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Meanwhile, synaptic pathology plays a prominent role in the initial stage of AD and VaD. However, whether and how CBH impairs presynaptic plasticity is currently unclear.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In the present study, we performed a battery of techniques, including primary neuronal culture, patch clamp, stereotaxic injection of the lentiviral vectors, morris water maze (MWM), dual luciferase reporter assay, FM1\u201343 fluorescence dye evaluation, qRT-PCR and western blot, to investigate the regulatory effect of <jats:italic>miR-153<\/jats:italic> on hippocampal synaptic vesicle release both in vivo and in vitro. The CBH rat model was generated by bilateral common carotid artery ligation (2VO).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Compared to sham rats, 2VO rats presented decreased field excitatory postsynaptic potential (fEPSP) amplitude and increased paired-pulse ratios (PPRs) in the CA3-CA1 pathway, as well as significantly decreased expression of multiple vesicle fusion-related proteins, including SNAP-25, VAMP-2, syntaxin-1A and synaptotagmin-1, in the hippocampi. The levels of <jats:italic>microRNA-153<\/jats:italic> (<jats:italic>miR-153<\/jats:italic>) were upregulated in the hippocampi of rats following 2VO surgery, and in the plasma of dementia patients. The expression of the vesicle fusion-related proteins affected by 2VO was inhibited by <jats:italic>miR-153<\/jats:italic>, elevated by <jats:italic>miR-153<\/jats:italic> inhibition, and unchanged by binding-site mutation or miR masks. FM1\u201343 fluorescence images showed that <jats:italic>miR-153<\/jats:italic> blunted vesicle exocytosis, but this effect was prevented by either 2\u2032-<jats:italic>O<\/jats:italic>-methyl antisense oligoribonucleotides to <jats:italic>miR-153<\/jats:italic> (AMO-153) and miR-masking of the <jats:italic>miR-153<\/jats:italic> binding site in the 3\u2032 untranslated region (3\u2019UTR) of the <jats:italic>Snap25, Vamp2, Stx1a<\/jats:italic> and <jats:italic>Syt1<\/jats:italic> genes. Overexpression of <jats:italic>miR-153<\/jats:italic> by lentiviral vector-mediated <jats:italic>miR-153<\/jats:italic> mimics (lenti-pre-<jats:italic>miR-153<\/jats:italic>) decreased the fEPSP amplitude and elevated the PPR in the rat hippocampus, whereas overexpression of the antisense molecule (lenti-AMO-<jats:italic>153<\/jats:italic>) reversed these changes triggered by 2VO. Furthermore, lenti-AMO-<jats:italic>153<\/jats:italic> attenuated the cognitive decline of 2VO rats.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Overexpression of <jats:italic>miR-153<\/jats:italic> controls CBH-induced presynaptic vesicle release impairment by posttranscriptionally regulating the expression of four vesicle release-related proteins by targeting the 3\u2019UTRs of the <jats:italic>Stx1a<\/jats:italic>, <jats:italic>Snap25<\/jats:italic>, <jats:italic>Vamp2<\/jats:italic> and <jats:italic>Syt1<\/jats:italic> genes. These findings identify a novel mechanism of presynaptic plasticity impairment during CBH, which may be a new drug target for prevention or treatment of AD and VaD.<\/jats:p>\n                \n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s12964-020-00551-8","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T17:03:28Z","timestamp":1586192608000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["MicroRNA-153 impairs presynaptic plasticity by blocking vesicle release following chronic brain hypoperfusion"],"prefix":"10.1186","volume":"18","author":[{"given":"Mei-Ling","family":"Yan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Mei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Nan","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Yu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Jing","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Bin","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandan","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Hua","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"551_CR1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3233\/JAD-180004","volume":"63","author":"J de la Torre","year":"2018","unstructured":"de la Torre J. 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