跑台运动对血管痴呆大鼠学习记忆的影响及其作用机制

doi:10.16098/j.issn.0529-1356.2023.03.004

解剖学报 ›› 2023, Vol. 54 ›› Issue (3): 276-282.doi: 10.16098/j.issn.0529-1356.2023.03.004

跑台运动对血管痴呆大鼠学习记忆的影响及其作用机制

贺继平¹ 苏晓云^2*崔建梅³ 张晓宇⁴ 门杰⁵周琛婓³

1. 山西医科大学汾阳学院解剖学教研室，山西汾阳032200; 2. 山西医科大学汾阳学院护理学系，山西汾阳032200; 3. 中北大学体育学院运动医学研究所，太原030051; 4. 山西省汾阳医院精神科，山西汾阳032200; 5. 山医医科大学汾阳学院体育教研室，山西汾阳032200

收稿日期:2022-11-08 修回日期:2023-01-04 出版日期:2023-06-06 发布日期:2023-06-06
通讯作者: 苏晓云 E-mail:694137579@qq.com
基金资助:
山西省自然科学基金;2021年度山西省研究生教育创新项目;2022年度山西医科大学汾阳学院科研基金项目

Effects of treadmill exercise on learning and memory of the vascular dementia rats and its mechanism

HE Ji-ping¹ SU Xiao-yun^2* CUI Jian-mei³ ZHANG Xiao-yu⁴MEN Jie⁵ ZHOU Chen-fei³

1.Department of Anatomy, Fenyang College of Shanxi Medical University, Shanxi Fenyang032200, China; 2. Department of Nursing, Fenyang College of Shanxi Medical University, Shanxi Fenyang032200, China; 3.Institute of Sport and Exercise Medicine，College of PE，North University of China, Taiyuan030051,China; 4.Psychiatry Department, Shanxi Province Fenyang Hospital, Shanxi Fenyang032200, China; 5. Department of Sports，Fenyang College of Shanxi Medical University, Shanxi Fenyang032200, China

Received:2022-11-08 Revised:2023-01-04 Online:2023-06-06 Published:2023-06-06
Contact: SU Xiao-yun E-mail:694137579@qq.com

摘要/Abstract

摘要：

目的观察4周低强度跑台运动对血管痴呆（VD）大鼠空间学习记忆能力，前额叶皮质（PFC）氨基酸水平及蛋白激酶A（PKA）/环磷酸腺苷反应元件结合蛋白（CREB）/脑源性神经营养因子（BDNF）信号通路蛋白表达的影响。方法 39只SD大鼠随机分为假手术组（sham，n=13）、血管痴呆组（VD，n=13）及血管痴呆运动组（VD+EX，n=13）。VD组及VD+EX组大鼠采用双侧颈总动脉永久性结扎法制备慢性脑缺血大鼠模型，然后VD+EX组大鼠进行4周低强度跑台运动。运动结束后，利用水迷宫实验（MWM）评估大鼠学习记忆能力，高效液相色谱法（HPLC）检测大鼠PFC区神经递质谷氨酸（Glu）及 γ-氨基丁酸（GABA）水平，利用Western blotting检测大鼠PFC组织PKA、CREB及BDNF蛋白表达。结果 MWM实验结果显示，VD组大鼠第1~5天平均逃避潜伏期较假手术组显著增加，初次找到原平台时间延长，穿越平台次数显著下降（P<0.01）。经过4周低强度跑台运动，VD+EX组大鼠第1~5天平均逃避潜伏期较VD组显著下降，初次找到原平台时间缩短，穿越平台次数显著增加（P<0.01，P<0.05）。HPLC及Western blotting检测显示，与sham组比较，VD组大鼠PFC区Glu、GABA水平及PFC组织PKA、CREB及BDNF蛋白表达均显著下降（P<0.01）；与VD组大鼠比较，VD+EX组大鼠PFC区Glu 水平及PFC组织PKA、CREB及BDNF蛋白表达均显著增加（P<0.01，P<0.05），GABA水平两组之间差异无显著性（P>0.05）。结论 4周低强度跑台运动可通过增加VD大鼠Glu的释放，并激活PKA/CREB/BDNF通路提升PFC区BDNF表达，从而改善VD大鼠的学习记忆能力。

关键词: 血管痴呆, 跑台运动, 氨基酸类神经递质, 蛋白激酶A/环磷酸腺苷反应元件结合蛋白/脑源性神经营养因子信号通路, 前额叶皮质, 免疫印迹法, 大鼠

Abstract:

