scholarly journals Cognitive impairment in a classical rat model of chronic migraine may be due to alterations in hippocampal synaptic plasticity and N-methyl-D-aspartate receptor subunits

2020 ◽  
Vol 16 ◽  
pp. 174480692095958
Author(s):  
Mingjie Zhang ◽  
Yufei Liu ◽  
Guanqun Hu ◽  
Li Kang ◽  
Ye Ran ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Spatial Cognition ◽  
Long Term Potentiation ◽  
Therapeutic Effects ◽  
Hippocampal Synaptic Plasticity ◽  
Aspartate Receptor ◽  
Term Potentiation ◽  
Inflammatory Soup

Although migraine is a major global public health problem, its impact on cognitive abilities remains controversial. Thus, the present study investigated the effects of repeated administration of inflammatory soup to the dura of rats, over three weeks, on spatial cognition, hippocampal synaptic plasticity, and the expression of N-methyl-D-aspartate receptor subunits. Additionally, low doses of amitriptyline (5 mg/kg) were applied to assess its therapeutic effects. The inflammatory soup group exhibited significant reductions in the cutaneous stimulation threshold, presence of mild cognitive impairment, and decreased long-term potentiation in right hippocampus. However, amitriptyline improved pain behaviors, enhanced cognitive function, and increased synaptic plasticity in the inflammatory soup rats. On the other hand, the administration of amitriptyline to normal rats negatively influenced synaptic plasticity and reduced the expression of N-methyl-D-aspartate receptor subunits. The present results indicate that inflammatory soup-induced dural nociception led to impairments in spatial cognition that could be attributed to reductions in hippocampal long-term potentiation and the decreased expression of N-methyl-D-aspartate receptor subunits.

scholarly journals rTMS Ameliorates Prenatal Stress–Induced Cognitive Deficits in Male-Offspring Rats Associated With BDNF/TrkB Signaling Pathway

2019 ◽  
Vol 33 (4) ◽  
pp. 271-283 ◽  
Author(s):  
Yingchun Shang ◽  
Xin Wang ◽  
Fangjuan Li ◽  
Tao Yin ◽  
Jianhai Zhang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Cognition ◽  
Cognitive Deficits ◽  
Prenatal Stress ◽  
Long Term Potentiation ◽  
Signaling Proteins ◽  
Ca1 Region ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation

Background. Growing evidences suggest that brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) plays a key role in the regulation of hippocampal synaptic plasticity in a prenatal stress (PNS) rat model. Repetitive transcranial magnetic stimulation (rTMS) is currently being acknowledged to affect attention and memory in both preclinical and clinical studies, although the mechanism is still unclear. Objective. The current study aimed to explore whether a whole brain rTMS (5 Hz, 14 days) could ameliorate cognitive dysfunction–induced PNS in male offspring, and examine if the positive effect of rTMS was associated with the BDNF/TrkB signaling in the hippocampus. Methods. The rats were randomly divided into 5 groups: CON, PNS, PNS + rTMS, PNS + rTMS + DMSO (dimethyl sulfoxide), and PNS + rTMS + K252a. Spatial cognition was evaluated by using Morris water maze test. Following behavioral assessment, both paired-pulse facilitation and long-term potentiation were recorded from Schaffer collaterals to CA1 region in the hippocampus. Synaptic, apoptotic, and BDNF/TrkB signaling proteins were measured by Western blot. Results. PNS-exposed offspring exhibited cognitive deficits, long-term potentiation inhibition in the hippocampus, the decrease of synaptic and BDNF/TrkB signaling proteins expression, apoptosis, and reduced number of cells in the CA1 region. Five-hertz rTMS significantly alleviated the PNS-induced abnormalities. However, the effect of rTMS was antagonized by intracerebroventricular infusion of K252a (a TrkB inhibitor). Conclusions. The findings suggest that 5-Hz rTMS significantly improves the impairment of spatial cognition and hippocampal synaptic plasticity, which is possibly associated with the activation of BDNF/TrkB signaling.

scholarly journals (2S,6S)- and (2R,6R)-hydroxynorketamine inhibit the induction of NMDA receptor-dependent LTP at hippocampal CA1 synapses in mice

2020 ◽  
Vol 4 ◽  
pp. 239821282095784
Author(s):  
Heather Kang ◽  
Pojeong Park ◽  
Muchun Han ◽  
Patrick Tidball ◽  
John Georgiou ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Long Term Potentiation ◽  
Aspartate Receptor ◽  
Term Potentiation ◽  
Hippocampal Ca1 ◽  
Mouse Hippocampus ◽  
Site Of Action ◽  
A Site

The ketamine metabolite (2 R,6 R)-hydroxynorketamine has been proposed to have rapid and persistent antidepressant actions in rodents, but its mechanism of action is controversial. We have compared the ability of ( R,S)-ketamine with the (2 S,6 S)- and (2 R,6 R)-isomers of hydroxynorketamine to affect the induction of N-methyl-d-aspartate receptor–dependent long-term potentiation in the mouse hippocampus. Following pre-incubation of these compounds, we observed a concentration-dependent (1–10 μM) inhibition of long-term potentiation by ketamine and a similar effect of (2 S,6 S)-hydroxynorketamine. At a concentration of 10 μM, (2 R,6 R)-hydroxynorketamine also inhibited the induction of long-term potentiation. These findings raise the possibility that inhibition of N-methyl-d-aspartate receptor–mediated synaptic plasticity is a site of action of the hydroxynorketamine metabolites with respect to their rapid and long-lasting antidepressant-like effects.

