scholarly journals A new mouse line with reduced GluA2 Q/R site RNA editing exhibits loss of dendritic spines, hippocampal CA1-neuron loss, learning and memory impairments and NMDA receptor-independent seizure vulnerability

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Lyndsey M. Konen ◽  
Amanda L. Wright ◽  
Gordon A. Royle ◽  
Gary P. Morris ◽  
Benjamin K. Lau ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Learning And Memory ◽  
Rna Editing ◽  
Dendritic Spines ◽  
Mouse Line ◽  
Neuron Loss ◽  
Memory Impairments ◽  
Hippocampal Ca1

scholarly journals Cordycepin Ameliorates Synaptic Dysfunction and Dendrite Morphology Damage of Hippocampal CA1 via A1R in Cerebral Ischemia

2021 ◽  
Vol 15 ◽  
Author(s):  
Zhao-Hui Chen ◽  
Yuan-Yuan Han ◽  
Ying-Jie Shang ◽  
Si-Yi Zhuang ◽  
Jun-Ni Huang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Synaptic Transmission ◽  
Learning And Memory ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Dendritic Morphology ◽  
Synaptic Dysfunction ◽  
Dendrite Morphology ◽  
Memory Impairments ◽  
Hippocampal Ca1

Cordycepin exerted significant neuroprotective effects and protected against cerebral ischemic damage. Learning and memory impairments after cerebral ischemia are common. Cordycepin has been proved to improve memory impairments induced by cerebral ischemia, but its underlying mechanism has not been revealed yet. The plasticity of synaptic structure and function is considered to be one of the neural mechanisms of learning and memory. Therefore, we investigated how cordycepin benefits dendritic morphology and synaptic transmission after cerebral ischemia and traced the related molecular mechanisms. The effects of cordycepin on the protection against ischemia were studied by using global cerebral ischemia (GCI) and oxygen-glucose deprivation (OGD) models. Behavioral long-term potentiation (LTP) and synaptic transmission were observed with electrophysiological recordings. The dendritic morphology and histological assessment were assessed by Golgi staining and hematoxylin-eosin (HE) staining, respectively. Adenosine A1 receptors (A1R) and adenosine A2A receptors (A2AR) were evaluated with western blotting. The results showed that cordycepin reduced the GCI-induced dendritic morphology scathing and behavioral LTP impairment in the hippocampal CA1 area, improved the learning and memory abilities, and up-regulated the level of A1R but not A2AR. In the in vitro experiments, cordycepin pre-perfusion could alleviate the hippocampal slices injury and synaptic transmission cripple induced by OGD, accompanied by increased adenosine content. In addition, the protective effect of cordycepin on OGD-induced synaptic transmission damage was eliminated by using an A1R antagonist instead of A2AR. These findings revealed that cordycepin alleviated synaptic dysfunction and dendritic injury in ischemic models by modulating A1R, which provides new insights into the pharmacological mechanisms of cordycepin for ameliorating cognitive impairment induced by cerebral ischemia.

scholarly journals Targeted Reducing of Tauopathy Alleviates Epileptic Seizures and Spatial Memory Impairment in an Optogenetically Inducible Mouse Model of Epilepsy

2021 ◽  
Vol 8 ◽  
Author(s):  
Yang Gao ◽  
Jie Zheng ◽  
Tao Jiang ◽  
Guilin Pi ◽  
Fei Sun ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Epileptic Seizures ◽  
Neuronal Firing ◽  
Spatial Learning And Memory ◽  
Memory Impairments ◽  
Optogenetic Stimulation ◽  
Hippocampal Ca1 ◽  
The Brain

