scholarly journals Targeting CDK5 post-stroke provides long-term neuroprotection and rescues synaptic plasticity

2016 ◽  
Vol 37 (6) ◽  
pp. 2208-2223 ◽  
Author(s):  
Johanna A Gutiérrez-Vargas ◽  
Herman Moreno ◽  
Gloria P Cardona-Gómez
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Neurotrophic Factor ◽  
Neuronal Loss ◽  
Long Term Potentiation ◽  
Brain Derived Neurotrophic Factor ◽  
Cyclin Dependent Kinase ◽  
Post Stroke ◽  
Cyclin Dependent Kinase 5

Post-stroke cognitive impairment is a major cause of long-term neurological disability. The prevalence of post-stroke cognitive deficits varies between 20% and 80% depending on brain region, country, and diagnostic criteria. The biochemical mechanisms underlying post-stroke cognitive impairment are not known in detail. Cyclin-dependent kinase 5 is involved in neurodegeneration, and its dysregulation contributes to cognitive disorders and dementia. Here, we administered cyclin-dependent kinase 5-targeting gene therapy to the right hippocampus of ischemic rats after transient right middle cerebral artery occlusion. Cyclin-dependent kinase 5 RNA interference prevented the impairment of reversal learning four months after ischemia as well as neuronal loss, tauopathy, and microglial hyperreactivity. Additionally, cyclin-dependent kinase 5 silencing increased the expression of brain-derived neurotrophic factor in the hippocampus. Furthermore, deficits in hippocampal long-term potentiation produced by excitotoxic stimulation were rescued by pharmacological blockade of cyclin-dependent kinase 5. This recovery was blocked by inhibition of the TRKB receptor. In summary, these findings demonstrate the beneficial impact of cyclin-dependent kinase 5 reduction in preventing long-term post-ischemic neurodegeneration and cognitive impairment as well as the role of brain-derived neurotrophic factor/TRKB in the maintenance of normal synaptic plasticity.

scholarly journals The Association of Brain-Derived Neurotrophic Factor with Long-Term Potentiation

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Zahra Salimi ◽  
Farshad Moradpour ◽  
Zahra Rashidi ◽  
Fatemeh Zarei ◽  
Mohammad Rasool Khazaei ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Neurotrophic Factor ◽  
Synapse Formation ◽  
Long Term Potentiation ◽  
Brain Derived Neurotrophic Factor ◽  
Synaptic Efficacy ◽  
Term Potentiation ◽  
The Central Nervous System

: Long-term potentiation (LTP) is one of the most important topics in neuroscience. It refers to a long-lasting increase in synaptic efficacy and is considered as a molecular and cellular mechanism of learning and memory. Neurotrophins play essential roles in different processes in the central nervous system (CNS), such as synaptogenesis, survival of specific populations of neurons, and neuroplasticity. Some evidence suggests that neurotrophins also participate in the synaptic plasticity related to learning and memory formation. Brain-derived neurotrophic factor (BDNF) is an important neurotrophic factor that is extensively expressed in the hippocampus and cerebral cortex, where it promotes neuroprotection, increases synaptogenesis and neurotransmission, and mediates synapse formation and synaptic plasticity. In this review, we first focused on the research investigating the effects of BDNF on synaptic plasticity and LTP induction and then reviewed the neuronal signaling molecules employed by BDNF to promote its effects on these processes.

scholarly journals Mechanisms of high-intensity sound exposure on inhibiting hippocampal long-term potentiation: role of brain-derived neurotrophic factor

2019 ◽  
Author(s):  
Júnia L. de Deus ◽  
Mateus R. Amorim ◽  
Aline B. Ribeiro ◽  
Procópio C. G. Barcellos-Filho ◽  
César C. Ceballos ◽  
...  
Keyword(s):  
Emotional Disorders ◽  
Neurotrophic Factor ◽  
High Intensity ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Brain Derived Neurotrophic Factor ◽  
Sound Stimulation ◽  
Sound Exposure ◽  
Term Potentiation

AbstractExposure to humans and experimental animals to loud noises produce cognitive and emotional disorders and recent studies have shown that hippocampal neuronal function is affected by auditory stimulation or deprivation. We have found previously that in the hippocampus of rats exposed to high-intensity sound (110 dB) for one-minute the Schaffer-CA1 long-term potentiation (LTP) is strongly inhibited. Here we investigated possible mechanisms involved in this effect. We found, using c-fos expression, that exposure to 110 dB sound-activated neurons in the CA1 and CA3 hippocampal region. Using electrophysiological recordings in hippocampal slices, we found that both GABAergic and glutamatergic neurotransmission were unaffected by high-intensity sound stimulation. However, hippocampal brain-derived neurotrophic factor (BDNF), which is involved in promoting hippocampal synaptic plasticity, presented decreased levels in sound-stimulated animals. Perfusion of slices with BDNF revert the inhibition of LTP after a single sound stimulus in comparison to sham-stimulated rats. Furthermore, the perfusion with LM 22A4, a TrkB receptor agonist also rescued LTP from sound-stimulated animals. Our results strongly suggest that the exposure to high-intensity sound inhibits the BDNF production in the hippocampus, which could be a possible mechanism of the inhibition of LTP by high-intensity sound exposure.

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