The ever-changing brain: Clinical implications

Dulcis, Davide

doi:10.1016/j.jchemneu.2015.10.003

Cited by 5 publications

(4 citation statements)

References 327 publications

(528 reference statements)

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“…The study results give an opportunity to formulate ideas on mechanisms of occurrence of the Electric Hypothalamus Test dynamics of female rats in different age groups. Probably the changes in neurophysiological characteristics in this part of the brain are due to the corresponding dynamics of synaptic plasticity (Nakamura et al, 1984;Patterson, 2015;Dulcis, 2016;Cole et al, 2017). From our point of view, the low level of differrentiation of mediator absorption postsynaptic receptors promotes a synchronized response to postsynaptic neurons.…”

Section: Discussionmentioning

confidence: 95%

Age-related characteristics of spectral bioelectric activity of the trophotropic zone of the hypothalamus in female rats

Mukvych¹,

Lyashenko²,

Lukashov³

2018

Regul. Mech. Biosyst.

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The purpose of the study was to determine the functional state of the trophotropic zone of the hypothalamus in female rats of different age groups according to bioelectric activity indices. Experiments were carried out on non-linear white outbred female rats. Animals were divided into IV groups: I group (2.5 months) the juvenile puberty period, II group (eight months) the young age of the reproductive period, III group (fourteen months) the mature age of the reproductive period, IV group (21 months) rats of presenile age of the pronounced senile changes period. Rats of the studied groups underwent Electric Hypothalamus Test (EGtG) of the trophotropic zone. The prevalence of low-frequency components of EGtG in female rats of the juvenile age and the domination of bioelectric activity in the delta range of the investigated hypothalamic region is determined. The young age in females was marked by an increase in all values of normalized spectral power, except the theta-like activity, which in turn was characterized by a possible decrease in the indices. In female rats, from young to presenile age, a gradual increase in the share of absolute power of high-frequency components of EGtG was observed, which was manifested in the functional activation of desynchronizing effect on bioelectric activity of the investigated hypothalamic region. There was an increase in theta-like and beta-like activity while there was a reduction in the percentage of alpha and especially delta wave power. In the female rats of the presenile age, the delta-like activity indices slightly recovered and exceeded those of mature female rats, theta and alpha-like activities underwent a significant decline in values and were represented by the lowest values, while beta-like activity was observed at the highest rates. However, it was precisely the mature female rats that showed a significant predominance of beta-like activity, which is evidence of the powerful desynchronizing mechanisms functioning. Electrophysiological indices indicate synaptic plasticity growth deficiency in female rats of the youngest age and factors of its degradation in those of presenile age, respectively. The power and the desynchronization rhythms representation increase is characteristic of the most productive age period with the most developed neurosynapticplasticity inherent to it.

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Section: Discussionmentioning

confidence: 95%

Age-related characteristics of spectral bioelectric activity of the trophotropic zone of the hypothalamus in female rats

Mukvych¹,

Lyashenko²,

Lukashov³

2018

Regul. Mech. Biosyst.

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“…These results led us to hypothesize that chronic stressinduced plasticity of serotonergic expression may occur in the DR and play a role in determining susceptibility or resilience to anhedonia. Neurotransmitter plasticity (Demarque and Spitzer, 2010;Dulcis and Spitzer, 2012;Dulcis, 2016) has not been explored previously in the DR or other brain regions in animal models of anhedonia.…”

Section: Introductionmentioning

confidence: 99%

Serotonergic Plasticity in the Dorsal Raphe Nucleus Characterizes Susceptibility and Resilience to Anhedonia

et al. 2019

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Chronic stress induces anhedonia in susceptible but not resilient individuals, a phenomenon observed in humans as well as animal models, but the molecular mechanisms underlying susceptibility and resilience are not well understood. We hypothesized that the serotonergic system, which is implicated in stress, reward, and antidepressant therapy, may play a role. We found that plasticity of the serotonergic system contributes to the differential vulnerability to stress displayed by susceptible and resilient animals. Stress-induced anhedonia was assessed in adult male rats using social defeat and intracranial self-stimulation, while changes in serotonergic phenotype were investigated using immunohistochemistry and in situ hybridization. Susceptible, but not resilient, rats displayed an increased number of neurons expressing the biosynthetic enzyme for serotonin, tryptophan-hydroxylase-2 (TPH2), in the ventral subnucleus of the dorsal raphe nucleus (DRv). Further, a decrease in the number of DRv glutamatergic (VGLUT3ϩ) neurons was observed in all stressed rats. This neurotransmitter plasticity is activity-dependent, as was revealed by chemogenetic manipulation of the central amygdala, a stress-sensitive nucleus that forms a major input to the DR. Activation of amygdalar corticotropin-releasing hormone (CRH)ϩ neurons abolished the increase in DRv TPH2ϩ neurons and ameliorated stress-induced anhedonia in susceptible rats. These findings show that activation of amygdalar CRHϩ neurons induces resilience, and suppresses the gain of serotonergic phenotype in the DRv that is characteristic of susceptible rats. This molecular signature of vulnerability to stress-induced anhedonia and the active nature of resilience could be targeted to develop new treatments for stress-related disorders like depression.

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“…Spitzer, 2010) may occur in the DR and play a role in determining susceptibility or resilience to anhedonia. Neurotransmitter plasticity (Dulcis and Spitzer, 2012;Dulcis, 2016) has not been explored previously in the DR or other brain regions in animal models of anhedonia.…”

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confidence: 99%

Serotonergic plasticity in the dorsal raphe nucleus characterizes susceptibility and resilience to anhedonia

Prakash

Stark

Keisler

et al. 2019

Preprint

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critical feedback on the research and Dr.Byung Kook Lim for his valuable feedback and the use of his slide-scanning microscope. ABSTRACTChronic stress induces anhedonia in susceptible, but not resilient individuals, a phenomenon observed in humans as well as animal models, but the molecular mechanisms underlying susceptibility and resilience are not well understood. We hypothesized that the serotonergic system, which is implicated in stress, reward and antidepressant therapy, may play a role. We found that plasticity of the serotonergic system contributes to the differential vulnerability to stress displayed by susceptible and resilient animals. Stress-induced anhedonia was assessed in SIGNIFICANCE STATEMENTDepression and other mental disorders can be induced by chronic or traumatic stressors.However, some individuals are resilient and do not develop depression in response to chronic stress. A complete picture of the molecular differences between susceptible and resilient individuals is necessary to understand how plasticity of limbic circuits is associated with the pathophysiology of stress-related disorders. Using a rodent model, our study identifies a novel molecular marker of susceptibility to stress-induced anhedonia, a core symptom of depression, and a means to modulate it. These findings will guide further investigation into cellular and circuit mechanisms of resilience, and the development of new treatments for depression.

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The ever-changing brain: Clinical implications

Cited by 5 publications

References 327 publications

Age-related characteristics of spectral bioelectric activity of the trophotropic zone of the hypothalamus in female rats

Age-related characteristics of spectral bioelectric activity of the trophotropic zone of the hypothalamus in female rats

Serotonergic Plasticity in the Dorsal Raphe Nucleus Characterizes Susceptibility and Resilience to Anhedonia

Serotonergic plasticity in the dorsal raphe nucleus characterizes susceptibility and resilience to anhedonia

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