scholarly journals Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway

PLoS Biology ◽  
2017 ◽  
Vol 15 (7) ◽  
pp. e2001246 ◽  
Author(s):  
Eunchai Kang ◽  
Danye Jiang ◽  
Yun Kyoung Ryu ◽  
Sanghee Lim ◽  
Minhye Kwak ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Hippocampal Neurons ◽  
Mtor Pathway ◽  
Postnatal Exposure

scholarly journals Post-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in mice

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xin-Ming Luo ◽  
Jing Zhao ◽  
Wen-Yue Wu ◽  
Jie Fu ◽  
Zheng-Yu Li ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Cognitive Function ◽  
Cognitive Deficits ◽  
Tyrosine Kinases ◽  
Hippocampal Neurons ◽  
Water Maze ◽  
Behavioral Tests ◽  
Life Threatening ◽  
The Brain ◽  
Normal Object

Abstract Background Status epilepticus (SE) is a life-threatening neurological disorder. The hippocampus, as an important area of the brain that regulates cognitive function, is usually damaged after SE, and cognitive deficits often result from hippocampal neurons lost after SE. Fyn, a non-receptor Src family of tyrosine kinases, is potentially associated with the onset of seizure. Saracatinib, a Fyn inhibitor, suppresses epileptogenesis and reduces epileptiform spikes. However, whether saracatinib inhibits cognitive deficits after SE is still unknown. Methods In the present study, a pilocarpine-induced SE mouse model was used to answer this question by using the Morris water maze and normal object recognition behavioral tests. Results We found that saracatinib inhibited the loss in cognitive function following SE. Furthermore, we found that the number of hippocampal neurons in the saracatinib treatment group was increased, when compared to the SE group. Conclusions These results showed that saracatinib can improve cognitive functions by reducing the loss of hippocampal neurons after SE, suggesting that Fyn dysfunction is involved in cognitive deficits after SE, and that the inhibition of Fyn is a possible treatment to improve cognitive function in SE patients.

scholarly journals Hyperactive mTOR signals in the proopiomelanocortin-expressing hippocampal neurons cause age-dependent epilepsy and premature death in mice

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yuki Matsushita ◽  
Yasunari Sakai ◽  
Mitsunori Shimmura ◽  
Hiroshi Shigeto ◽  
Miki Nishio ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Focal Cortical Dysplasia ◽  
Mossy Fibers ◽  
Premature Death ◽  
Mtor Pathway ◽  
Conditional Knockout ◽  
Inhibitory Neurons ◽  
Sequencing Data ◽  
Functional Roles ◽  
Synaptic Markers

Abstract Epilepsy is a frequent comorbidity in patients with focal cortical dysplasia (FCD). Recent studies utilizing massive sequencing data identified subsets of genes that are associated with epilepsy and FCD. AKT and mTOR-related signals have been recently implicated in the pathogenic processes of epilepsy and FCD. To clarify the functional roles of the AKT-mTOR pathway in the hippocampal neurons, we generated conditional knockout mice harboring the deletion of Pten (Pten-cKO) in Proopiomelanocortin-expressing neurons. The Pten-cKO mice developed normally until 8 weeks of age, then presented generalized seizures at 8–10 weeks of age. Video-monitored electroencephalograms detected paroxysmal discharges emerging from the cerebral cortex and hippocampus. These mice showed progressive hypertrophy of the dentate gyrus (DG) with increased expressions of excitatory synaptic markers (Psd95, Shank3 and Homer). In contrast, the expression of inhibitory neurons (Gad67) was decreased at 6–8 weeks of age. Immunofluorescence studies revealed the abnormal sprouting of mossy fibers in the DG of the Pten-cKO mice prior to the onset of seizures. The treatment of these mice with an mTOR inhibitor rapamycin successfully prevented the development of seizures and reversed these molecular phenotypes. These data indicate that the mTOR pathway regulates hippocampal excitability in the postnatal brain.

P.1.002 Cognitive deficits due to chronic consumption of Δ9-tetrahydrocannabinol during adolescence: role of 5-HT6-mTOR pathway

2016 ◽  
Vol 26 ◽  
pp. S3-S4 ◽  
Author(s):  
C. Berthoux ◽  
A.M. Hamieh ◽  
J. Bockaert ◽  
P. Marin ◽  
C. Bécamel
Keyword(s):  
Cognitive Deficits ◽  
Mtor Pathway

scholarly journals Interleukin-1 receptor on hippocampal neurons drives social withdrawal and cognitive deficits after chronic social stress

2020 ◽  
Author(s):  
Damon J. DiSabato ◽  
Daniel P. Nemeth ◽  
Xiaoyu Liu ◽  
Kristina G. Witcher ◽  
Shane M. O’Neil ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Social Stress ◽  
Hippocampal Neurons ◽  
Social Withdrawal ◽  
Interleukin 1 ◽  
Chronic Social Stress

scholarly journals Exercise training improves motor skill learning via selective activation of mTOR

