N-Pep-Zn Improves Cognitive Functions and Acute Stress Response Affected by Chronic Social Isolation in Aged Spontaneously Hypertensive Rats (SHRs)

N-Pep-Zn 可改善老年自发性高血压大鼠 (SHR) 的认知功能和因慢性社会隔离而产生的急性应激反应

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作者:Mikhail Y Stepanichev, Mikhail V Onufriev, Yulia V Moiseeva, Olga A Nedogreeva, Margarita R Novikova, Pavel A Kostryukov, Natalia A Lazareva, Anna O Manolova, Diana I Mamedova, Victoria O Ovchinnikova, Birgit Kastberger, Stefan Winter, Natalia V Gulyaeva

Conclusions

N-pep-Zn enhanced the adaptive capabilities towards chronic (isolation) and acute (immobilization) stress in aged SHRs and prevented cognitive disturbances induced by chronic isolation, probably affecting the hypothalamo-pituitary-adrenal, sympathetic, and immune systems.

Methods

Nine-month-old SHRs were subjected to social isolation for 3 months (SHRiso group), and one group received N-pep-Zn orally (SHRisoP, 1.5 mg/100 g BW). SHRs housed in groups served as the control (SHRsoc). The behavioral study included the following tests: sucrose preference, open field, elevated plus maze, three-chamber sociability and social novelty and spatial learning and memory in a Barnes maze. Levels of corticosterone, glucose and proinflammatory cytokines in blood plasma as well as salivary amylase activity were measured. Restraint (60 min) was used to test acute stress response.

Results

Isolation negatively affected the SHRs learning and memory in the Barnes maze, while the treatment of isolated rats with N-Pep-Zn improved their long-term memory and working memory impairments, making the SHRisoP comparable to the SHRsoc group. Acute stress induced a decrease in the relative thymus weight in the SHRiso group (but not SHRsoc), whereas treatment with N-Pep-Zn prevented thymus involution. N-pep-Zn mitigated the increment in blood cortisol and glucose levels induced by acute stress. Conclusions: N-pep-Zn enhanced the adaptive capabilities towards chronic (isolation) and acute (immobilization) stress in aged SHRs and prevented cognitive disturbances induced by chronic isolation, probably affecting the hypothalamo-pituitary-adrenal, sympathetic, and immune systems.

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