Cholinergic dysfunctions are correlated with memory deficits in rats exposed to chronic hypoxia-hypercapnia / 中华神经科杂志

ABSTRACT

Objective To investigate the relationship between changes of cholinergic system and memory ability impairment in rats long-term exposed to hypoxia-hypercapnia.Methods Forty-eight SD rats were randomly divided into control group,2 weeks hypoxia-hypercapnia group and 4 weeks hypoxiahypercapnia group.The chronic hypoxia-hypercapnia rat model was set up.The memory ability was assessed by eight-arm radial maze.Morphological changes were observed by the HE staining and Nissl staining.Acetylcholine(ACh) content,choline acetyl-transferase (ChAT) activity and acetyl-cholinesterase (AChE) activity in the hippocampus were detected by spectrophotometry,while expression of α7 neuronal nicotinic acetylcholine receptor (α7 nAChR) protein by Western blot.Results Memory ability,especially the working memory was impaired in rats exposed to chronic hypoxia-hypercapnia.And the memory ability decreased more markedly in four weeks group.Compared with those of normoxic rats,the levels of ACh and the activities of AChE and ChAT in the hippocampus of the two weeks group were significantly decreased (ACh(58.9 ±2.7) vs (47.4 ±3.2) μg/mg (protein) ; AChE(0.326 ±0.019) vs (0.247 ±0.020) U/mg (protein) ; ChAT(127.1 ±8.6) vs (90.4 ±6.9) U/g (tissue wet weight),t =7.674,8.139,9.408,all P ＜ 0.05).Compared with the two weeks group,those changes were more obvious in the four weeks group rats (ACh(47.4 ±3.2) vs (32.5 ±3.2) μg/mg (protein); AChE(0.247 ±0.020),(0.170±0.019) U/mg (protein); ChAT(90.4 ±6.9),(55.6 ±6.0) U/g (tissue wet weight),t =9.279,8.036,10.781,all P ＜ 0.05).Compared with the normoxic rats,the expressions of α7 nAChR protein were significantly decreased in two weeks group rats (t =4.481,P ＜ 0.05).Moreover,the expressions of α7 nAChR protein were significantly decreased in four weeks group rats comparing with the two weeks group (t =4.965,P ＜ 0.05).Conclusions An impairment of rat' s memory ability may be induced by hypoxia-hypercapnia,and the injury degree is correlated with the exposure time.Cholinergic system dysfunctions may contribute to the memory function defects in chronic hypoxia-hypercapnia rats.