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw1888 ◽  
Author(s):  
Kai Chen ◽  
Yuhan Zheng ◽  
Ji-an Wei ◽  
Huan Ouyang ◽  
Xiaodan Huang ◽  
...  
Keyword(s):  
Exercise Training ◽  
Motor Learning ◽  
Cognitive Deficits ◽  
Molecular Mechanisms ◽  
Pyramidal Neurons ◽  
Ex Vivo ◽  
Mtor Pathway ◽  
Skill Learning ◽  
Mechanistic Target Of Rapamycin

Physical exercise improves learning and memory, but little in vivo evidence has been provided to illustrate the molecular mechanisms. Here, we show that chronic treadmill exercise activates the mechanistic target of rapamycin (mTOR) pathway in mouse motor cortex. Both ex vivo and in vivo recordings suggest that mTOR activation leads to potentiated postsynaptic excitation and enhanced neuronal activity of layer 5 pyramidal neurons after exercise, in association with increased oligodendrogenesis and axonal myelination. Exercise training also increases dendritic spine formation and motor learning. Together, exercise activates mTOR pathway, which is necessary for spinogenesis, neuronal activation, and axonal myelination leading to improved motor learning. This model provides new insights for neural network adaptations through exercises and supports the intervention of cognitive deficits using exercise training.

Long noncoding RNA Nespas inhibits apoptosis of epileptiform hippocampal neurons by inhibiting the PI3K/Akt/mTOR pathway

2021 ◽  
Vol 398 (1) ◽  
pp. 112384
Author(s):  
Hongxuan Feng ◽  
Qian Gui ◽  
Guanhui Wu ◽  
Wei Zhu ◽  
Xiaofeng Dong ◽  
...  
Keyword(s):  
Long Noncoding Rna ◽  
Hippocampal Neurons ◽  
Noncoding Rna ◽  
Mtor Pathway

scholarly journals Amyloid-β effects on synapses and memory require AMPA receptor subunit GluA3

2016 ◽  
Vol 113 (42) ◽  
pp. E6526-E6534 ◽  
Author(s):  
Niels R. Reinders ◽  
Yvonne Pao ◽  
Maria C. Renner ◽  
Carla M. da Silva-Matos ◽  
Tessa R. Lodder ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Cognitive Deficits ◽  
Hippocampal Neurons ◽  
Memory Impairment ◽  
Amyloid Β ◽  
Memory Formation ◽  
Aβ Oligomers ◽  
Ampa Receptor Subunit ◽  
Early Phases

Amyloid-β (Aβ) is a prime suspect for causing cognitive deficits during the early phases of Alzheimer’s disease (AD). Experiments in AD mouse models have shown that soluble oligomeric clusters of Aβ degrade synapses and impair memory formation. We show that all Aβ-driven effects measured in these mice depend on AMPA receptor (AMPAR) subunit GluA3. Hippocampal neurons that lack GluA3 were resistant against Aβ-mediated synaptic depression and spine loss. In addition, Aβ oligomers blocked long-term synaptic potentiation only in neurons that expressed GluA3. Furthermore, although Aβ-overproducing mice showed significant memory impairment, memories in GluA3-deficient congenics remained unaffected. These experiments indicate that the presence of GluA3-containing AMPARs is critical for Aβ-mediated synaptic and cognitive deficits.

Glyphosate exposure induces synaptic impairment in hippocampal neurons and cognitive deficits in developing rats

2021 ◽  
Author(s):  
Sebastian Luna ◽  
Lorena P. Neila ◽  
Rodrigo Vena ◽  
Conrado Borgatello ◽  
Silvana B. Rosso
Keyword(s):  
Cognitive Deficits ◽  
Hippocampal Neurons

scholarly journals Cirbp-PSD95 axis protects against hypobaric hypoxia-induced aberrant morphology of hippocampal dendritic spines and cognitive deficits

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yang Zhou ◽  
Huanyu Lu ◽  
Ying Liu ◽  
Zaihua Zhao ◽  
Qian Zhang ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Dendritic Spine ◽  
Hippocampal Neurons ◽  
Hypobaric Hypoxia ◽  
Rna Binding ◽  
Spine Injury ◽  
Spine Density ◽  
Hypoxia Exposure ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region

AbstractHypobaric hypoxia (HH) is a typical characteristic of high altitude environment and causes a spectrum of pathophysiological effects, including headaches, gliovascular dysfunction and cognitive retardation. Here, we sought to understand the mechanisms underlying cognitive deficits under HH exposure. Our results showed that hypobaric hypoxia exposure impaired cognitive function and suppressed dendritic spine density accompanied with increased neck length in both basal and apical hippocampal CA1 region neurons in mice. The expression of PSD95, a vital synaptic scaffolding molecule, is down-regulated by hypobaric hypoxia exposure and post-transcriptionally regulated by cold-inducible RNA-binding protein (Cirbp) through 3′-UTR region binding. PSD95 expressing alleviates hypoxia-induced dendritic spine morphology changes of hippocampal neurons and memory deterioration. Moreover, overexpressed Cirbp in hippocampus rescues HH-induced abnormal expression of PSD95 and attenuates hypoxia-induced dendritic spine injury and cognitive retardation. Thus, our findings reveal a novel mechanism that Cirbp-PSD-95 axis appears to play an essential role in HH-induced cognitive dysfunction in mice.

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