scholarly journals Citalopram Ameliorates Impairments in Spatial Memory and Synaptic Plasticity in Female 3xTgAD Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Zhang Wei ◽  
Guo Junhong ◽  
Niu Xiaoyuan ◽  
Wang Jie ◽  
Wang Zhaojun ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Memory ◽  
Antidepressant Drug ◽  
Amyloid Plaques ◽  
Long Term Potentiation ◽  
Memory Deficit ◽  
Behavioral Performance ◽  
Promising Strategy ◽  
Term Potentiation

Alzheimer’s disease (AD) is the primary cause of dementia. There is no effective treatment. Amyloid-β peptide (Aβ) plays an important role in the pathogenesis and thus strategies suppressing Aβ production and accumulation seem promising. Citalopram is an antidepressant drug and can decrease Aβ production and amyloid plaques in transgenic mice of AD and humans. Whether citalopram can ameliorate memory deficit was not known yet. We tested the effects of citalopram on behavioral performance and synaptic plasticity in female 3xTgAD mice, a well-characterized model of AD. Mice were treated with citalopram or water from 5 months of age for 3 months. Citalopram treatment at approximately 10 mg/kg/day significantly improved spatial memory in the Morris water maze (MWM) test, while not affecting anxiety-like and depression-like behavior in 3xTgAD mice. Further, hippocampal long-term potentiation (LTP) impairment in 3xTgAD mice was reversed by citalopram treatment. Citalopram treatment also significantly decreased the levels of insoluble Aβ40 in hippocampal and cortical tissues in 3xTgAD mice, accompanied with a reduced amyloid precursor protein (APP). Together, citalopram treatment may be a promising strategy for AD and further clinical trials should be conducted to verify the effect of citalopram on cognition in patients with AD or mild cognitive impairment.

scholarly journals Embelin Improves the Spatial Memory and Hippocampal Long-Term Potentiation in a Rat Model of Chronic Cerebral Hypoperfusion

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Saatheeyavaane Bhuvanendran ◽  
Siti Najmi Syuhadaa Bakar ◽  
Yatinesh Kumari ◽  
Iekhsan Othman ◽  
Mohd. Farooq Shaikh ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Memory ◽  
Rat Model ◽  
Long Term Potentiation ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Mrna Levels ◽  
Post Surgery ◽  
Term Potentiation

Abstract Alzheimer’s disease (AD) is the second most occurring neurological disorder after stroke and is associated with cerebral hypoperfusion, possibly contributing to cognitive impairment. In the present study, neuroprotective and anti-AD effects of embelin were evaluated in chronic cerebral hypoperfusion (CCH) rat model using permanent bilateral common carotid artery occlusion (BCCAO) method. Rats were administered with embelin at doses of 0.3, 0.6 or 1.2 mg/kg (i.p) on day 14 post-surgery and tested in Morris water maze (MWM) followed by electrophysiological recordings to access cognitive abilities and synaptic plasticity. The hippocampal brain regions were extracted for gene expression and neurotransmitters analysis. Treatment with embelin at the doses of 0.3 and 0.6 mg/kg significantly reversed the spatial memory impairment induced by CCH in rats. Embelin treatment has significantly protected synaptic plasticity impairment as assessed by hippocampal long-term potentiation (LTP) test. The mechanism of this study demonstrated that embelin treatment alleviated the decreased expression of BDNF, CREB1, APP, Mapt, SOD1 and NFκB mRNA levels caused by CCH rats. Furthermore, treatment with embelin demonstrated neuromodulatory activity by its ability to restore hippocampal neurotransmitters. Overall these data suggest that embelin improve memory and synaptic plasticity impairment in CCH rats and can be a potential drug candidate for neurodegenerative disease-related cognitive disorders.

scholarly journals Alpha-synuclein is involved in manganese-induced spatial memory and synaptic plasticity impairments via TrkB/Akt/Fyn-mediated phosphorylation of NMDA receptors

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Zhuo Ma ◽  
Kuan Liu ◽  
Xin-Ru Li ◽  
Can Wang ◽  
Chang Liu ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Memory ◽  
Long Term Potentiation ◽  
Alpha Synuclein ◽  
Ht22 Cells ◽  
Protein Levels ◽  
Trkb Receptors ◽  
Term Potentiation

