Effects of Traumatic Stress in Adolescence on PTSD-like Behaviors, Dendrite Development, and H3K9me2/BDNF Expression in the Amygdala of Male Rats

Author(s):  
Mingyue Zhao ◽  
Zemeng Zhu ◽  
Haonan Li ◽  
Wei Wang ◽  
Shuyue Cheng ◽  
...  
2018 ◽  
Vol 7 (4) ◽  
pp. 239-245
Author(s):  
Shohei Dobashi ◽  
Chinatsu Aiba ◽  
Daisuke Ando ◽  
Masataka Kiuchi ◽  
Mitsuya Yamakita ◽  
...  

2021 ◽  
Author(s):  
Kimberly L. P. Long ◽  
Linda L. Chao ◽  
Yurika Kazama ◽  
Anjile An ◽  
Kelsey Y. Hu ◽  
...  

AbstractBackgroundIndividual reactions to traumatic stress vary dramatically, yet the biological basis of this variation remains poorly understood. Recent studies have demonstrated surprising plasticity of oligodendrocytes and myelin in the adult brain, providing a potential mechanism by which aberrant structural and functional changes arise in the brain following trauma exposure.MethodsWe tested the hypothesis that gray matter myelin contributes to traumatic stress-induced behavioral variation. We exposed adult rats to a single, severe stressor and used a multimodal approach to characterize avoidance, startle, and fear-learning behavior. We quantified oligodendrocyte and myelin content in multiple brain areas and compared these measures to behavioral metrics. We then induced overexpression of the oligodendrogenic transcription factor Olig1 in the adult rat dentate gyrus (DG) to test the potential, causal role of oligodendrogenesis in behavioral variation. Lastly, T1-/T2-weighted estimates of myelin were compared to trauma-induced symptom profiles in humans.ResultsOligodendrocytes and myelin in the DG of the hippocampus positively correlated with stress-induced avoidance behaviors in male rats. In contrast, myelin levels in the amygdala positively correlated with contextual fear learning. Olig1 overexpression increased place avoidance compared to control virus animals, indicating that increased oligodendrocyte drive in the DG is sufficient to induce an avoidance behavioral phenotype. Finally, variation in myelin correlated with trauma-induced symptom profiles in humans in a region-specific manner that mirrored our rodent findings.ConclusionsThese results demonstrate a species-independent relationship between region-specific, gray matter oligodendrocytes and myelin and differential behavioral phenotypes following traumatic stress exposure. This study provides a novel biological framework for understanding the mechanisms that underlie individual variance in sensitivity to traumatic stress.


2021 ◽  
Vol 15 ◽  
Author(s):  
Nawshaba Nawreen ◽  
Mark L. Baccei ◽  
James P. Herman

Post-traumatic stress disorder (PTSD) is a chronic, debilitating mental illness marked by abnormal fear responses and deficits in extinction of fear memories. The pathophysiology of PTSD is linked to decreased activation of the ventromedial prefrontal cortex (vmPFC). This study aims to investigate underlying functional changes in synaptic drive and intrinsic excitability of pyramidal neurons in the rodent homolog of the vmPFC, the infralimbic cortex (IL), following exposure to single prolonged stress (SPS), a paradigm that mimics core symptoms of PTSD in rats. Rats were exposed to SPS and allowed 1 week of recovery, following which brain slices containing the PFC were prepared for whole-cell patch clamp recordings from layer V pyramidal neurons in the IL. Our results indicate that SPS reduces spontaneous excitatory synaptic drive to pyramidal neurons. In addition, SPS decreases the intrinsic membrane excitability of IL PFC pyramidal cells, as indicated by an increase in rheobase, decrease in input resistance, hyperpolarization of resting membrane potential, and a reduction in repetitive firing rate. Our results suggest that SPS causes a lasting reduction in PFC activity, supporting a body of evidence linking traumatic stress with prefrontal hypoactivity.


2021 ◽  
Author(s):  
Evelin Cotella ◽  
Nawshaba Nawreen ◽  
Rachel Moloney ◽  
Susan Martelle ◽  
Kristen Oshima ◽  
...  

