CAO Yanjing,WU Jiali,LI Peng, et al. The expression analysis of transmitter related vesicle transporters of hippocampal in CCI induced-vascular dementia rats[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2018, 48(11): 801-806,812.
Abstract:Objective: To investigate the expression of different vesicles transporter (different synapses) vGluTs, vAChT and vGAT in the hippocampal CA1-3 region in rats with chronic global cerebral ischemia. Methods: VaD animal model was established by BCCAO method, Western blot and immunofluorescence were used to detect the expression of vGluTs, vAChT and vGAT in hippocampal CA1-3. Results: In the Morris test, the escape latency of VaD rats was significantly extended compared with sham and control animals (P<0.05). The percentage of searching time in the VaD group was significantly reduced (P<0.05) and the searching distance in target quadrant was significantly decreased (P<0.01). In the T-maze test: the error rate of the delayed operation of VaD rats was significantly increased (P<0.01). The levels of vGluT1 and vGluT3 in the hippocampal CA1-3 region of VaD rats were significantly lower than those in the sham and control groups (P<0.01). Compared with the sham and control groups, the expression of vAChT in the hippocampal CA1-3 region of VaD rats was decreased (P<0.01). Compared with sham and control groups, the number of vGluT1 and vGluT3 positive neurons in VaD rats decreased in hippocampal CA1-3 region, and the number of vAChT positive neurons in hippocampal CA1-3 was also significantly decreased (P<0.01). Conclusion: Glutamate, cholinergic vesicle cargo function defects, glutamate, central cholinergic neurotransmitter imbalance, neuronal loss, CA1-CA3 hippocampus information loop destruction is the main cause of cognitive dysfunction in rats under the ischemic conditions.
[1] AULD D S, KORNECOOK T J, BASTIANETTO S, et al. Alzheimer’s disease and the basal forebrain cholinergic system: relations to beta-amyloid peptides, cognition, and treatment strategies[J]. Prog Neurobiol, 2002, 68(3): 209-245.
[2] FREMEAU R T JR, VOGLMAIER S, SEAL R P, et al. VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate[J]. Trends Neurosci, 2004, 27(2): 98-103.
[3] ARVIDSSON U, RIEDL M, ELDE R, et al. Vesicular acetylcholine transporter (VAChT) protein: a novel and unique marker for cholinergic neurons in the central and peripheral nervous systems[J]. J Comp Neurol, 1997, 378(4): 454-467.
[4] ODA Y. Choline acetyltransferase: The structure, distribution and pathologic changes in the central nervous system[J]. Pathol Int, 1999, 49(11): 921-937.
[5] PARLE M, SINGH N. Reversal of memory deficits by Atorvastatin and Simvastatin in rats[J]. Yakugaku Zasshi, 2007, 127(7): 1125-1137.
[6] ZHANG T, WANG W, HUANG J, et al. Metabolomic investigation of regional brain tissue dysfunctions induced by global cerebral ischemia[J]. BMC Neurosci, 2016, 17(1): 1-11.
[7] ZHAO R R, XU F, XU X C, et al. Effects of alpha-lipoic acid on spatial learning and memory, oxidative stress, and central cholinergic system in a rat model of vascular dementia[J]. Neurosci Lett, 2015, 587: 113-119.
[8] ROSENBAUM R S, PRISELAC S, KÖHLER S, et al. Remote spatial memory in an amnesic person with extensive bilateral hippocampal lesions[J]. Nat Neurosci, 2000, 3(10): 1044-1048.
[9] SIKSOU L, SILM K, BIESEMANN C, et al. A role for vesicular glutamate transporter 1 in synaptic vesicle clustering and mobility[J]. Eur J Neurosci, 2013, 37(10): 1631-1642.
[10] MÜNSTERWANDOWSKI A, ZANDER J F, RICHTER K, et al. Co-existence of functionally different vesicular neurotransmitter transporters[J]. Front Synaptic Neurosci, 2016, 8: 4.
[11] WOOTZ H, FITZSIMONSKANTAMNENI E, LARHAMMAR M, et al. Alterations in the motor neuron-Renshaw cell circuit in the Sod1G93A mouse model[J]. Comp Neurol, 2013, 521(7): 1449-1469.
[12] SEAL R P, EDWARDS R H. Functional implications of neurotransmitter co-release: glutamate and GABA share the load [J]. Curr Opin Pharmacol, 2006, 6(1): 114-119.
[13] KLJAKIC O, JANICKOVA H, PRADO V F, et al. Cholinergic/glutamatergic co-transmission in striatal cholinergic interneurons: new mechanisms regulating striatal computation[J]. J Neurochem, 2017, 142 Suppl 2: 90-102.
[14] KEMPPAINEN S, HÄMÄLÄINEN E, MIETTINEN P O,
et al. Behavioral and neuropathological consequences of transient global ischemia in APP/PS1 Alzheimer model mice [J]. Behav Brain Res, 2014, 275: 15-26.
[15] GEMMELL E, BOSOMWORTH H, ALLAN L, et al. Hippocampal neuronal atrophy and cognitive function in delayed poststroke and aging-related dementias[J]. Stroke, 2012, 43(3): 808-814.