scholarly journals Involvement of p38 MAPK in Synaptic Function and Dysfunction

2020 ◽  
Vol 21 (16) ◽  
pp. 5624 ◽  
Author(s):  
Chiara Falcicchia ◽  
Francesca Tozzi ◽  
Ottavio Arancio ◽  
Daniel Martin Watterson ◽  
Nicola Origlia
Keyword(s):  
P38 Mapk ◽  
Neuronal Plasticity ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Synaptic Efficacy ◽  
Term Potentiation ◽  
Responsive Element

Many studies have revealed a central role of p38 MAPK in neuronal plasticity and the regulation of long-term changes in synaptic efficacy, such as long-term potentiation (LTP) and long-term depression (LTD). However, p38 MAPK is classically known as a responsive element to stress stimuli, including neuroinflammation. Specific to the pathophysiology of Alzheimer’s disease (AD), several studies have shown that the p38 MAPK cascade is activated either in response to the Aβ peptide or in the presence of tauopathies. Here, we describe the role of p38 MAPK in the regulation of synaptic plasticity and its implication in an animal model of neurodegeneration. In particular, recent evidence suggests the p38 MAPK α isoform as a potential neurotherapeutic target, and specific inhibitors have been developed and have proven to be effective in ameliorating synaptic and memory deficits in AD mouse models.

scholarly journals Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing

2021 ◽  
Author(s):  
Sujeong Yang ◽  
Sylvain Gigout ◽  
Angelo Molinaro ◽  
Yuko Naito-Matsui ◽  
Sam Hilton ◽  
...  
Keyword(s):  
Chondroitin Sulphate ◽  
Memory Loss ◽  
Memory Deficits ◽  
Long Term Potentiation ◽  
Aged Mice ◽  
Age Related ◽  
Term Potentiation ◽  
Early Memory

AbstractPerineuronal nets (PNNs) are chondroitin sulphate proteoglycan-containing structures on the neuronal surface that have been implicated in the control of neuroplasticity and memory. Age-related reduction of chondroitin 6-sulphates (C6S) leads to PNNs becoming more inhibitory. Here, we investigated whether manipulation of the chondroitin sulphate (CS) composition of the PNNs could restore neuroplasticity and alleviate memory deficits in aged mice. We first confirmed that aged mice (20-months) showed memory and plasticity deficits. They were able to retain or regain their cognitive ability when CSs were digested or PNNs were attenuated. We then explored the role of C6S in memory and neuroplasticity. Transgenic deletion of chondroitin 6-sulfotransferase (chst3) led to a reduction of permissive C6S, simulating aged brains. These animals showed very early memory loss at 11 weeks old. Importantly, restoring C6S levels in aged animals rescued the memory deficits and restored cortical long-term potentiation, suggesting a strategy to improve age-related memory impairment.

scholarly journals Staufen1 Regulation of Protein Synthesis-Dependent Long-Term Potentiation and Synaptic Function in Hippocampal Pyramidal Cells

2008 ◽  
Vol 28 (9) ◽  
pp. 2896-2907 ◽  
Author(s):  
Geneviève Lebeau ◽  
Marjolaine Maher-Laporte ◽  
Lisa Topolnik ◽  
Charles E. Laurent ◽  
Wayne Sossin ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Translational Control ◽  
Rna Binding ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Down Regulation ◽  
Spine Shape ◽  
Term Potentiation

ABSTRACT Staufen1 (Stau1) is an RNA-binding protein involved in transport, localization, decay, and translational control of mRNA. In neurons, it is present in cell bodies and also in RNA granules which are transported along dendrites. Dendritic mRNA localization might be involved in long-term synaptic plasticity and memory. To determine the role of Stau1 in synaptic function, we examined the effects of Stau1 down-regulation in hippocampal slice cultures using small interfering RNA (siRNA). Biolistic transfection of Stau1 siRNA resulted in selective down-regulation of Stau1 in slice cultures. Consistent with a role of Stau1 in transporting mRNAs required for synaptic plasticity, Stau1 down-regulation impaired the late form of chemically induced long-term potentiation (L-LTP) without affecting early-LTP, mGluR1/5-mediated long-term depression, or basal evoked synaptic transmission. Stau1 down-regulation decreased the amplitude and frequency of miniature excitatory postsynaptic currents, suggesting a role in maintaining efficacy at hippocampal synapses. At the cellular level, Stau1 down-regulation shifted spine shape from regular to elongated spines, without changes in spine density. The change in spine shape could be rescued by an RNA interference-resistant Stau1 isoform. Therefore, Stau1 is important for processing and/or transporting in dendrites mRNAs that are critical in regulation of synaptic strength and maintenance of functional connectivity changes underlying hippocampus-dependent learning and memory.

