Low-Level Inhibition of GABAergic Synapses Enhances Gene Expressions Crucial for Neuronal Plasticity in the Hippocampus After Ischemic Stroke.

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Tytuł:: Low-Level Inhibition of GABAergic Synapses Enhances Gene Expressions Crucial for Neuronal Plasticity in the Hippocampus After Ischemic Stroke.
Autorzy:: Okamura M; Graduate School of Health Sciences, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo 060-0812, Japan. Electronic address: .
Inoue T; Graduate School of Health Sciences, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo 060-0812, Japan; Research Fellow of Japan Society for the Promotion of Science, 5-3-1 Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan. Electronic address: .
Takamatsu Y; Department of Rehabilitation Science, Faculty of Health Sciences, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo 060-0812, Japan. Electronic address: .
Maejima H; Department of Rehabilitation Science, Faculty of Health Sciences, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo 060-0812, Japan. Electronic address: .
Źródło:: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association [J Stroke Cerebrovasc Dis] 2020 Dec; Vol. 29 (12), pp. 105316. Date of Electronic Publication: 2020 Sep 28.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: Philadelphia, PA : Saunders
Original Publication: New York, NY : Demos Publications, [1991-
MeSH Terms:: Bicuculline/*pharmacology
GABA-A Receptor Antagonists/*pharmacology
GABAergic Neurons/*drug effects
Hippocampus/*drug effects
Infarction, Middle Cerebral Artery/*drug therapy
Infarction, Middle Cerebral Artery/*genetics
Neural Inhibition/*drug effects
Neuronal Plasticity/*drug effects
Synaptic Transmission/*drug effects
Animals ; Brain-Derived Neurotrophic Factor/genetics ; Brain-Derived Neurotrophic Factor/metabolism ; Disease Models, Animal ; Disks Large Homolog 4 Protein/genetics ; Disks Large Homolog 4 Protein/metabolism ; GABAergic Neurons/metabolism ; GABAergic Neurons/pathology ; Gene Expression Regulation ; Hippocampus/metabolism ; Hippocampus/pathology ; Hippocampus/physiopathology ; Infarction, Middle Cerebral Artery/metabolism ; Infarction, Middle Cerebral Artery/physiopathology ; Male ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Rats, Sprague-Dawley ; Receptor, trkB/genetics ; Receptor, trkB/metabolism ; Receptors, Growth Factor/genetics ; Receptors, Growth Factor/metabolism ; Synaptophysin/genetics ; Synaptophysin/metabolism
Contributed Indexing:: Keywords: GABA; Hippocampus; Neurotrophin; Stroke
Substance Nomenclature:: 0 (Bdnf protein, rat)
0 (Brain-Derived Neurotrophic Factor)
0 (Disks Large Homolog 4 Protein)
0 (Dlg4 protein, rat)
0 (GABA-A Receptor Antagonists)
0 (Nerve Tissue Proteins)
0 (Receptors, Growth Factor)
0 (Synaptophysin)
0 (Syp protein, rat)
136958-07-1 (Ngfr protein, rat)
EC 2.7.10.1 (Ntrk2 protein, rat)
EC 2.7.10.1 (Receptor, trkB)
Y37615DVKC (Bicuculline)
Entry Date(s):: Date Created: 20200929 Date Completed: 20201208 Latest Revision: 20201214
Update Code:: 20240105
DOI:: 10.1016/j.jstrokecerebrovasdis.2020.105316
PMID:: 32992173
: Czasopismo naukowe

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Objective: Pharmacological inhibition of GABAergic synapses could represent a potent neuromodulation strategy to activate hippocampal neurons and increase neurotrophic factor gene expression, thus exerting a beneficial effect on post-stroke cognitive impairment (PSCI). The objective of this study was to assess the effects of low-level inhibition of GABAergic synapses on hippocampal gene expressions related to neuroplasticity using the middle cerebral artery occlusion surgery (MCAO) ischemic stroke rat model.
Methods: The animals were randomly assigned to three experimental groups-(1) a sham operated group (SHAM), (2) a control group (CON), and (3) a bicuculline group (BIC). MCAO was performed in the CON and BIC groups. A non-epileptic dose of bicuculline (0.25 mg/kg) was intraperitoneally administered every day for two weeks, starting three days after surgery, to the rats in the BIC group. The mRNA expression of brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), in relation to neurotrophic intracellular signal, p75, in relation to apoptosis, and synaptophysin (SYP) and PSD-95, synaptic markers, were assessed in the hippocampus ipsilateral to the ischemic site.
Results: MCAO increased the gene expression of TrkB. Furthermore, MCAO plus bicuculline administration increased the expression ratio of TrkB to p75 and SYP gene expression.
Conclusion: Therefore, this study showed that administration of bicuculline after stroke beneficially modulated the expression of crucial genes for neuroplasticity, including BDNF receptors and SYP, in the ipsilateral hippocampus, suggesting that low-level inhibition of GABAergic synapses could lead to beneficial neuromodulation in the hippocampus after stroke.
(Copyright © 2020 Elsevier Inc. All rights reserved.)

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