Abstract
Objective: Synaptic plasticity is critical for neurorehabilitation after focal cerebral ischemia. Connexin 43 (Cx43), the main component of the gap junction, has been shown to be pivotal for synaptic plasticity. The objective of this study was to investigate the role of the Cx43 inhibitor (Gap26) and gap junction modifier (GAP-134) in neurorehabilitation and to study their contribution to synaptic plasticity after focal ischemia.Methods: Time course expression of both total and phosphorylated Cx43 (p-Cx43) were detected by western blotting at 3, 7, and 14 d after focal ischemia. Gap26 and GAP-134 were administered starting from 3 d post focal ischemia. Neurological performances were evaluated by balance beam walking test and Y-maze test at 1, 3, and 7 d. Golgi staining and transmission electron microscope (TEM) detection were conducted at 7 d for observing dendritic spine numbers and synaptic ultrastructure, respectively. Immunofluorescent staining was used at 7 d for detection of synaptic plasticity markers, including synaptophysin (SYN) and growth-associated protein-43 (GAP-43).Results: Expression levels of both total Cx43 and p-Cx43 were increased after focal cerebral ischemia, peaking at 7 d. Compared with the MCAO group, Gap26 worsened the neurological behavior and decreased the dendritic spine number while GAP-134 improved the neurobehavior and increased the number of dendritic spines. Moreover, Gap26 further destroyed the synaptic structure, concomitant with downregulated SYN and GAP-43, whereas GAP-134 alleviated synaptic destruction and upregulated SYN and GAP-43.Conclusion: These findings suggested that Cx43 or the gap junction was involved in synaptic plasticity, thereby promoting neural recovery after ischemic stroke. Treatments enhancing gap junctions may be potential promising therapeutic measures for neurorehabilitation after ischemic stroke.
Highlights
Ischemic stroke is a worldwide leading cause for morbidity, mortality, and disability
For the balance beam walking test, scores for the Middle Cerebral Artery Occlusion (MCAO) group, Gap26 group, and GAP-134 group were all dramatically higher when compared with the sham group at 1 d (P < 0.05, Figure 2A)
Due to drug treatments just beginning from 3 d, no wonder no difference existed between the MCAO group and the Gap26/GAP-134 group at 3 d after focal ischemia (P > 0.05, Figure 2A)
Summary
Ischemic stroke is a worldwide leading cause for morbidity, mortality, and disability. Cx43 Promoted Synaptic Plasticity corresponding burdens, treatments for promoting neural function during the subacute phase is worth exploring more. The key molecular basis of neural function after cerebral ischemia is synaptic plasticity [2]. Synaptic plasticity refers to a reparative process and contributes to improvement of neurological behavior. Numerous treatments which promoted synaptic plasticity have been demonstrated to be protective against ischemic injury. Exercise training has been reported to enhance synaptic plasticity and thereby promote rehabilitation after ischemic stroke [3]. If the potential molecular mechanisms of synaptic plasticity can be elucidated, it will trigger the appearance of many effective measures for treating ischemic stroke patients to improve their neurological behavior. There is a great need to investigate the mechanisms underlying synaptic plasticity after cerebral ischemia
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