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

2020 ◽  
Vol 17 (4) ◽  
pp. 354-360 ◽  
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.

Nicotine Enhances the Depressive Actions of Aβ1–40 on Long-Term Potentiation in the Rat Hippocampal CA1 Region In Vivo

2003 ◽  
Vol 89 (6) ◽  
pp. 2917-2922 ◽  
Author(s):  
D. B. Freir ◽  
C. E. Herron
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
High Affinity ◽  
Ca1 Region ◽  
Α7 Nachr ◽  
Term Potentiation ◽  
Significant Depression

Hippocampal long-term potentiation (LTP) is a form of synaptic plasticity used as a cellular model of memory. Beta amyloid (Aβ) is involved in Alzheimer's disease (AD), a neurode-generative disorder leading to cognitive deficits. Nicotine is also claimed to act as a cognitive enhancer. Aβ is known to bind with high affinity to the α7-nicotinic acetylcholine receptor (nAChR). Here we have investigated the effect of intracerebroventricular (icv) injection of the endogenous peptide Aβ1–40 on LTP in area CA1 of urethananesthetized rats. We also examined the effect of Aβ12–28 (icv), which binds with high affinity to the α7-nAChR and the specific α7-nAChR antagonist methyllycaconitine (MLA) on LTP. We found that Aβ12–28 had no effect on LTP, whereas MLA depressed significantly LTP, suggesting that activation of the α7-nAChR is a requirement for LTP. Within the in vivo environment, where other factors may compete with Aβ12–28 for binding to α7-nAChR, it does not appear to modulate LTP. To determine if the depressive action of Aβ1–40 on LTP could be modulated by nicotine, these agents were also co-applied. Injection of 1 or 10 nmol Aβ1–40 caused a significant depression of LTP, whereas nicotine alone (3 mg/kg) had no effect on LTP. Co-injection of nicotine with Aβ1–40 1 h prior to LTP induction caused a further significant depression of LTP compared with Aβ1–40 alone. These results demonstrate that nicotine enhances the deficit in LTP produced by Aβ1–40. This then suggests that nicotine may exacerbate the depressive actions of Aβ on synaptic plasticity in AD.

scholarly journals Widespread promoter methylation of synaptic plasticity genes in long-term potentiation in the adult brain in vivo

BMC Genomics ◽  
2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Jesper L. V. Maag ◽  
Dominik C. Kaczorowski ◽  
Debabrata Panja ◽  
Timothy J. Peters ◽  
Clive R. Bramham ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Promoter Methylation ◽  
Long Term Potentiation ◽  
Adult Brain ◽  
Term Potentiation

scholarly journals Simvastatin Impairs Hippocampal Synaptic Plasticity and Cognitive Function in Mice

2021 ◽  
Author(s):  
Yujun Guo ◽  
Guichang Zou ◽  
Keke Qi ◽  
Jin Jin ◽  
Lei Yao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Memory Function ◽  
Long Term Potentiation ◽  
Drug Discontinuation ◽  
Cholesterol Levels ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation ◽  
The Central Nervous System

Abstract Lipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive

scholarly journals Effects of the hydroalcoholic extract of Rosa damascena on hippocampal long-term potentiation in rats fed high-fat diet

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Seyed Asaad Karimi ◽  
Somayeh Komaki ◽  
Masoumeh Taheri ◽  
Ghazaleh Omidi ◽  
Masoumeh Kourosh-Arami ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Rosa Damascena ◽  
High Fat ◽  
Oxidative Stress Biomarkers ◽  
Hydroalcoholic Extract ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation

