The effect of bone marrow mesenchymal stem cells transplantation on the cognitive ability in a rat model of vascular dementia

doi:10.3877/cma.j.issn.2095-9141.2015.05.007

Abstract

Abstract:

Objective

To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on bilateral common carotid artery occlusion (2VO)-induced cognitive impairments and expression of GAD67 and GABABR1 in the hippocampal CA1 subfield.

Methods

60 adult male SD rats were randomly divided into Sham group (n=20), group (n=20) and BMSCs group (n=20). BMSCs transplantation was performed 2 h after the surgery of 2VO. After 28 days, Morris Water Maze (MWM) test was performed to investigate the cognitive changes, and Western blot and immunohistochemistry were used to evaluate the expression of GAD67 and GABABR1 in the hippocampal CA1 subfield.

Results

(1)Western blot and immunohistochemistry showed that compared to sham group, the expression of GAD67 and GABABR1 (protein level and the intensity of immunohistochemical staining) lowered(1.347±0.357 vs. 2.237±0.956, t=5.478, P=0.0076; 0.779±0.181 vs. 1.691±0.337, t=4.893, P=0.0073, respectively). (2)while BMSCs transplants partly reversed these changes(1.611±1.007 vs. 1.347±0.357, t=2.379, P=0.0373; 1.009±0.257 vs. 0.779±0.181, t=2.678, P=0.0441, respectively). (3)MWM also showed that cognitive ability in the BMSCs group improved significantly (20.817±2.891 vs. 30.192±3.472, t=2.743, P=0.0442) compared to VaD group.

Conclusion

BMSCs transplantation could improve the expression of GAD67 and GABABR1 in the hippocampal CA1 subfield and restore the cognitive ability in a rat model of vascular dementia.

Key words: Bone marrow mesenchymal stem cells, Vascular dementia, Cell transplantation, GAD67, GABABR1

Yue Hei, Cairui Fan, Qianfa Long, Qiang Luo, Lizhou Wei, Xicai Yi, Weiping Liu. The effect of bone marrow mesenchymal stem cells transplantation on the cognitive ability in a rat model of vascular dementia[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2015, 01(05): 25-29.

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References 20

[1]	Iadecola C. The pathobiology of vascular dementia[J]. Neuron, 2013, 80(4): 844-866.
[2]	Soares LM, Schiavon AP, Milani H, et al. Cognitive impairment and persistent anxiety-related responses following bilateral common carotid artery occlusion in mice[J]. Behav Brain Res, 2013, 249(7): 28-37.
[3]	Jiwa NS, Garrard P, Hainsworth AH. Experimental models of vascular dementia and vascular cognitive impairment: a systematic review[J]. J Neurochem, 2010, 115(4): 814-828.
[4]	Xi Y, Wang M, Zhang W, et al. Neuronal damage, central cholinergic dysfunction and oxidative damage correlate with cognitive deficits in rats with chronic cerebral hypoperfusion[J]. Neurobiol Learn Mem, 2014, 109(3): 7-19.
[5]	Mao X, Ji C, Sun C, et al. Topiramate attenuates cerebral ischemia/reperfusion injury in gerbils via activating GABAergic signaling and inhibiting astrogliosis[J]. Neurochem Int, 2012, 60(1): 39-46.
[6]	Cullen PK, Dulka BN, Ortiz S, et al. GABA-mediated presynaptic inhibition is required for precision of long-term memory[J]. Learn Mem, 2014, 21(4): 180-184.
[7]	Li CJ, Lu Y, Zhou M, et al. Activation of GABAB receptors ameliorates cognitive impairment via restoring the balance of HCN1/HCN2 surface expression in the hippocampal CA1 area in rats with chronic cerebral hypoperfusion[J]. Mol Neurobiol, 2014, 50(2): 704-720.
[8]	Caputi A, Melzer S, Michael M, et al. The long and short of GABAergic neurons[J]. Curr Opin in Neurobiol, 2013, 23(2): 179-186.
[9]	Lu Y, Li C, Zhou M, et al. Clonidine ameliorates cognitive impairment induced by chronic cerebral hypoperfusion via up-regulation of the GABABR1 and GAD67 in hippocampal CA1 in rats[J]. Pharmacol Biochem Behav, 2015, 132(1): 96-102.
[10]	Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1): 84-91.
[11]	Loreth D, Ozmen L, Revel FG, et al. Selective degeneration of septal and hippocampal GABAergic neurons in a mouse model of amyloidosis and tauopathy[J]. Neurobiol Dis, 2012, 47(1): 1-12.
[12]	Li G, Bien-Ly N, Andrews-Zwilling Y, et al. GABAergic interneuron dysfunction impairs hippocampal neurogenesis in adult apolipoprotein E4 knockin mice[J]. Cell Stem Cell, 2009, 5(6): 634-645.
[13]	Wang J, Fu X, Jiang C, et al. Bone marrow mononuclear cell transplantation promotes therapeutic angiogenesis via upregulation of the VEGF-VEGFR2 signaling pathway in a rat model of vascular dementia[J]. Behav Brain Res, 2014, 265(5): 171-180.
[14]	樊才瑞，刘卫平，龙乾发,等.骨髓间充质干细胞对血管性痴呆大鼠的保护作用[J].中华神经外科疾病研究杂志, 2015(2): 146-149.
[15]	王昌铭，李华信，姚永杰,等. BMSCs颈内动脉移植在VD大鼠脑内存活迁移及其对海马细胞凋亡的影响[J].免疫学杂志, 2014(3): 215-219.
[16]	井沆，田茂，董艳军,等.骨髓间充质干细胞移植对血管性痴呆大鼠认知功能及一氧化氮合酶的表达的影响[J].临床神经病学杂志, 2015(4): 276-280.
[17]	Taguchi A. Cell-based therapy for patients with vascular dementia[J]. Psychogeriatrics, 2011, 11(2): 113-115.
[18]	Long Q, Qiu B, Wang K, et al. Genetically engineered bone marrow mesenchymal stem cells improve functional outcome in a rat model of epilepsy[J]. Brain Res, 2013, 1532(3): 1-13.
[19]	Wang K, Long Q, Jia C, et al. Over-expression of Mash1 improves the GABAergic differentiation of bone marrow mesenchymal stem cells in vitro[J]. Brain Res Bull, 2013, 99(10): 84-94.
[20]	Mauri M, Lentini D, Gravati M, et al. Mesenchymal stem cells enhance GABAergic transmission in co-cultured hippocampal neurons[J]. Mol Cell Neurosci, 2012, 49(4): 395-405.

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