Knockdown of MicroRNA-1 in the Hippocampus Ameliorates Myocardial Infarction Induced Impairment of Long-Term Potentiation

Backgrounds/Aims: It has been reported that myocardial infarction (MI) is a risk factor for vascular dementia. However, the molecular mechanism remains largely unknown. Methods: MI mice were generated by ligation of the left coronary artery (LCA) for 4 weeks. Passive and active avoidance tests were performed to evaluate the cognitive ability of MI mice. A theta-burst stimulation (TBS) protocol was applied to elicit long-term potentiation (LTP) of the perforant pathway-dentate gyrus synapse (PP-DG). Western blot analysis was employed to assess protein levels. Results: In this study, we demonstrated that after 4 weeks of MI, C57BL/6 mice had significantly impaired memory. Compared with the sham group, in vivo physiological recording in the MI group revealed significantly decreased amplitude of population spikes (PS) with no effect on the latency and duration of the stimulus-response curve. The amplitude of LTP was markedly decreased in the MI group compared with the sham group. Further examination showed that the expression of the TBS-LTP-related proteins BDNF, GluA1 and phosphorylated GluA1 were all decreased in the MI group compared with those in the sham group. Strikingly, all these changes were prevented by hippocampal stereotaxic injection of an anti-miR-1 oligonucleotide fragment carried by a lentivirus vector (lenti-pre-AMO-1). Conclusion: MI induced cognitive decline and TBS-LTP impairment, and decreased BDNF and GluA1 phosphorylation levels from overexpression of miR-1ated were involved in this process.

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Faculty Opinions recommendation of Activity-induced long-term potentiation of excitatory synapses in developing zebrafish retina in vivo.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717956765.793461346 ◽

2012 ◽

Author(s):

David Zenisek ◽

Christina Joselevitch

Keyword(s):

Long Term Potentiation ◽

Excitatory Synapses ◽

Term Potentiation

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Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats

Current Neurovascular Research ◽

10.2174/1567202617666200514114917 ◽

2020 ◽

Vol 17 (4) ◽

pp. 354-360 ◽

Cited By ~ 1

Author(s):

Yu-Xing Ge ◽

Ying-Ying Lin ◽

Qian-Qian Bi ◽

Yu-Juan Chen

Keyword(s):

Synaptic Plasticity ◽

Temporal Lobe Epilepsy ◽

Synaptic Vesicle ◽

Long Term Potentiation ◽

Synaptic Dysfunction ◽

Over Expression ◽

Term Potentiation ◽

Synaptic Vesicle Protein 2A

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

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Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

Alzheimer s Research & Therapy ◽

10.1186/s13195-021-00860-1 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Maria Mensch ◽

Jade Dunot ◽

Sandy M. Yishan ◽

Samuel S. Harris ◽

Aline Blistein ◽

...

Keyword(s):

Neuronal Activity ◽

Ex Vivo ◽

Long Term Potentiation ◽

Network Activity ◽

Strongly Correlated ◽

App Processing ◽

Term Potentiation ◽

Hippocampal Network

Abstract Background Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.

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