AbstractHigh-fat diets (HFDs) and obesity can cause serious health problems, such as neurodegenerative diseases and cognitive impairments. Consumption of HFD is associated with reduction in hippocampal synaptic plasticity. Rosa damascena (R. damascena) is traditionally used as a dietary supplement for many disorders. This study was carried out to determine the beneficial effect of hydroalcoholic extract of R. damascena on in vivo hippocampal synaptic plasticity (long-term potentiation, LTP) in the perforant pathway (PP)—dentate gyrus (DG) pathway in rats fed with an HFD. Male Wistar rats were randomly assigned to four groups: Control, R. damascena extract (1 g/kg bw daily for 30 days), HFD (for 90 days) and HFD + extract. The population spike (PS) amplitude and slope of excitatory post-synaptic potentials (EPSP) were measured in DG area in response to stimulation applied to the PP. Serum oxidative stress biomarkers [total thiol group (TTG) and superoxide dismutase (SOD)] were measured. The results showed the HFD impaired LTP induction in the PP-DG synapses. This conclusion is supported by decreased EPSP slope and PS amplitude of LTP. R. damascena supplementation in HFD animals enhanced EPSP slope and PS amplitude of LTP in the granular cell of DG. Consumption of HFD decreased TTG and SOD. R. damascena extract consumption in the HFD animals enhanced TTG and SOD. These data indicate that R. damascena dietary supplementation can ameliorate HFD-induced alteration of synaptic plasticity, probably through its significant antioxidant effects and activate signalling pathways, which are critical in controlling synaptic plasticity.

scholarly journals Coincidence of cholinergic pauses, dopaminergic activation and depolarization drives synaptic plasticity in the striatum

2019 ◽  
Author(s):  
Yan-Feng Zhang ◽  
Simon D. Fisher ◽  
Manfred Oswald ◽  
Jeffery R. Wickens ◽  
John N. J. Reynolds
Keyword(s):  
Synaptic Plasticity ◽  
Reinforcement Learning ◽  
Long Term Potentiation ◽  
Dopamine Neurons ◽  
Projection Neurons ◽  
Cholinergic Interneurons ◽  
Term Potentiation ◽  
Phasic Activation

AbstractPauses in the firing of tonically-active cholinergic interneurons (ChIs) in the striatum coincide with phasic activation of dopamine neurons during reinforcement learning. However, how this pause influences cellular substrates of learning is unclear. Using two in vivo paradigms, we report that long-term potentiation (LTP) at corticostriatal synapses with spiny projection neurons (SPNs) is dependent on the temporal coincidence of ChI pause and dopamine phasic activation, critically accompanied by SPN depolarization.

scholarly journals Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yujun Guo ◽  
Guichang Zou ◽  
Keke Qi ◽  
Jin Jin ◽  
Lei Yao ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Memory Function ◽  
Long Term Potentiation ◽  
Drug Discontinuation ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation ◽  
The Central Nervous System

AbstractLipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive function impairment, caused by long-term usage of BBB-permeable statins.

scholarly journals Simvastatin Impairs Hippocampal Synaptic Plasticity and Cognitive Function in Mice

2020 ◽  
Author(s):  
Yujun Guo ◽  
Guichang Zou ◽  
Jin Jin ◽  
Lei Yao ◽  
Keke Qi ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Function ◽  
Memory Function ◽  
Long Term Potentiation ◽  
Drug Discontinuation ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation ◽  
The Central Nervous System

Abstract Lipophilic statins which are blood brain barrier (BBB) permeable are speculated to affect the cholesterol synthesis and neural functions in the central nervous system. However, whether these statins can affect cholesterol levels and synaptic plasticity in hippocampus and the in vivo consequence remain unclear. Here, we report that long-term subcutaneous treatments of simvastatin significantly impair mouse hippocampal synaptic plasticity, reflected by the attenuated long-term potentiation of field excitatory postsynaptic potentials. The simvastatin administration causes a deficiency in recognition and spatial memory but fails to affect motor ability and anxiety behaviors in the mice. Mass spectrometry imaging indicates a significant decrease in cholesterol intensity in hippocampus of the mice receiving chronic simvastatin treatments. Such effects of simvastatin are transient because drug discontinuation can restore the hippocampal cholesterol level and synaptic plasticity and the memory function. These findings may provide further clues to elucidate the mechanisms of neurological side effects, especially the brain cognitive function impairment, caused by long-term usage of BBB-permeable statins.

scholarly journals Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo

2019 ◽  
Author(s):  
Cleiton Lopes-Aguiar ◽  
Rafael N. Ruggiero ◽  
Matheus T. Rossignoli ◽  
Ingrid de Miranda Esteves ◽  
José Eduardo Peixoto Santos ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Plasticity ◽  
Animal Models ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
High Frequency Stimulation ◽  
Evoked Responses ◽  
Term Potentiation