Neurotrophins and Proneurotrophins: Focus on Synaptic Activity and Plasticity in the Brain

2017 ◽  
Vol 23 (6) ◽  
pp. 587-604 ◽  
Author(s):  
Julien Gibon ◽  
Philip A. Barker
Keyword(s):  
Long Term Potentiation ◽  
Synaptic Activity ◽  
Cellular Processes ◽  
Term Potentiation ◽  
Neurotrophin 3 ◽  
New Findings ◽  
The Central Nervous System ◽  
The Brain

Neurotrophins have been intensively studied and have multiple roles in the brain. Neurotrophins are first synthetized as proneurotrophins and then cleaved intracellularly and extracellularly. Increasing evidences demonstrate that proneurotrophins and mature neurotrophins exerts opposing role in the central nervous system. In the present review, we explore the role of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4) and their respective proform in cellular processes related to learning and memory. We focused on their roles in synaptic activity and plasticity in the brain with an emphasis on long-term potentiation, long-term depression, and basal synaptic transmission in the hippocampus and the temporal lobe area. We also discuss new findings on the role of the Val66Met polymorphism on the BDNF propeptide on synaptic activity.

scholarly journals Examination of the role of cGMP in long-term potentiation in the CA1 region of the hippocampus.

1996 ◽  
Vol 3 (1) ◽  
pp. 42-48 ◽  
Author(s):  
D K Selig ◽  
M R Segal ◽  
D Liao ◽  
R C Malenka ◽  
R Malinow ◽  
...  
Keyword(s):  
Long Term Potentiation ◽  
Ca1 Region ◽  
Term Potentiation

scholarly journals GPR68 deletion impairs hippocampal long-term potentiation and passive avoidance behavior

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yuanyuan Xu ◽  
Mike T. Lin ◽  
Xiang-ming Zha
Keyword(s):  
Passive Avoidance ◽  
Pyramidal Neurons ◽  
Granule Cells ◽  
Hippocampal Slices ◽  
Synaptic Cleft ◽  
Long Term Potentiation ◽  
Synaptic Function ◽  
Metabotropic Receptor ◽  
Term Potentiation

Abstract Increased neural activities reduced pH at the synaptic cleft and interstitial spaces. Recent studies have shown that protons function as a neurotransmitter. However, it remains unclear whether protons signal through a metabotropic receptor to regulate synaptic function. Here, we showed that GPR68, a proton-sensitive GPCR, exhibited wide expression in the hippocampus, with higher expression observed in CA3 pyramidal neurons and dentate granule cells. In organotypic hippocampal slice neurons, ectopically expressed GPR68-GFP was present in dendrites, dendritic spines, and axons. Recordings in hippocampal slices isolated from GPR68−/− mice showed a reduced fiber volley at the Schaffer collateral-CA1 synapses, a reduced long-term potentiation (LTP), but unaltered paired-pulse ratio. In a step-through passive avoidance test, GPR68−/− mice exhibited reduced avoidance to the dark chamber. These findings showed that GPR68 contributes to hippocampal LTP and aversive fear memory.

scholarly journals Role of Voltage-Dependent Calcium Channel Long-Term Potentiation (LTP) and NMDA LTP in Spatial Memory

2000 ◽  
Vol 20 (24) ◽  
pp. 9272-9276 ◽  
Author(s):  
Albert M. Borroni ◽  
Harlan Fichtenholtz ◽  
Brian L. Woodside ◽  
Timothy J. Teyler
Keyword(s):  
Spatial Memory ◽  
Calcium Channel ◽  
Long Term Potentiation ◽  
Voltage Dependent Calcium Channel ◽  
Term Potentiation ◽  
Voltage Dependent

scholarly journals The Role of Extracellular Regulated Kinases I/II in Late-Phase Long-Term Potentiation

2002 ◽  
Vol 22 (13) ◽  
pp. 5432-5441 ◽  
Author(s):  
Kobi Rosenblum ◽  
Marie Futter ◽  
Karen Voss ◽  
Muriel Erent ◽  
Paul A. Skehel ◽  
...  
Keyword(s):  
Late Phase ◽  
Long Term Potentiation ◽  
Term Potentiation
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