Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex

Xing, Bo; Li, Yanchun; Gao, Wen-Jun

doi:10.1016/j.brainres.2016.01.005

Cited by 154 publications

(140 citation statements)

References 239 publications

(295 reference statements)

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“…Catecholamines are processed by three main nuclei (A8-retrobulbal, A9-substantia nigra pars compacta, A10-ventral tegmental area) arranged in the mesencephalic region where the mesostriatal, mesolimbic and mesocortical pathways are organized [104,105]. Midbrain dopaminergic neurons in the ventral tegmental area and noradrenergic neurons in the locus coeruleus are major sources of dopamine and noradrenaline to the prefrontal cortex, where these amines regulate cognition, behavior, and psychomotor function [106,107]. Noradrenaline, adrenaline, dopamine and serotonin play a central role in CNS and gut pathophysiology.…”

Section: Novel Treatmentsmentioning

confidence: 99%

Parkinson’s Disease: From Pathogenesis to Pharmacogenomics

Cacabelos

2017

IJMS

451

300

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Parkinson’s disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer’s disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson’s disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects. Parkinson’s disease neuropathology is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta, with widespread involvement of other central nervous system (CNS) structures and peripheral tissues. Pathogenic mechanisms associated with genomic, epigenetic and environmental factors lead to conformational changes and deposits of key proteins due to abnormalities in the ubiquitin–proteasome system together with dysregulation of mitochondrial function and oxidative stress. Conventional pharmacological treatments for PD are dopamine precursors (levodopa, l-DOPA, l-3,4 dihidroxifenilalanina), and other symptomatic treatments including dopamine agonists (amantadine, apomorphine, bromocriptine, cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine), monoamine oxidase (MAO) inhibitors (selegiline, rasagiline), and catechol-O-methyltransferase (COMT) inhibitors (entacapone, tolcapone). The chronic administration of antiparkinsonian drugs currently induces the “wearing-off phenomenon”, with additional psychomotor and autonomic complications. In order to minimize these clinical complications, novel compounds have been developed. Novel drugs and bioproducts for the treatment of PD should address dopaminergic neuroprotection to reduce premature neurodegeneration in addition to enhancing dopaminergic neurotransmission. Since biochemical changes and therapeutic outcomes are highly dependent upon the genomic profiles of PD patients, personalized treatments should rely on pharmacogenetic procedures to optimize therapeutics.

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Section: Novel Treatmentsmentioning

confidence: 99%

Parkinson’s Disease: From Pathogenesis to Pharmacogenomics

Cacabelos

2017

IJMS

451

300

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“…In support of a role for VTA to NAc dopamine in processes that prepare or anticipate the biological significance of the aggressive bout, rats subjected to ten days of repeated aggression (beginning on the same time each day) display increases in NAc dopamine on day eleven at the time a confrontation would have occurred, even when no conspecific was introduced (Ferrari et al 2003). Interestingly, dopamine release in the mPFC, which has been shown to be important in controlling working memory and attention (Xing et al 2016), appears to reach its peak during aggression onset (van Erp and Miczek 2000). These temporal variations in dopamine signaling between NAc and mPFC circuits indicate that VTA dopamine may play a dynamic and multifaceted role in controlling various behavioral components of aggressive behavior, from encoding salience and attention to strengthening motivation.…”

Section: Regulation Of Aggression and Aggression Reward By Lhb Targetsmentioning

confidence: 99%

An emerging role for the lateral habenula in aggressive behavior

Flanigan

Aleyasin

Takahashi

et al. 2017

Pharmacology Biochemistry and Behavior

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Inter-male aggression is an essential component of social behavior in organisms from insects to humans. However, when expressed inappropriately, aggression poses significant threats to the mental and physical health of both the aggressor and the target. Inappropriate aggression is a common feature of numerous neuropsychiatric disorders in humans and has been hypothesized to result from the atypical activation of reward circuitry in response to social targets. The lateral habenula (LHb) has recently been identified as a major node of the classical reward circuitry and inhibits the release of dopamine from the midbrain to signal negative valence. Here, we discuss the evidence linking LHb function to aggression and its valence, arguing that strong LHb outputs to the ventral tegmental area (VTA) and the dorsal raphe nucleus (DRN) are likely to play roles in aggression and its rewarding components. Future studies should aim to elucidate how various inputs and outputs of the LHb shape motivation and reward in the context of aggression.

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“…Dopamine Receptor 2 (D2R) inhibits AKT via activation of β-arrestin 2/PP2A complex and leads to GSK3β activation [33].GSK3β activity can also be affected by 5-HT signaling. Stimulation of 5-HT 1 and 5-HT 7 activates the PI3K/AKT pathway and thus, increases Ser9 phosphorylation in GSK3β, while activation of 5-HT 2A R has the opposite effect [34,35].NA inhibits GSK3β activity acting through the α1A-adrenergic receptor (α1AAR) and stimulating phosphorylation of GSK3β Ser9 via protein kinase C (PKC) [36], and through α2and β-adrenergic receptors (α2AR and βAR) via PKA [37,38].The relationship between GSK3β and neurotransmitters is schematically presented in Figure 1. Concluding, GSK3β is a hub that links different molecular pathways within a cell.…”

mentioning

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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Norepinephrine versus dopamine and their interaction in modulating synaptic function in the prefrontal cortex

Cited by 154 publications

References 239 publications

Parkinson’s Disease: From Pathogenesis to Pharmacogenomics

Parkinson’s Disease: From Pathogenesis to Pharmacogenomics

An emerging role for the lateral habenula in aggressive behavior

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

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