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 Persistent memories of long-term potentiation and the N-methyl-d-aspartate receptor

2019 ◽  
Vol 3 ◽  
pp. 239821281984821 ◽  
Author(s):  
TVP Bliss ◽  
GL Collingridge
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Brain Disorders ◽  
Molecular Pharmacology ◽  
Cellular Mechanisms ◽  
Long Term Depression ◽  
Aspartate Receptor ◽  
Term Potentiation ◽  
Core Feature

In this article, we describe our involvement in the early days of research into long-term potentiation. We start with a description of the early experiments conducted in Oslo and London where long-term potentiation was first characterised. We discuss the ways in which the molecular pharmacology of glutamate receptors control the induction and expression of long-term potentiation and its counterpart, long-term depression. We then go on to summarise the extraordinary advances in understanding the cellular mechanisms of synaptic plasticity that have taken place in the subsequent half century. Finally, the increasing evidence that impaired long-term potentiation is a core feature of many brain disorders (LToPathies) is addressed by way of a few selected examples.

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.

Hippocampal synaptic plasticity in neurodegenerative diseases: Aß, tau and beyond

Neuroforum ◽  
2018 ◽  
Vol 24 (3) ◽  
pp. A133-A141
Author(s):  
Detlef Balschun ◽  
Michael J. Rowan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Hippocampal Synaptic Plasticity ◽  
Term Potentiation ◽  
Neurological Illnesses ◽  
Early Alzheimer’S Disease ◽  
Opposing Effects

Abstract The study of long-term potentiation (LTP) and long-term depression (LTD) in disease models provides essential mechanistic insight into synaptic dysfunction and remodelling in many neuropsychiatric and neurological illnesses. The ability of misfolded forms of the two key proteins of Alzheimer’s disease, amyloid ß (Aß) and the microtubule binding tau to disrupt hippocampal synaptic plasticity, engender highly sensitive litmus tests of impending synaptic failure and subsequent structural pathology. Many transgenic and injection-induced rodent models show rapid and persistent inhibition of LTP, and sometimes opposing effects of Aß and tau on LTD. Intriguingly, both intracellular and extracellular actions of these proteins are implicated. Both directly targeting these proteins and abrogating their synaptotoxic actions are being explored to redress the insidious shift from physiological to pathological plasticity in early Alzheimer’s disease.

scholarly journals NMDA receptor-dependent long-term potentiation comprises a family of temporally overlapping forms of synaptic plasticity that are induced by different patterns of stimulation

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130131 ◽  
Author(s):  
Pojeong Park ◽  
Arturas Volianskis ◽  
Thomas M. Sanderson ◽  
Zuner A. Bortolotto ◽  
David E. Jane ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Recent Work ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Extensive Literature ◽  
Synaptic Activation ◽  
Aspartate Receptor ◽  
Term Potentiation

N -methyl- d -aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) is extensively studied since it is believed to use the same molecular mechanisms that are required for many forms of learning and memory. Unfortunately, many controversies exist, not least the seemingly simple issue concerning the locus of expression of LTP. Here, we review our recent work and some of the extensive literature on this topic and present new data that collectively suggest that LTP can be explained, during its first few hours, by the coexistence of at least three mechanistically distinct processes that are all triggered by the synaptic activation of NMDARs.

scholarly journals Neuraminidase Inhibition Primes Short-Term Depression and Suppresses Long-Term Potentiation of Synaptic Transmission in the Rat Hippocampus

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Alina Savotchenko ◽  
Arthur Romanov ◽  
Dmytro Isaev ◽  
Oleksandr Maximyuk ◽  
Vadym Sydorenko ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Science Studies ◽  
Hippocampal Slices ◽  
Control Level ◽  
Specific Inhibitor ◽  
Long Term Potentiation ◽  
Short Term ◽  
Term Potentiation

Neuraminidase (NEU) is a key enzyme that cleaves negatively charged sialic acid residues from membrane proteins and lipids. Clinical and basic science studies have shown that an imbalance in NEU metabolism or changes in NEU activity due to various pathological conditions parallel with behavior and cognitive impairment. It has been suggested that the decreases of NEU activity could cause serious neurological consequences. However, there is a lack of direct evidences that modulation of endogenous NEU activity can impair neuronal function. Using combined rat entorhinal cortex/hippocampal slices and a specific inhibitor of NEU, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (NADNA), we examined the effect of downregulation of NEU activity on different forms of synaptic plasticity in the hippocampal CA3-to-CA1 network. We show that NEU inhibition results in a significant decrease in long-term potentiation (LTP) and an increase in short-term depression. Synaptic depotentiation restores LTP in NADNA-pretreated slices to the control level. These data suggest that short-term NEU inhibition produces the LTP-like effect on neuronal network, which results in damping of further LTP induction. Our findings demonstrate that downregulation of NEU activity could have a major impact on synaptic plasticity and provide a new insight into the cellular mechanism underlying behavioral and cognitive impairment associated with abnormal metabolism of NEU.

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.

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