Mechanisms and prevention of axonal damage in response to mechanical trauma to cultured neurons

2021 ◽  
Author(s):  
Devrim Kilinc
Keyword(s):  
Axonal Damage ◽  
Mechanical Trauma ◽  
Cultured Neurons

scholarly journals The Effect of Valproic Acid on the Transcriptional Activity of Ngf and Bdnf Genes of in Vitro Cultured Neurons Under Oxidative Stress Conditions

2021 ◽  
Vol 15 ◽  
pp. 371-375
Author(s):  
A. D. Filev ◽  
E. S. Ershova ◽  
E.A. Savinova ◽  
A. M. Кalakov ◽  
N. N. Veiko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Valproic Acid ◽  
Transcriptional Activity ◽  
Mechanical Damage ◽  
Receptor Activation ◽  
Mechanical Trauma ◽  
Cultured Neurons ◽  
Genes Expression ◽  
Neuronal Processes

Brain-derived neurotrophic factor (BDNF) is a secretory molecule that promotes peripheral neurons synaptic transmission and plasticity by TrkB receptor activation. This is shown in cultured central nervous system (CNS) neurons, including hippocampal and cortical cholinergic, dopaminergic and serotonergic neurons. Hypotheses suggesting that BDNF may play a potential role in the pathophysiology of schizophrenia are based on the key role of BDNF in the synaptic plasticity and, consequently, regulation of cognitive functions. In the schizophrenia treatment valproic acid is used in complex combined therapy regimens. Treatment of schizophrenia patients with valproate increases the BDNF level. Since it is not yet clear whether the BDNF protein levels measured in serum samples and in the brain correlate, we investigated valproate effects on the cultured neurons Bdnf transcription level. The primary neuron-glia culture was obtained from the cerebellum of 8-9-day-old Wistar rats. Valproic acid was added to the neurons (at a concentration of 50 µg/ml), oxidative stress was stimulated by 40 µMof H2O2, and injury was caused by mechanical damage to the neuron culture. It was shown that valproic acid in 3-24 hours increases the transcriptional activity of the Bdnf and Ngf (nerve growth factor) genes 2–2.5-fold (p<0.01) and approximately 1.5-fold (p<0.01), respectively. Mechanical trauma, unlike oxidative stress, activates the transcriptional activity of the Ngf and Bdnf genes (p<0.01). However, under oxidative stress and mechanical damage to neurons, the effect of valproic acid on the Ngf and Bdnf genes expression was insignificant. Fluorescence microscopy analysis using specific antibodies to neurons (anti-Map-2) showed that in the presence of valproic acid, the number of neuronal processes and contacts between them significantly increased. Evidently, valproate addition to antipsychotics can be effective for the overall clinical response. Relatively little research has been done on the signaling pathways in neurons that are activated by the valproic acid. However, we have obtained evidence of activation of the Ngf and Bdnf genes transcription in cultured neurons in vitro. We also found that in the presence of valproic acid, the number of neuronal processes and contacts between them significantly increased. However, we have also found that the oxidative stress accompanying the schizophrenia can significantly reduce the valproic acid effect on the Ngf and Bdnf genes expression. The results of the study may be potentially useful for new schizophrenia therapy strategies development.

β-Amyloid Upregulates Intracellular Clusterin but not Secretory Clusterin in Primary Cultured Neurons and APP Mice

2017 ◽  
Vol 14 (11) ◽  
Author(s):  
Ping Wang ◽  
Keliang Chen ◽  
Yuehua Gu ◽  
Qihao Guo ◽  
Zhen Hong ◽  
...  
Keyword(s):  
Cultured Neurons ◽  
Β Amyloid ◽  
Primary Cultured Neurons

Biotinylation and Purification of Plasma Membrane-associated Proteins from Rodent Cultured Neurons

BIO-PROTOCOL ◽  
2016 ◽  
Vol 6 (10) ◽  
Author(s):  
Margarida Caldeira ◽  
Joana Ferreira ◽  
Ana Carvalho ◽  
Carlos Duarte
Keyword(s):  
Plasma Membrane ◽  
Cultured Neurons ◽  
Associated Proteins

scholarly journals The Adverse Pial Arteriolar and Axonal Consequences of Traumatic Brain Injury Complicated by Hypoxia and Their Therapeutic Modulation with Hypothermia in Rat

2009 ◽  
Vol 30 (3) ◽  
pp. 628-637 ◽  
Author(s):  
Guoyi Gao ◽  
Yasutaka Oda ◽  
Enoch P Wei ◽  
John T Povlishock
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Amyloid Precursor Protein ◽  
Vascular Reactivity ◽  
Axonal Damage ◽  
Precursor Protein ◽  
Moderate Hypothermia ◽  
Vascular Protection ◽  
Impact Acceleration ◽  
Cerebral Vascular

This study examined the effect of posttraumatic hypoxia on cerebral vascular responsivity and axonal damage, while also exploring hypothermia's potential to attenuate these responses. Rats were subjected to impact acceleration injury (IAI) and equipped with cranial windows to assess vascular reactivity to topical acetylcholine, with postmortem analyses using antibodies to amyloid precursor protein to assess axonal damage. Animals were subjected to hypoxia alone, IAI and hypoxia, IAI and hypoxia before induction of moderate hypothermia (33°C), IAI and hypoxia induced during hypothermic intervention, and IAI and hypoxia initiated after hypothermia. Hypoxia alone had no impact on vascular reactivity or axonal damage. Acceleration injury and posttraumatic hypoxia resulted in dramatic axonal damage and altered vascular reactivity. When IAI and hypoxia were followed by hypothermic intervention, no axonal or vascular protection ensued. However, when IAI was followed by hypoxia induced during hypothermia, axonal and vascular protection followed. When this same hypoxic insult followed the use of hypothermia, no benefit ensued. These studies show that early hypoxia and delayed hypoxia exert damaging axonal and vascular consequences. Although this damage is attenuated by hypothermia, this follows only when hypoxia occurs during hypothermia, with no benefit found if the hypoxic insult proceeds or follows hypothermia.

Sign in / Sign up

Export Citation Format

Share Document