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 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 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 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.

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.

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

2020 ◽  
Author(s):  
Xinming Luo ◽  
Jing Zhao ◽  
Wenyue Wu ◽  
Jie Fu ◽  
Zhengyu Li ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Cognitive Function ◽  
Cognitive Deficits ◽  
Tyrosine Kinases ◽  
Hippocampal Neurons ◽  
Water Maze ◽  
Behavioral Tests ◽  
Life Threatening ◽  
The Brain ◽  
Normal Object

Abstract BackgroundStatus 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.MethodsIn 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.ResultsWe 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.ConclusionsThese 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 Post-status epilepticus treatment with the Fyn inhibitor, saracatinib, improves cognitive function in mice

2020 ◽  
Author(s):  
Xinming Luo ◽  
Jing Zhao ◽  
Wenyue Wu ◽  
Jie Fu ◽  
Zhengyu Li ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Cognitive Function ◽  
Cognitive Deficits ◽  
Tyrosine Kinases ◽  
Hippocampal Neurons ◽  
Water Maze ◽  
Behavioral Tests ◽  
Life Threatening ◽  
The Brain ◽  
Normal Object

Abstract BackgroundStatus 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. MethodsIn 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. ResultsWe 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. ConclusionsThese 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 Cofilin pathology is a new player on α-synuclein-induced spine impairment in models of hippocampal synucleinopathy

2021 ◽  
Author(s):  
MI Oliveira da Silva ◽  
M Santejo ◽  
IW Babcock ◽  
A Magalhães ◽  
LS Minamide ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Deficits ◽  
Hippocampal Neurons ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Cellular Prion Protein ◽  
Actin Binding ◽  
Synaptic Dysfunction ◽  
Neuronal Dysfunction ◽  
Rod Structures

AbstractCognitive dysfunction and dementia are presently recognized as major complications in α-synucleinopathies, namely in Dementia with Lewy Bodies (DLB) and Parkinson’s disease with dementia (PDD). In these disorders, α-Synuclein (αSyn) accumulation affects severely the hippocampus by inducing synaptic dysfunction which culminates in cognitive impairment. To characterize the mechanisms underlying αSyn-induced neuronal dysfunction we analysed the effect of overexpression or extracellular administration of αSyn on hippocampal neurons. We observed that αSyn induces the dysregulation of the actin-binding protein cofilin and its assembly into rod structures in a mechanism mediated by the cellular prion protein (PrPC). Moreover, we unraveled cofilin pathology as mediator of αSyn-induced dendritic spine impairment in hippocampal neurons. Importantly, in a synucleinopathy mouse model with cognitive impairment we validated cofilin dysregulation and synaptic dysfunction at the same age when cognitive deficits were observed. Our data supports cofilin as a novel player on hippocampal synaptic dysfunction triggered by αSyn on Lewy Body dementias.

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