Abstract Manganese (Mn) overexposure produces long-term cognitive deficits and reduces brain-derived neurotrophic factor (BDNF) in the hippocampus. However, it remains elusive whether Mn-dependent enhanced alpha-synuclein (α-Syn) expression, suggesting a multifaceted mode of neuronal toxicities, accounts for interference with BDNF/TrkB signaling. In this study, we used C57BL/6J WT and α-Syn knockout (KO) mice to establish a model of manganism and found that Mn-induced impairments in spatial memory and synaptic plasticity were related to the α-Syn protein. In addition, consistent with the long-term potentiation (LTP) impairments that were observed, α-Syn KO relieved Mn-induced degradation of PSD95, phosphorylated CaMKIIα, and downregulated SynGAP protein levels. We transfected HT22 cells with lentivirus (LV)-α-Syn shRNA, followed by BDNF and Mn stimulation. In vitro experiments indicated that α-Syn selectively interacted with TrkB receptors and inhibited BDNF/TrkB signaling, leading to phosphorylation and downregulation of GluN2B. The binding of α-Syn to TrkB and Fyn-mediated phosphorylation of GluN2B were negatively regulated by BDNF. Together, these findings indicate that Mn-dependent enhanced α-Syn expression contributes to further exacerbate BDNF protein-level reduction and to inhibit TrkB/Akt/Fyn signaling, thereby disturbing Fyn-mediated phosphorylation of the NMDA receptor GluN2B subunit at tyrosine. In KO α-Syn mice treated with Mn, spatial memory and LTP impairments were less pronounced than in WT mice. However, the same robust neuronal death was observed as a result of Mn-induced neurotoxicity.

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.

Prenatal stress in rats attenuates hippocampal long-term potentiation and induces deficits in synaptic plasticity

2006 ◽  
Vol 16 ◽  
pp. S52
Author(s):  
S. Salomon ◽  
Y. Nachum-Biala ◽  
Y. Bogush ◽  
M. Lineal ◽  
H. Matzner ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Prenatal Stress ◽  
Long Term Potentiation ◽  
Term Potentiation

scholarly journals Synaptic plasticity-dependent competition rule influences memory formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yire Jeong ◽  
Hye-Yeon Cho ◽  
Mujun Kim ◽  
Jung-Pyo Oh ◽  
Min Soo Kang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Fear Conditioning ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Specific Pattern ◽  
Memory Encoding ◽  
Competition Rule ◽  
Term Potentiation ◽  
Input Activity

AbstractMemory is supported by a specific collection of neurons distributed in broad brain areas, an engram. Despite recent advances in identifying an engram, how the engram is created during memory formation remains elusive. To explore the relation between a specific pattern of input activity and memory allocation, here we target a sparse subset of neurons in the auditory cortex and thalamus. The synaptic inputs from these neurons to the lateral amygdala (LA) are not potentiated by fear conditioning. Using an optogenetic priming stimulus, we manipulate these synapses to be potentiated by the learning. In this condition, fear memory is preferentially encoded in the manipulated cell ensembles. This change, however, is abolished with optical long-term depression (LTD) delivered shortly after training. Conversely, delivering optical long-term potentiation (LTP) alone shortly after fear conditioning is sufficient to induce the preferential memory encoding. These results suggest a synaptic plasticity-dependent competition rule underlying memory formation.

scholarly journals Long-term potentiation is independent of the C-tail of the GluA1 AMPA receptor subunit

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Javier Díaz-Alonso ◽  
Wade Morishita ◽  
Salvatore Incontro ◽  
Jeffrey Simms ◽  
Julia Holtzman ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Morris Water Maze ◽  
Ampa Receptor ◽  
Water Maze ◽  
Long Term Potentiation ◽  
Receptor Subunit ◽  
Terminal Domain ◽  
Term Potentiation ◽  
Ampa Receptor Subunit

We tested the proposal that the C-terminal domain (CTD) of the AMPAR subunit GluA1 is required for LTP. We found that a knock-in mouse lacking the CTD of GluA1 expresses normal LTP and spatial memory, assayed by the Morris water maze. Our results support a model in which LTP generates synaptic slots, which capture passively diffusing AMPARs.

scholarly journals Phosphorylation of the AMPAR-TARP Complex in Synaptic Plasticity

Proteomes ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 40 ◽  
Author(s):  
Joongkyu Park
Keyword(s):  
Synaptic Plasticity ◽  
Drug Addiction ◽  
Ampa Receptor ◽  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Regulatory Proteins ◽  
Cellular Models ◽  
Brain Functions ◽  
Term Potentiation

Synaptic plasticity has been considered a key mechanism underlying many brain functions including learning, memory, and drug addiction. An increase or decrease in synaptic activity of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) complex mediates the phenomena as shown in the cellular models of synaptic plasticity, long-term potentiation (LTP), and depression (LTD). In particular, protein phosphorylation shares the spotlight in expressing the synaptic plasticity. This review summarizes the studies on phosphorylation of the AMPAR pore-forming subunits and auxiliary proteins including transmembrane AMPA receptor regulatory proteins (TARPs) and discusses its role in synaptic plasticity.

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