ABSTRACTN-methyl-D-aspartate receptor (NMDAr) antagonists such as ketamine (KET) produce psychotic-like behavior in both humans and animal models. NMDAr hypofunction affects normal oscillatory dynamics and synaptic plasticity in key brain regions related with schizophrenia, particularly in the hippocampus and the prefrontal cortex. In contrast, long-term potentiation (LTP) induction is known to increase glutamatergic transmission. Thus, we hypothesized that LTP could mitigate the electrophysiological changes promoted by KET. We recorded HPC-PFC local field potentials and evoked responses in urethane anesthetized rats, before and after KET administration, preceded or not by LTP induction. Our results show that KET promotes an aberrant delta-high-gamma crossfrequency coupling in the PFC and an enhancement in HPC-PFC evoked responses. LTP induction prior to KET attenuates changes in synaptic efficiency and prevents the increase in cortical gamma amplitude comodulation. These findings are consistent with evidence that increased efficiency of glutamatergic receptors attenuates cognitive impairment in animal models of psychosis. Therefore, high-frequency stimulation in HPC may be a useful tool to better understand how to prevent NMDAr hypofunction effects on synaptic plasticity and oscillatory coordination in cortico-limbic circuits.

scholarly journals Numerical Simulation: Fluctuation in Background Synaptic Activity Regulates Synaptic Plasticity

2021 ◽  
Vol 15 ◽  
Author(s):  
Yuto Takeda ◽  
Katsuhiko Hata ◽  
Tokio Yamazaki ◽  
Masaki Kaneko ◽  
Osamu Yokoi ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Statistical Fluctuation ◽  
Noisy Environment ◽  
Term Potentiation ◽  
Synapse Model ◽  
The Brain

Synaptic plasticity is vital for learning and memory in the brain. It consists of long-term potentiation (LTP) and long-term depression (LTD). Spike frequency is one of the major components of synaptic plasticity in the brain, a noisy environment. Recently, we mathematically analyzed the frequency-dependent synaptic plasticity (FDP) in vivo and found that LTP is more likely to occur with an increase in the frequency of background synaptic activity. Meanwhile, previous studies suggest statistical fluctuation in the amplitude of background synaptic activity. Little is understood, however, about its contribution to synaptic plasticity. To address this issue, we performed numerical simulations of a calcium-based synapse model. Then, we found attenuation of the tendency to become LTD due to an increase in the fluctuation of background synaptic activity, leading to an enhancement of synaptic weight. Our result suggests that the fluctuation affects synaptic plasticity in the brain.

scholarly journals Functional MRI of long-term potentiation: imaging network plasticity

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130152 ◽  
Author(s):  
Efrén Álvarez-Salvado ◽  
Vicente Pallarés ◽  
Andrea Moreno ◽  
Santiago Canals
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Plastic Property ◽  
Cellular Level ◽  
Synaptic Activity ◽  
Long Term Memory ◽  
Cellular Mechanisms ◽  
Term Potentiation

Neurons are able to express long-lasting and activity-dependent modulations of their synapses. This plastic property supports memory and conveys an extraordinary adaptive value, because it allows an individual to learn from, and respond to, changes in the environment. Molecular and physiological changes at the cellular level as well as network interactions are required in order to encode a pattern of synaptic activity into a long-term memory. While the cellular mechanisms linking synaptic plasticity to memory have been intensively studied, those regulating network interactions have received less attention. Combining high-resolution fMRI and in vivo electrophysiology in rats, we have previously reported a functional remodelling of long-range hippocampal networks induced by long-term potentiation (LTP) of synaptic plasticity in the perforant pathway. Here, we present new results demonstrating an increased bilateral coupling in the hippocampus specifically supported by the mossy cell commissural/associational pathway in response to LTP. This fMRI-measured increase in bilateral connectivity is accompanied by potentiation of the corresponding polysynaptically evoked commissural potential in the contralateral dentate gyrus and depression of the inactive convergent commissural pathway to the ipsilateral dentate. We review these and previous findings in the broader context of memory consolidation.

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