Objective To observe the effects of 4-week low intensity treadmill exercise on the learning and memory, amino acid levels and the protein expression of protein kinase A(PKA), cyclic adenosine monophosphate response element binding protein(CREB) and brain-derived neurotrophic factor(BDNF) in the prefrontal cortex (PFC) of the vascular dementia (VD) rats. Methods Thirty-nine SD rats were randomly allocated to 3 groups, sham group (sham, n=13), vascular dementia group (VD, n=13) and vascular dementia treaded with exercise group (VD+EX, n=13). Chronic cerebral ischemia model in VD group and VD+EX group rats were established by permanent ligation of bilateral, then VD+EX group rats were submitted to 4-week low intensity treadmill exercise. After exercise, spatial learning and memory ability were evaluated by Morris water maze test (MWM), glutamic (Glu) and gamma-aminobutyric acid (GABA) levels in the PFC were measured by high performance liquid chromatography(HPLC); the protein expression of PKA, CREB and BDNF in the PFC of rats were detected by Western blotting. Results The result of the MWM showed the average escape latency of rats in the VD group on the 1-5 days was significantly higer than sham group, the time to first find the original platform was significantly prolonged and the platform crossings decreased significantly(P<0.01). The average escape latency of rats treated with four-week low intensity treadmill exercise on the 1-5 days was significantly lower than VD group, the time to first find the original platform was significantly shortened and the platform crossings increased significantly(P<0.01). HPLC and Western blotting detection showed that the levels of Glu and GABA and the protein expression of PKA, CREB and BDNF in the PFC decreased significantly in VD group rats when compared with sham group (P<0.01). Glu level and the protein expression of PKA, CREB and BDNF in the PFC of rats increased significantly(P<0.05) in VD+EX group rats when compared with VD group rats, but GABA level was not significant difference (P>0.05) between the two groups. Conclusion Four-week low-intensity running exercise improves the learning and memory ability of VD rats through enhancing the Glu level and activating PKA-CREB-BDNF signaling in the PFC of rats.

Key words: Vascular dementia, Treadmill exercise, Amino acid neurotransmitter, Protein kinase A/cyclic adenosin monophosphate response element binding protein/brain derived neurotrophic factor signal pathway, Prefrontal cortex, Western blotting, Rat

中图分类号:

R749.1

贺继平苏晓云崔建梅张晓宇门杰周琛婓. 跑台运动对血管痴呆大鼠学习记忆的影响及其作用机制[J]. 解剖学报, 2023, 54(3): 276-282.

HE Ji-ping SU Xiao-yun CUI Jian-mei ZHANG Xiao-yu MEN Jie ZHOU Chen-fei . Effects of treadmill exercise on learning and memory of the vascular dementia rats and its mechanism[J]. Acta Anatomica Sinica, 2023, 54(3): 276-282.

参考文献

［1］Graff-Radford J. Vascular cognitive impairment［J］. Continuum (Minneap Minn), 2019, 25(1):147-164.

［2］Matthews FE, Arthur A, Barnes LE, et al. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study Ⅰ and Ⅱ［J］. Lancet, 2013,382(9902):1405-1412.

［3］Lin CH, Yang HT, Lane HY. D-glutamate, D-serine, and D-alanine differ in their roles in cognitive decline in patients with Alzheimer’s disease or mild cognitive impairment［J］. Pharmacol Biochem Behav, 2019,185:172760.

［4］Liu J, Wu YY, Yu XL, et al. Temporal effect of acupuncture on amino acid neurotransmitters in rats with acute cerebral ischaemia［J］. Acupunct Med, 2019,37(4):252-258.

［5］Tata DA, Dandi E, Spandou E. Expression of synaptophysin and BDNF in the medial prefrontal cortex following early life stress and neonatal hypoxia-ischemia［J］. Dev Psychobiol, 2021,63(2):173-182.

［6］Dietz RM, Orfila JE, Rodgers KM, et al. Juvenile cerebral ischemia reveals age-dependent BDNF-TrkB signaling changes: novel mechanism of recovery and therapeutic intervention［J］. J Cereb Blood Flow Metab, 2018,38(12):2223-2235.

［7］Du XP, Yan HM, Liang JY, et al. Effects of sodium ferulate on cognitive improvement and expression of p-ERK, p-CREB, and BDNF in chronic cerebral hypoperfusion rats［J］. Medical Journal of Wuhan University(Medical Edition), 2017,38 (5):713-718. (in Chinese)

杜雪蓓, 燕灏敏, 梁津瑜, 等. 阿魏酸钠对慢性脑低灌注大鼠认知功能及对磷酸化ERK、CREB和BDNF表达的影响［J］. 武汉大学学报(医学版), 2017,38(5):713-718.

［8］Han P, Zhang W, Kang L, et al. Clinical evidence of exercise benefits for stroke［J］. Adv Exp Med Biol, 2017,1000:131-151.

