Dopamine Receptors and Neurodegeneration

Rangel‐Barajas, Claudia; Coronel, Israel; Florán, Benjamí­n

doi:10.14336/ad.2015.0330

Cited by 182 publications

(86 citation statements)

References 209 publications

(233 reference statements)

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“…4) [168–170]. Growing evidence has shown, however, that activation of DA receptors is not only restricted to modulation of AC but also other complex transduction signaling pathways, depending on the brain area and any ongoing physiological and pathological conditions [171]. …”

Section: Dopamine Modulationmentioning

confidence: 99%

Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation

Rangel‐Barajas

Rebec

2016

JHD

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Aberrant communication between striatum, the main information processing unit of the basal ganglia, and cerebral cortex plays a critical role in the emergence of Huntington’s disease (HD), a fatal monogenetic condition that typically strikes in the prime of life. Although both striatum and cortex undergo substantial cell loss over the course of HD, corticostriatal circuits become dysfunctional long before neurons die. Understanding the dysfunction is key to developing effective strategies for treating a progressively worsening triad of motor, cognitive, and psychiatric symptoms. Cortical output neurons drive striatal activity through the release of glutamate, an excitatory amino acid. Striatal outputs, in turn, release γ-amino butyric acid (GABA) and exert inhibitory control over downstream basal ganglia targets. Ample evidence from transgenic rodent models points to dysregulation of corticostriatal glutamate transmission along with corresponding changes in striatal GABA release as underlying factors in the HD behavioral phenotype. Another contributor is dysregulation of dopamine (DA), a modulator of both glutamate and GABA transmission. In fact, pharmacological manipulation of DA is the only currently available treatment for HD symptoms. Here, we review data from animal models and human patients to evaluate the role of DA in HD, including DA interactions with glutamate and GABA within the context of dysfunctional corticostriatal circuitry.

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Section: Dopamine Modulationmentioning

confidence: 99%

Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation

Rangel‐Barajas

Rebec

2016

JHD

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“…Parkinson's disease (PD) is a chronic, progressive neurodegenerative disease characterized by the degeneration of midbrain dopaminergic neurons, resulting in motor dysfunction and disability [49,50]. The underlying mechanisms of neuronal loss associated with PD processes are currently unclear.…”

Section: Asics and Parkinson's Diseasementioning

confidence: 99%

Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

Zhou

Wang³

et al. 2016

Aging and disease

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“…Studies in numerous brain regions and cell types have established that D1 receptor activation is coupled to increased phosphorylation of a number of targets, including ERK1,2 and CREB (Gerfen et al, 2002; Voulalas et al, 2005; Beaulieu and Gainetdinov 2011; Xue et al, 2015), which can occur either directly or indirectly via D1 receptor-mediated activation of PKA (Rangel-Barajas, 2015). Our first approach was to determine whether in vivo exposure to the D1/5 agonist SKF 81297 (Gainetdinov et al, 2003; Lapointe and Guertin 2008; Ott et al, 2014; Lindenbach et al, 2015) would cause an increase in ERK or CREB phosphorylation in the PAG.…”

Section: Dopamine Receptor Function/signal Transduction In the Pagmentioning

confidence: 99%

Loss of dopamine D1 receptors and diminished D1/5 receptor-mediated ERK phosphorylation in the periaqueductal gray after spinal cord lesion

Voulalas

Jiang

et al. 2017

Neuroscience

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Neuropathic pain resulting from spinal cord injury is often accompanied by maladaptive plasticity of the central nervous system, including the opioid receptor-rich periaqueductal gray (PAG). Evidence suggests that sensory signaling via the PAG is robustly modulated by dopamine D1- and D2-like receptors, but the effect of damage to the spinal cord on D1 and D2 receptor protein expression and function in the PAG has not been examined. Here we show that 21 days after a T10 or C6 spinothalamic tract lesion, both mice and rats display a remarkable decline in the expression of D1 receptors in the PAG, revealed by western blot analysis. These changes were associated with a significant reduction in hindpaw withdrawal thresholds in lesioned animals compared to sham-operated controls. We investigated the consequences of diminished D1 receptor levels by quantifying D1-like receptor-mediated phosphorylation of ERK1,2 and CREB, events that have been observed in numerous brain structures. In naïve animals, western blot analysis revealed that ERK1,2, but not CREB phosphorylation was significantly increased in the PAG by the D1-like agonist SKF 81297. Using immunohistochemistry, we found that SKF 81297 increased ERK1,2 phosphorylation in the PAG of sham animals. However, in lesioned animals, basal pERK1,2 levels were elevated and did not significantly increase after exposure to SKF 81297. Our findings provide support for the hypothesis that molecular adaptions resulting in a decrease in D1 receptor expression and signaling in the PAG are a consequence of SCL.

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Dopamine Receptors and Neurodegeneration

Cited by 182 publications

References 209 publications

Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation

Dysregulation of Corticostriatal Connectivity in Huntington’s Disease: A Role for Dopamine Modulation

Novel Insights into Acid-Sensing Ion Channels: Implications for Degenerative Diseases

Loss of dopamine D1 receptors and diminished D1/5 receptor-mediated ERK phosphorylation in the periaqueductal gray after spinal cord lesion

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