Stress-induced plasticity and functioning of ventral tegmental dopamine neurons

Douma, Erik H.; Kloet, E. R. de

doi:10.1016/j.neubiorev.2019.10.015

Cited by 177 publications

(139 citation statements)

References 419 publications

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“…Previous studies have shown that both mitochondrial function 81 and glucocorticoid actions 82 , 83 in the NAc is important for the establishment of social dominance in rats, a considered vulnerability factor for depression 84 . Moreover, the GR implicated in the mesocorticolimbic dopamine system with chronic stress vulnerability 85 , 86 , and showed that the GR has the capability to translocate into brain mitochondria 68 , 87 , 88 and to bind on the mitochondrial genome 56 , 89 in a glucocorticoid-dependent manner 56 . It will also be important to test whether mitochondrial-targeted interventions known to ameliorate stress and anxiety responses 54 , 90 – 92 would reverse both the behavioral and mtDNA transcriptional changes observed in stress-vulnerable mice.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial gene signature in the prefrontal cortex for differential susceptibility to chronic stress

Weger

Alpern

Cherix

et al. 2020

Sci Rep

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Mitochondrial dysfunction was highlighted as a crucial vulnerability factor for the development of depression. However, systemic studies assessing stress-induced changes in mitochondria-associated genes in brain regions relevant to depression symptomatology remain scarce. Here, we performed a genome-wide transcriptomic study to examine mitochondrial gene expression in the prefrontal cortex (PFC) and nucleus accumbens (NAc) of mice exposed to multimodal chronic restraint stress. We identified mitochondria-associated gene pathways as most prominently affected in the PFC and with lesser significance in the NAc. A more detailed mitochondrial gene expression analysis revealed that in particular mitochondrial DNA-encoded subunits of the oxidative phosphorylation complexes were altered in the PFC. The comparison of our data with a reanalyzed transcriptome data set of chronic variable stress mice and major depression disorder subjects showed that the changes in mitochondrial DNA-encoded genes are a feature generalizing to other chronic stress-protocols as well and might have translational relevance. Finally, we provide evidence for changes in mitochondrial outputs in the PFC following chronic stress that are indicative of mitochondrial dysfunction. Collectively, our work reinforces the idea that changes in mitochondrial gene expression are key players in the prefrontal adaptations observed in individuals with high behavioral susceptibility and resilience to chronic stress.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial gene signature in the prefrontal cortex for differential susceptibility to chronic stress

Weger

Alpern

Cherix

et al. 2020

Sci Rep

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“…However, chronic stress can also lead to atrophy of the ventral tegmental area system [50]. It has been hypothesized that these opposing outcomes might be due to a different nature of the stressors, the heterogeneity of ventral tegmental area cells, or the time of day when the experiments were performed [51]. Interestingly, it has been found that the level of Ser9-phosphorylated GSK3β in the ventral tegmental area and other reward-related brain structures in naïve rats shows significant circadian rhythmicity [52].…”

Section: Gsk3β Expression Profile and Activity In Depressionmentioning

confidence: 99%

GSK3β: A Master Player in Depressive Disorder Pathogenesis and Treatment Responsiveness

