期刊
JOURNAL OF NEUROCHEMISTRY
卷 158, 期 3, 页码 710-723出版社
WILEY
DOI: 10.1111/jnc.15357
关键词
Aging; amyloid-beta; carnosine; cognitive function; neurodegeneration
资金
- Science and Engineering Research Board (SERB)
- Indian Council of Medical Research (ICMR), New Delhi, India
The study found that carnosine treatments improved cognitive function deficits induced by aging, reduced beta-sheets in the secondary structure of A beta protein, and mitigated the decrease in carnosine levels and spine density in the examined brain regions. These results suggest that carnosine can attenuate aging-induced conformational changes in A beta secondary structure and cognitive impairment.
Aging-induced proteinopathies, including deterioration of amyloid beta (A beta) conformation, are associated with reductions in endogenous levels of carnosine and cognitive impairments. Carnosine is a well-known endogenous antioxidant, which counteracts aging-induced A beta 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 A beta secondary structure in the different brain regions (cerebral cortex, hippocampus, hypothalamus, pons-medulla, and cerebellum) and (b) cognitive function. Young (4 months) and aged (18 and 24 months) male albino Wistar rats were treated with carnosine (2.0 mu g kg(-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 A beta 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 beta-sheets in the secondary structure of A beta 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 A beta secondary structure by reducing the abundance of beta-sheets and reductions in carnosine content in the brain regions and (b) cognitive impairment.
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