Abstract: Background: Stress during adolescence is usually associated with psychopathology later in life. However, under certain circumstances, developmental stress can promote an adaptive phenotype, allowing individuals to cope better with adverse situations in adulthood, thereby contributing to resilience. Methods: Sprague Dawley rats (50 males, 48 females) were subjected to adolescent chronic variable stress (adol CVS) for 2-weeks at PND45. At PND 85, a group was subjected to single prolonged stress (SPS). After a week, animals were evaluated in an auditory-cued fear conditioning paradigm and neuronal recruitment during reinstatement was assessed by Fos expression. Patch clamp electrophysiology (17-35 cells/group) was performed in male rats to examine physiological changes associated with resilience. Results: Adol CVS blocked fear potentiation evoked by SPS. We observed that SPS impaired extinction (males) and enhanced reinstatement (both sexes) of the conditioned freezing response. Prior adol CVS prevented both effects. SPS effects were associated with a reduction of infralimbic (IL) cortex neuronal recruitment after reinstatement in males and increased engagement of the central amygdala in females, both also prevented by adol CVS, suggesting different neurocircuits involved in generating resilience between sexes. We explored the mechanism behind reduced IL recruitment by studying the intrinsic excitability of IL pyramidal neurons. SPS reduced excitability of IL neurons and prior adol CVS prevented this effect. Conclusion: Our data indicate that adolescent stress can impart resilience to the effects of traumatic stress on neuroplasticity and behavior. Our data provide a mechanistic link behind developmental stress induced behavioral resilience and prefrontal (IL) cortical excitability.


2020 ◽  
Vol 10 (5) ◽  
pp. 270 ◽  
Author(s):  
Samuel J. Hogarth ◽  
Elvan Djouma ◽  
Maarten van den Buuse

Alcohol use disorder (AUD) is a detrimental disease that develops through chronic ethanol exposure. Reduced brain-derived neurotrophic factor (BDNF) expression has been associated with AUD and alcohol addiction, however the effects of activation of BDNF signalling in the brain on voluntary alcohol intake reinstatement and relapse are unknown. We therefore trained male and female Sprague Dawley rats in operant chambers to self-administer a 10% ethanol solution. Following baseline acquisition and progressive ratio (PR) analysis, rats were split into drug and vehicle groups during alcohol lever extinction. The animals received two weeks of daily IP injection of either the BDNF receptor, TrkB, agonist, 7,8-dihydroxyflavone (7,8-DHF), or vehicle. During acquisition of alcohol self-administration, males had significantly higher absolute numbers of alcohol-paired lever presses and a higher PR breakpoint. However, after adjusting for body weight, the amount of ethanol was not different between the sexes and the PR breakpoint was higher in females than males. Following extinction, alcohol-primed reinstatement in male rats was not altered by pretreatment with 7,8-DHF when adjusted for body weight. In contrast, in female rats, the weight-adjusted potential amount of ethanol, but not absolute numbers of active lever presses, was significantly enhanced by 7,8-DHF treatment during reinstatement. Analysis of spontaneous locomotor activity in automated photocell cages suggested that the effect of 7,8-DHF was not associated with hyperactivity. These results suggest that stimulation of the TrkB receptor may contribute to reward craving and relapse in AUD, particularly in females.


2018 ◽  
Vol 23 (6) ◽  
pp. 1233-1241 ◽  
Author(s):  
Chen Li ◽  
Alexandria C. White ◽  
Terri Schochet ◽  
Jacqueline F. McGinty ◽  
Kyle J. Frantz

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Chuting Li ◽  
Yuan Liu ◽  
Dexiang Liu ◽  
Hong Jiang ◽  
Fang Pan

Several types of microRNA (miRNA) overexpression in the brain are associated with stress. One of the targets of miR-34c is the stress-related corticotrophin releasing factor receptor 1 mRNA (CRFR1 mRNA). Here we will probe into the short-term effect and long-term effect of early adolescent traumatic stress on the expression of miR-34c and CRFR1 mRNA. Traumatic stress was established by electric foot shock for six consecutive days using 28-day rats. The anxiety-like behaviors, memory damage, CRFR1 protein, CRFR1 mRNA, and miR-34c expression were detected in our study. The results of our study proved that exposure to acute traumatic stress in early adolescent can cause permanent changes in neural network, resulting in dysregulation of CRFR1 expression and CRFR1 mRNA and miR-34c expression in hypothalamus, anxiety-like behavior, and memory impairment, suggesting that the miR-34c expression in hypothalamus may be an important factor involved in susceptibility to PTSD.


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