Duda

Hajka

Wójcicka

et al. 2020

Cells

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Glycogen synthase kinase 3β (GSK3β), originally described as a negative regulator of glycogen synthesis, is a molecular hub linking numerous signaling pathways in a cell. Specific GSK3β inhibitors have anti-depressant effects and reduce depressive-like behavior in animal models of depression. Therefore, GSK3β is suggested to be engaged in the pathogenesis of major depressive disorder, and to be a target and/or modifier of anti-depressants' action. In this review, we discuss abnormalities in the activity of GSK3β and its upstream regulators in different brain regions during depressive episodes. Additionally, putative role(s) of GSK3β in the pathogenesis of depression and the influence of anti-depressants on GSK3β activity are discussed.Cells 2020, 9, 727 2 of 26 any of the groups listed above. Additionally, electroconvulsive therapy, conducted for the first time in 1938, is still widely used in the treatment of MDD, especially in its drug-refractory form [5].Although the monoaminergic hypothesis has led to the invention of many successful therapeutic strategies based on the elevation of levels of NA and 5-HT in the synaptic cleft, it does not explain the anti-depressant effect of lithium and the rapid action of ketamine in the treatment of mood disorders [6]. Therefore, factors other than neurotransmission must be taken into consideration in the context of the MDD pathogenesis. One of them is glycogen synthase kinase 3β (GSK3β) signaling. Glycogen Synthase Kinase 3βGSK3 was isolated in 1980, from rabbit skeletal muscle, and described as a highly specific serine/threonine kinase for glycogen synthase [7]. There are two isozymes of GSK3, α and β, and both are expressed at similar levels in the mouse brain [8]. In the human brain, the β isozyme predominates [9]. Therefore, GSK3β is expected to be crucial for the human central nervous system functioning. The activity of GSK3β is regulated positively and negatively by phosphorylation on Tyr216 and Ser9, respectively [10,11]. Whereas phosphorylation of the residue Tyr216 occurs during the GSK3β translation process and results in a synthesis of the fully activated kinase, Ser9 phosphorylation seems to be the main regulatory modification during the enzyme lifespan [12]. Ser9-phosphorylated GSK3β remains inhibited, and dephosphorylation of the residue results in the disinhibition (activation) of the kinase.GSK3β is part of numerous cellular signaling pathways, and its activity can be regulated, directly or indirectly, by several kinases, phosphatases, and proteases. The wide spectrum of GSK3β substrates, including transcription factors, glycolytic enzymes, pro-and anti-apoptotic factors, mitochondrial channels, membrane receptors, and cytoskeleton-associated proteins, makes GSK3β a central point of the cell homeostasis maintenance [13]. The activity of GSK3β affects energy metabolism, cell survival, proliferation, apoptosis, membrane polarity, internalization of the synaptic receptors, neuroplasticity, neurotransmission, amyloid processing, and many other processes [13].Ex...

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“…A large body of literature has shown that many PD patients experience cognitive and motor inflexibility, as a result of nigrostriatal dopamine depletion that forms the pathophysiological substrate of PD [2,3]. Furthermore, it has been hypothesized that dopamine-dependent adaptation is a requirement for successful coping that, when deficient, leads to a sense of loss of control and increased psychological stress [4]. This may explain why stress-related psychiatric symptoms such as anx-352 R.C.…”

mentioning

confidence: 99%

The Impact of the COVID-19 Pandemic on Parkinson’s Disease: Hidden Sorrows and Emerging Opportunities

Helmich

Bloem

2020

JPD

276

325

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In the past few months, the world seems to have come to a virtual standstill. As the SARS-CoV-2 virus continues to spread across the globe, many countries have taken drastic measures to slow down infection rates. These include social distancing, and in some countries a complete lock-down of social and economic life. The impact of the corona virus disease (COVID-19) crisis is evident, on the lives of the worst affected families, our healthcare systems, and the world economy. There are particular concerns around the increased vulnerability of patients living with a chronic disease, and this also includes neurological conditions like Parkinson's disease (PD). Indeed, PD is more common in the elderly, and PD can compromise the respiratory system, as reflected among others by the increased risk of pneumonia that is present in patients with advanced PD. Although documented reports are thus far lacking, it is conceivable that having a diagnosis of PD is a risk factor for worse respiratory complications or even an unfavorable outcome after a COVID-19 infection. This "immediate" impact of a COVID-19 infection for people living

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Stress-induced plasticity and functioning of ventral tegmental dopamine neurons

Cited by 177 publications

References 419 publications

Mitochondrial gene signature in the prefrontal cortex for differential susceptibility to chronic stress

Mitochondrial gene signature in the prefrontal cortex for differential susceptibility to chronic stress

GSK3β: A Master Player in Depressive Disorder Pathogenesis and Treatment Responsiveness

The Impact of the COVID-19 Pandemic on Parkinson’s Disease: Hidden Sorrows and Emerging Opportunities

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