Enriched environment alleviates post-stroke cognitive impairment through enhancing α7-nAChR expression in rats

ABSTRACT

Background: Enriched environment (EE) is a simple and effective intervention to improve cognitive function in post-stroke cognitive impairment (PSCI), partly due to the rebalancing of the cholinergic signaling pathway in the hippocampus. α7-nicotinic acetylcholine receptor (α7-nAChR) is a cholinergic receptor whose activation inhibits inflammation and promotes the recovery of neurological function in PSCI patients. However, it is still unclear whether EE can regulate α7-nAChR and activate the cholinergic anti-inflammatory pathway (CAP) in PSCI. Objective: To investigate the effects of EE on cognitive impairment, and the role of α7-nAChR in PSCI. Methods: A PSCI rat model was induced by middle cerebral artery occlusion and reperfusion (MCAO/R) and were reared in standard environment (SE) or EE for 28d, control group with sham surgery. Cognitive function was determined by Morris water maze test. The long-term potentiation (LTP) was assessed by Electrophysiology. Histopathological methods were used to determine infarct volume, α7-nAChR expression and the cytokines and cholinergic proteins expression. Results: Compared with SE group, rats in EE group had better cognitive function, higher expression of α7-nAChR positive neurons in hippocampal CA1 region. In addition, EE attenuated unfavorable changes induced by MCAO/R in cytokines and cholinergic proteins, and also enhanced LTP promoted by nicotine and attenuated by α-BGT; but showed no significantly difference in infarct volume. Conclusions: EE markedly improves cognitive impairment and enhances neuroplasticity in PSCI rats, which may be closely related to enhancement of α7-nAChR expression.

RESUMO

Introdução: O ambiente enriquecido (AE) é uma intervenção simples e eficaz para melhorar a função cognitiva no comprometimento cognitivo pós-AVC, em parte devido ao reequilíbrio da via de sinalização colinérgica no hipocampo. O receptor nicotínico α7 de acetilcolina (α7-nAChR) é um receptor colinérgico cuja ativação inibe inflamação e promove a recuperação da função neurológica em pacientes com comprometimento cognitivo pós-AVC. No entanto, ainda não está claro se o AE pode regular α7-nAChR e ativar a via anti-inflamatória colinérgica (VAC) em comprometimento cognitivo pós-AVC. Objetivo: Investigar os efeitos do AE no comprometimento cognitivo e o papel do α7-nAChR no comprometimento cognitivo pós-AVC. Métodos: Modelo de comprometimento cognitivo pós-AVC foi induzido em ratos por oclusão e reperfusão da artéria cerebral média (MCAO/R), que foram criados em ambiente padrão (AP) ou em AE por 28d; grupo controle com cirurgia simulada. A função cognitiva foi determinada pelo teste do labirinto aquático de Morris. A potenciação de longo prazo (PLP) foi avaliada por eletrofisiologia. Métodos histopatológicos foram usados para determinar o volume do infarto, a expressão de α7-nAChR e a expressão de citocinas e proteínas colinérgicas. Resultados: Em comparação com o grupo AP, os ratos do grupo AE tiveram melhor função cognitiva, com maior expressão de neurônios positivos para α7-nAChR na região CA1 do hipocampo. Além disso, o AE atenuou alterações desfavoráveis induzidas por MCAO/R em citocinas e proteínas colinérgicas, e também aumentou a PLP promovida pela nicotina e atenuada por α-BGT, mas não mostrou nenhuma diferença significativa no volume do infarto. Conclusão: O AE melhora acentuadamente o comprometimento cognitivo e aumenta a neuroplasticidade em ratos com comprometimento cognitivo pós-AVC, o que pode estar intimamente relacionado ao aumento da expressão de α7-nAChR.

Keywords:

Cognitive Dysfunction - Stroke - Hippocampus

Palavras-chave:

Disfunção Cognitiva - Acidente Vascular Cerebral - Hipocampo

Authors’ contributions:

MY: study design, experimental implementation and manuscript drafting. XB: supervision of all experiments and data interpretation. XXZ: experimental implementation and data collection. XCF: data analysis and manuscript revision. All authors have read and approved the manuscript.

Support: This study was supported by the Leading Personnel Training Project of Shanghai Pudong New District Municipal Health Bureau in China, No. PWR12018-04 (to XB); and the Science and Technology Development Fund of Shanghai Pudong New District in China, No. PKJ2018-Y38 (to XB).

Publication History

Received: 11 January 2020

Accepted: 03 March 2020

Article published online:
13 June 2023

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