Impact of Traumatic Brain Injury on Dopaminergic Transmission

Chen, Yuan-Hao; Huang, Eagle Yi Kung; Kuo, Tung Tai; Miller, Jonathan P.; Chiang, Yung Hsiao; Hoffer, Barry J.

doi:10.1177/0963689717714105

Cited by 50 publications

(37 citation statements)

References 133 publications

(148 reference statements)

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“…Factors, such as route of cocaine administration, methods of extraction, and potential co-morbid mental disorders in human subjects, such as major depression or bipolar disorder (See Table S1 in 1 ). These differences may reflect neuropsychopathological differences in genotype and phenotype regulation patterns in the NAc and in MSN subtypes linked to broad forms of neuropathology [9][10][11][47][48][49] . Additionally, the analysis in bulk tissue could mask cell subtype specific effects that we have observed in rodent tissue.…”

Section: Resultsmentioning

confidence: 99%

Cocaine-induced neuron subtype mitochondrial dynamics through Egr3 transcriptional regulation

Cole

Chandra

Harris

et al. 2020

Preprint

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AbstractMitochondrial function is required for brain energy homeostasis and neuroadaptation. Recent studies demonstrated that cocaine affects mitochondrial dynamics within the nucleus accumbens (NAc) and mitochondria are differentially regulated by cocaine in dopamine receptor-1 (D1) containing medium spiny neurons (MSNs) vs dopamine receptor-2 (D2)-MSNs. Here, it is demonstrated that cocaine enhances binding of the transcription factor, early growth response factor 3 (Egr3), to nuclear genes involved in mitochondrial function and dynamics. Further, cocaine exposure regulates mRNA of these mitochondria-associated nuclear genes in both contingent or noncontingent cocaine administration and in both rodent models and human postmortem tissue. Interestingly, several mitochondrial genes showed distinct profiles of expression in D1-MSNs vs D2-MSNs, with cocaine exposure generally increasing mitochondrial-associated nuclear gene expression in D1-MSNs vs suppression in D2-MSNs. Subsequent experiments demonstrated that Egr3 overexpression in D1-MSNs enhances the expression of several mitochondrial-associated nuclear genes. By contrast, blunting Egr3 expression blocks cocaine enhancement of the mitochondrial-associated transcriptional coactivator, peroxisome proliferator-activated receptor gamma coactivator (PGC1α), and the mitochondrial fission molecule, dynamin related protein 1 (Drp1). Finally, reducing Egr3 expression attenuates the cocaine-induced enhancement of small-sized mitochondria, demonstrating that Egr3 regulates mitochondrial morphological adaptations. Collectively, these studies demonstrate cocaine exposure impacts Egr3 transcriptional regulation of mitochondria-related nuclear gene transcripts and mitochondrial dynamics, with implications for mechanisms underlying neuronal function and plasticity occurring with cocaine exposure.

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Section: Resultsmentioning

confidence: 99%

Cocaine-induced neuron subtype mitochondrial dynamics through Egr3 transcriptional regulation

Cole

Chandra

Harris

et al. 2020

Preprint

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“…Though still incompletely understood, the neuropathology of traumatic brain injury (TBI) involve direct anatomical damage (primary injury) and disruption of both functional electrical and chemical transmission (Pistoia et al, 2010;Chen et al, 2017). This "secondary phase", evolving for weeks and even months after the mechanical injury (diffuse axonal injury) is characterized by persistent neuroinflammation, oxidative stress, neurotrophic factors changes and apoptosis of neurons and glia (Chen et al, 2017). open-label pilot study (Fridman et al, 2009;.…”

Section: Disorders Of Consciousnessmentioning

confidence: 99%

“…Nevertheless, these results are not based on a rigorous double-blind placebo-controlled design and are only confined to a few subjects. Larger samples are needed, especially since patients' heterogeneity regarding injuries, extent of lesion and management, make interpretation difficult (Pistoia et al, 2010;Chen et al, 2017). A prospective, multi-center, randomized, double-blind, placebo-controlled study of the safety and efficacy of apomorphine hydrochloride (NH001, up to 6 mg/h for 12 h a day) in VS and MCS following TBI was launched in 2010 and expected to enroll 76 patients (ClinicalTrials.gov Identifier: NCT00761228), but it is currently suspended 4 .…”