［9］Shimada H, Hamakawa M, Ishida A, et al. Low-speed treadmill running exercise improves memory function after transient middle cerebral artery occlusion in rats［J］. Behav Brain Res, 2013,243:21-27.

［10］Venkat P, Chopp M, Chen J. Models and mechanisms of vascular dementia［J］. Exp Neurol, 2015,272:97-108.

［11］Zhang M, Ma WCh, Cao WJ, et al. Improvement of Astaxanthin on learning and memory ability of vascular dementia mice［J］. Acta Anatomica Sinica, 2022,53(1):5-10. (in Chinese)

张明, 马卫成, 曹伟娟, 等. 虾青素提高血管性痴呆小鼠学习记忆能力［J］. 解剖学报, 2022,53(1):5-10.

［12］Cong L, Zhang ZhL. Behavioral dynamic evaluation of vascular dementia rat models by bilateral common carotid artery occlusion ［J］. Laboratory Animal and Comparative Medicine, 2020,40(1):22-27. (in Chinese)

从琳, 张智龙. 双侧颈总动脉闭塞法制作血管性痴呆大鼠模型的行为学动态评估［J］. 实验动物与比较医学, 2020,40(1):22-27.

［13］Wang F, Geng X, Tao HY, et al. The restoration after repetitive transcranial magnetic stimulation treatment on cognitive ability of vascular dementia rats and its impacts on synaptic plasticity in hippocampal CA1 area［J］. J Mol Neurosci, 2010,41(1):145-155.

［14］Trigiani LJ, Royea J, Tong XK, et al. Comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia［J］. FASEB J, 2019,33 (12):13280-13293.

［15］Lan X, Zhang M, Yang W, et al. Effect of treadmill exercise on 5-HT, 5-HT1A receptor and brain derived neurophic factor in rats after permanent middle cerebral artery occlusion［J］. Neurol Sci, 2014,35(5):761-766.

［16］Sundseth A, Thommessen B, Rnning OM. Outcome after mobilization within 24 hours of acute stroke: a randomized controlled trial［J］. Stroke, 2012,43(9):2389-2394.

［17］Chen T, Wang Y, Zhang J, et al. Abnormal concentration of GABA and glutamate in the prefrontal cortex in schizophrenia.-an in vivo 1H-MRS study［J］. Shanghai Arch Psychiatry, 2017,29(5):277-286.

［18］Lin S, Zhou G, Shao W, et al. Impact of dexmedetomidine on amino acid contents and the cerebral ultrastructure of rats with cerebral ischemia-reperfusion injury［J］. Acta Cir Bras, 2017,32(6):459-466.

［19］Phillis JW, O’Regan MH. Characterization of modes of release of amino acids in the ischemic/reperfused rat cerebral cortex［J］. Neurochem Int, 2003,43(45):461-467.

［20］Gao Y, Ya B, Li X, et al. Myricitrin ameliorates cognitive deficits in MCAO cerebral stroke rats via histone acetylation-induced alterations of brain-derived neurotrophic factor［J］. Mol Cell Biochem, 2021,476(2):609-617.

［21］Merlio JP, Ernfors P, Kokaia Z, et al. Increased production of the TrkB protein tyrosine kinase receptor after brain insults［J］. Neuron, 1993,10(2):151-164.

［22］Zhao J, Ren J, Liu S, et al. Repeated exposure to sevoflurane in neonatal rats impairs cognition in adulthood via the PKA-CREB-BDNF signaling pathway［J］. Exp Ther Med, 2021,22(6):1442.

［23］Wu L, Zhao QS, Li TW, et al. Yifei Xuanfei Jiangzhuo formula, a Chinese herbal decoction, improves memory impairment through inhibiting apoptosis and enhancing PKA/CREB signal transduction in rats with cerebral ischemia/reperfusion［J］. Mol Med Rep, 2015,12(3):4273-4283.

［24］Soya H, Nakamura T, Deocaris CC, et al. BDNF induction with mild exercise in the rat hippocampus［J］. Biochem Biophys Res Commun, 2007,358(4):961-967.

［25］Hardingham GE, Fukunaga Y, Bading H. Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways［J］. Nat Neurosci, 2002,5(5):405-414.

［26］Wang LS, Tao X, Liu XM, et al. Cajaninstilbene acid ameliorates cognitive impairment induced by intrahippocampal injection of amyloid-β1-42 oligomers［J］. Front Pharmacol, 2019,10:1084.

［27］Lin R, Li L, Zhang Y, et al. Electroacupuncture ameliorate learning and memory by improving N-acetylaspartate and glutamate metabolism in APP/PS1 mice［J］. Biol Res, 2018,51 (1):21.

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跑台运动对血管痴呆大鼠学习记忆的影响及其作用机制

Effects of treadmill exercise on learning and memory of the vascular dementia rats and its mechanism

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