Aging is accompanied by a high level of oxidized form of guanine, 8-oxo-2’deoxyguanosine (8-oxo-2’dG), and decreased level of 8-oxoguanine glycosylase 1 (OGG1) in the brain. The development and progression of neurodegenerative disorders are also characterized by dysfunction or loss of the brain nicotinic acetylcholine receptors (nAChRs). To study whether the differences in nAChRs expression in the rat brain occur due to aging or oxidative stress we analyzed RNA and protein levels of α7, α4 and β2 subunits by RQ-PCR and Western blot validation in three brain structures: cerebral grey matter (CGM), sub-cortical white matter (SCWM) and cerebellum (Ce) of twenty one female Wistar rats. The first group consisted of five 3.0–3.5-month-old females, which was assigned as a young control group. The remaining sixteen females aged of 18–24 month were divided into three following groups: (1) aged control group of 5 rats; (2) a vehicle group of 5 rats which received intraperitoneal injections of deionized water; (3) memantine-treated group of 6 rats. In each group, the selected brain areas have also been analyzed to determinate the levels of oxidative stress. In this study, age- and stress- dependent differential RNA and protein expression levels were approved only in OGG1 and α7 nAChR proteins. In all analyzed brain structures of young and old controls, the levels of oxidized form of guanine were similar. Stress relevant to water injection increased the level of 8-oxo-2’dG in the cerebellum of old control rats (Ce, P<0.05). The old controls demonstrated an important reduction of OGG1 mRNA expression in CGM and Ce regions compared to young individuals (CGM P=0.03; Ce P=0.2). Western blot analysis has also revealed a reduction of OGG1 protein in the sub-cortical white matter of old individuals (SCWM, P=0.03). However, there was no important influence of water administration on OGG1 expression in all brain regions. In all analyzed brain structures, expression of α7 nAChR was down-regulated in old controls compared to young controls. However, this decrease was only significant in SCWM area (SCWM, P<0.05). Treatment with H2O caused a significant increase in RNA and protein levels of α7 nAChR in SCWM as compared to this brain structure of the aged control rats (SCWM, P<0.01). Our results suggest that aging of the rat brain is mostly associated with decreased expression of OGG1 as well as with deficit of α7 nAChR in the sub-cortical white matter. Stress relevant to water injection increases the level of 8-oxo-2’dG in the aging rat brain, but clearly overcomes the α7 nAChR deficit. A significant increase of the α7 nAChR expression in the SCWM of H2O-treated rats suggests that these receptors play an important role in compensatory mechanisms facilitating the impaired cholinergic neurotransmission following oxidative stress in the aging rat brain.
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