Section: Disorders Of Consciousnessmentioning

confidence: 99%

“…TBI can induce long-term disorders of consciousness (DOC), including vegetative state (VS) and minimally conscious state (MCS), characterized by arousal but lack of awareness(Pistoia et al, 2010). VS and MCS (to a lesser extent) stem from a disconnection of several cortical networks associated with functional changes at the neurotransmitter level(Pistoia et al, 2010;Chen et al, 2017). More precisely, alterations in monoamine signaling and dopaminergic abnormalities (in the nigrostriatal and mesolimbic systems) are documented in a significant proportion of patients suffering from moderate to severe TBI(Fridman et al, 2010;Chen et al, 2017).…”

mentioning

confidence: 99%

“…VS and MCS (to a lesser extent) stem from a disconnection of several cortical networks associated with functional changes at the neurotransmitter level(Pistoia et al, 2010;Chen et al, 2017). More precisely, alterations in monoamine signaling and dopaminergic abnormalities (in the nigrostriatal and mesolimbic systems) are documented in a significant proportion of patients suffering from moderate to severe TBI(Fridman et al, 2010;Chen et al, 2017). Therapeutic goals (improvement of awareness levels) and clinical recovery (recovery of consciousness) involve the functional restoration of disrupted networks(Chen et al, 2017;Pistoia et al, 2010).…”

mentioning

confidence: 99%

See 2 more Smart Citations

New tricks for an old dog: A repurposing approach of apomorphine

Auffret

Drapier

Vérin

2019

European Journal of Pharmacology

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Apomorphine is a 150-year old nonspecific dopaminergic agonist, currently indicated for treating motor fluctuations in Parkinson's disease. At the era of drug repurposing, its pleiotropic biological functions suggest other possible uses. To further explore new therapeutic and diagnostic applications, the available literature up to July 2018 was reviewed using the PubMed and Google Scholar databases. As many of the retrieved articles consisted of case reports and preclinical studies, we adopted a descriptive approach, tackling each area of research in turn, to give a broad overview of the potential of apomorphine. Apomorphine may play a role in neurological diseases like restless legs syndrome, Huntington's chorea, amyotrophic lateral sclerosis, Alzheimer's disease and disorders of consciousness, but also in sexual disorders, neuroleptic malignant(-like) syndrome and cancer. Further work is needed in both basic and clinical research; current developments in novel delivery strategies and apomorphine derivatives are expected to open the way.

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Ongoing effects of preterm birth on the dopaminergic and noradrenergic pathways in the frontal cortex and hippocampus of guinea pigs

Moloney,

Palliser,

Dyson

et al. 2024

Developmental Neurobiology

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Children born preterm have an increased likelihood of developing neurobehavioral disorders such as attention‐deficit hyperactivity disorder (ADHD) and anxiety. These disorders have a sex bias, with males having a higher incidence of ADHD, whereas anxiety disorder tends to be more prevalent in females. Both disorders are underpinned by imbalances to key neurotransmitter systems, with dopamine and noradrenaline in particular having major roles in attention regulation and stress modulation. Preterm birth disturbances to neurodevelopment may affect this neurotransmission in a sexually dimorphic manner. Time‐mated guinea pig dams were allocated to deliver by preterm induction of labor (gestational age 62 [GA62]) or spontaneously at term (GA69). The resultant offspring were randomized to endpoints as neonates (24 h after term‐equivalence age) or juveniles (corrected postnatal day 40, childhood equivalence). Relative mRNA expressions of key dopamine and noradrenaline pathway genes were examined in the frontal cortex and hippocampus and quantified with real‐time PCR. Myelin basic protein and neuronal nuclei immunostaining were performed to characterize the impact of preterm birth. Within the frontal cortex, there were persisting reductions in the expression of dopaminergic pathway components that occurred in preterm males only. Conversely, preterm‐born females had increased expression of key noradrenergic receptors and a reduction of the noradrenergic transporter within the hippocampus. This study demonstrated that preterm birth results in major changes in dopaminergic and noradrenergic receptor, transporter, and synthesis enzyme gene expression in a sex‐ and region‐based manner that may contribute to the sex differences in susceptibility to neurobehavioral disorders. These findings highlight the need for the development of sex‐based treatments for improving these conditions.

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Impact of Traumatic Brain Injury on Dopaminergic Transmission

Cited by 50 publications

References 133 publications

Cocaine-induced neuron subtype mitochondrial dynamics through Egr3 transcriptional regulation

Cocaine-induced neuron subtype mitochondrial dynamics through Egr3 transcriptional regulation

New tricks for an old dog: A repurposing approach of apomorphine

Ongoing effects of preterm birth on the dopaminergic and noradrenergic pathways in the frontal cortex and hippocampus of guinea pigs

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