Dopamine Release Impairment in Striatum after Different Levels of Cerebral Cortical Fluid Percussion Injury

Chen, Yuan-Hao; Huang, Eagle Yi Kung; Kuo, Tung Tai; Hsin, I.; Hoffer, Barry J.; Tsui, Pi Fen; Tsai, Jing Jr; Chou, Yu Ching; Chiang, Yung-Hsiao

doi:10.3727/096368914x683584

Cited by 26 publications

(27 citation statements)

References 49 publications

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“…Increasing evidence revealed the occurrence of neuronal apoptosis after brain injury [55]. Our results indicated the increase expression neuronal apoptotic markers including Bax, PARP1 and decrease the expression of Bcl-2 an anti-apoptotic protein.…”

Section: Discussionsupporting

confidence: 58%

Stimulation of dopamine D2 receptor via quinpirole protects against brain damage after brain injury in mice

Alam

Kim

et al. 2020

Preprint

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Backgroung Brain injury is a major risk factor for the development of chronic neurodegenerative diseases. The disease still lacks a potential candidate to treat brain injury associated neurodegeneration. In the present study we aims to investigate the expression of Dopamin D2 receptor in the cortical region as well as in striatum of the injured mouse brain and further explored the neuroprotective effects of selective D2R agonist quinpirole against brain injury-associated neuropathological events after brain injury.Methods In order to test our hypothesis, a normal mice were subjected into TBI mouse model by producing penetrating injury using scalpel blade. A dose of 1mg/kg of quinpirole was daily injected to the TBI mice via intraperitonally for 7 days after producing injury. Further, the immunoblots and immunohistochemistry analysis were performed for both in vivo and in vitro.Results Our biochemical and immunohistological results demonstrated that brain injury suppresses the expression levels of D2R and deregulate the downstream signaling molecules in the cortex and striatum afte TBI at day 7. Treatment with a selective D2R agonist quinpirole regulates GSK3-β/IL-1β/Akt signaling and reduced neuroinflamation after brain injury. Concomitantly, Quinpirole treatment regulated Blood brain-barrier breakdown, reduced neuronal apoptosis and regulated synaptic dysfunction after brain injury. This is the first evidence, which showed that quinpirole treatment reduced secondary brain injury-induced neuropathological evidence in the cortex via D2R/Akt/GSK3-β signaling pathway. Moreover, our in vitro results demonstrated that quinpirole reversed MCM-mediated deleterious effects and significantly regulated D2R/GSK3-β/Akt level in HT22 cells.Conclusion Our results suggest that regulation of Dopamine D2 receptor via quinpirole would be a promising therapeutic strategy against brain injury-induced neurodegeneration.

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Section: Discussionsupporting

confidence: 58%

Stimulation of dopamine D2 receptor via quinpirole protects against brain damage after brain injury in mice

Alam

Kim

et al. 2020

Preprint

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“…Microglia serves as the first defense of CNS and express a variety of neurotransmitter receptors so that neurotransmitter might have a significant influence on microglia functions ( Pocock and Kettenmann, 2007 ). Brain injury or emotional stress cause changes in DA or 5-HT release to the surroundings ( Kawahara et al, 1993 ; Chen et al, 2015 ). Microglia presumably exhibit differential responses to DA or 5-HT depending on their activation status.…”

Section: Discussionmentioning

confidence: 99%

Differential Regulation of Adhesion and Phagocytosis of Resting and Activated Microglia by Dopamine

Yang

Chen

Pathak

et al. 2018

Front. Cell. Neurosci.

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Microglia, the immune competent cells of the central nervous system (CNS), normally exist in a resting state characterized by a ramified morphology with many processes, and become activated to amoeboid morphology in response to brain injury, infection, and a variety of neuroinflammatory stimuli. Many studies focused on how neurotransmitters affect microglia activation in pathophysiological circumstances. In this study, we tried to gain mechanistic insights on how dopamine (DA) released from neurons modulates cellular functions of resting and activated microglia. DA induced the reduction of the number of cellular processes, the increase of cell adhesion/spreading, and the increase of vimentin filaments in resting primary and BV2 microglia. In contrast to resting cells, DA downregulated the cell spreading and phagocytosis of microglia activated by LPS. DA also significantly downregulated ERK1/2 phosphorylation in activated microglia, but not in resting microglia. Downregulation of ERK1/2 by DA in activated microglia required receptor signaling. In contrast, we found a significant increase of p38MAPK activity by DA treatment in resting, but not in activated microglia. These latter effects required the uptake of DA through the high-affinity transporter but did not require receptor signaling. Activation of p38MAPK resulted in the increase of focal adhesion number via phosphorylation of paxillin at Ser83. These results indicate that DA might have a differential, depending upon the activation stage of microglia, impact on cellular functions such as adhesion and phagocytosis.

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“…Detrimental outcomes are associated with variants of the human dopamine transporter (DAT) and dopamine D2 receptor genes (Wagner et al, 2014;Treble-Barna et al, 2017). Experimental injuries result in lower levels of DAT, and consequently, reduced dopamine release and firing rates (Wagner et al, 2005;Shimada et al, 2014;Chen et al, 2015). Moreover, dopaminergic therapies may improve symptoms in brain-injured populations, including response disinhibition, executive function, and motivation (Powell et al, 1996;Beers et al, 2005;Kraus et al, 2005;Moreno-L opez et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Cocaine self‐administration is increased after frontal traumatic brain injury and associated with neuroinflammation

Haar

Ferland

Kaur

et al. 2018

Eur J of Neuroscience

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Traumatic brain injury (TBI) has been linked to the development of numerous psychiatric diseases, including substance use disorder. However, it can be difficult to ascertain from clinical data whether the TBI is cause or consequence of increased addiction vulnerability. Surprisingly few studies have taken advantage of animal models to investigate the causal nature of this relationship. In terms of a plausible neurobiological mechanism through which TBI could magnify the risk of substance dependence, numerous studies indicate that TBI can cause widespread disruption to monoaminergic signaling in striatal regions, and also increases neuroinflammation. In the current study, male Long-Evans rats received either a mild or severe TBI centered over the frontal cortex via controlled cortical impact, and were subsequently trained to self-administer cocaine over 10 6-hour sessions. At the end of the study, markers of striatal dopaminergic function, and levels of inflammatory cytokine levels in the frontal lobes, were assessed via western blot and multiplex ELISA, respectively. There was significantly higher cocaine intake in a subset of animals with either mild or severe TBI. However, many animals within both TBI groups failed to acquire self-administration. Principal components analysis suggested that both dopaminergic and neuroinflammatory proteins were associated with overall cocaine intake, yet only an inflammatory component was associated with acquisition of self-administration, suggesting neuroinflammation may make a more substantial contribution to the likelihood of drug-taking. Should neuroinflammation play a causal role in mediating TBI-induced addiction risk, anti-inflammatory therapy may reduce the likelihood of substance abuse in TBI populations.

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Dopamine Release Impairment in Striatum after Different Levels of Cerebral Cortical Fluid Percussion Injury

Cited by 26 publications

References 49 publications

Stimulation of dopamine D2 receptor via quinpirole protects against brain damage after brain injury in mice

Stimulation of dopamine D2 receptor via quinpirole protects against brain damage after brain injury in mice

Differential Regulation of Adhesion and Phagocytosis of Resting and Activated Microglia by Dopamine

Cocaine self‐administration is increased after frontal traumatic brain injury and associated with neuroinflammation

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