman spectroscopy and endogenous levels of carnosine were measured in the brain regions using HPLC. Results indicated that carnosine treatments improved the aging-induced deficits in cognitive function and reduced the 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) conformational changes in Aβ secondary structure by reducing the abundance of β-sheets and reductions in carnosine content in the brain regions and (b) cognitive impairment.