Intracellular deposition of hyperphosphorylated tau has been reported in the brain of epilepsy patients, but its contribution to epileptic seizures and the association with spatial cognitive functions remain unclear. Here, we found that repeated optogenetic stimulation of the excitatory neurons in ventral hippocampal CA1 subset could induce a controllable epileptic seizure in mice. Simultaneously, the mice showed spatial learning and memory deficits with a prominently elevated total tau and phospho-tau levels in the brain. Importantly, selective facilitating tau degradation by using a novel designed proteolysis-targeting chimera named C4 could effectively ameliorate the epileptic seizures with remarkable restoration of neuronal firing activities and improvement of spatial learning and memory functions. These results confirm that abnormal tau accumulation plays a pivotal role in the epileptic seizures and the epilepsy-associated spatial memory impairments, which provides new molecular target for the therapeutics.

scholarly journals Molecular Mechanisms of Non-ionotropic NMDA Receptor Signaling

2020 ◽  
Author(s):  
Ivar S. Stein ◽  
Deborah K. Park ◽  
Jennifer N. Jahncke ◽  
Juan C. Flores ◽  
Karen Zito
Keyword(s):  
Nmda Receptor ◽  
Conformational Changes ◽  
Dendritic Spines ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Ca1 Neurons ◽  
Ion Flow ◽  
Two Photon ◽  
Large Step ◽  
Hippocampal Ca1

AbstractStructural plasticity of dendritic spines is a key component of the refinement of synaptic connections during learning. Recent studies highlight a novel role for the NMDA receptor (NMDAR), independent of ion flow, in driving spine shrinkage and LTD. Yet little is known about the molecular mechanisms that link conformational changes in the NMDAR to changes in spine size and synaptic strength. Here, using two-photon glutamate uncaging to induce plasticity in hippocampal CA1 neurons from mice and rats, we demonstrate that p38 MAPK is required downstream of conformational NMDAR signaling to drive both spine shrinkage and LTD at individual dendritic spines. In a series of pharmacological and molecular genetic experiments, we identify key components of the non-ionotropic NMDAR signaling pathway driving dendritic spine shrinkage, including the interaction between NOS1AP and nNOS, nNOS enzymatic activity, activation of MK2 and cofilin, and signaling through CaMKII. Our results represent a large step forward in delineating the molecular mechanisms of non-ionotropic NMDAR signaling that drive the shrinkage and elimination of dendritic spines during synaptic plasticity.

scholarly journals Low-Frequency Stimulation Prevents Kindling-Induced Impairment through the Activation of the Endocannabinoid System

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Sina Khajei ◽  
Khadijeh Esmaeilpour ◽  
Javad Mirnajafi-Zadeh ◽  
Vahid Sheibani ◽  
Soheila Rezakhani ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Low Frequency ◽  
Endocannabinoid System ◽  
The Novel ◽  
Memory Impairments ◽  
Low Frequency Stimulation ◽  
Hippocampal Ca1 ◽  
Significant Difference ◽  
Frequency Stimulation ◽  
Ca1 Area

Background. Cannabinoid system affects memory and has anticonvulsant effects in epileptic models. In the current study, the role of cannabinoid 1 (CB1) receptors was investigated in amelioration of the effects of low-frequency stimulation (LFS) on learning and memory impairments in kindled rats. Methods. Electrical stimulation of the hippocampal CA1 area was employed to kindle the animals. LFS was applied to the CA1 area in four trials following the last kindling stimulation. One group of animals received intraperitoneal injection of AM251 (0.1 μg/rat), a CB1 receptor antagonist, before the LFS application. Similarly, CB1 agonist WIN55-212-2 (WIN) was administrated to another group prior to LFS. The Morris water maze (MWM) and the novel object recognition (NOR) tests were executed 48 h after the last kindling stimulation to assess learning and memory. Results. Applying LFS in the kindled+LFS group restored learning and memory impairments in the kindled rats. There was a significant difference between the kindled and the kindled+LFS groups in learning and memory. The application of AM251 reduced the LFS effects significantly. Adversely, WIN acted similarly to LFS and alleviated learning and memory deficits in the kindled+WIN group. In addition, WIN did not counteract the LFS enhancing effects in the KLFS+WIN group. Conclusions. Improving effects of LFS on learning and memory impairments are mediated through the activation of the endocannabinoid (ECB) system.

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