Huntington's disease (HD) is a noncurable and progressive autosomal-dominant neurodegenerative disorder that results from a polyglutamine expansion in the amino-terminal region of the huntingtin protein. The generation of rodent HD models has revealed that cellular dysfunction, rather than cell death alone, occurs early in the disease progression, appearing even before overt symptom onset. Much evidence has now established that dysfunction of the corticostriatal circuit is key to HD symptomology. In this article, we summarize the most current findings that implicate glutamate, dopamine and calcium signaling in this system and discuss how they work in concert to disrupt corticostriatal function. In addition, we highlight therapeutic strategies related to altered corticostriatal signaling in HD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184508 | PMC |
| http://dx.doi.org/10.2217/fnl.10.41 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Update on the connectivity of the paraventricular nucleus of the thalamus and its position within limbic corticostriatal circuits.
Neurosci Biobehav Rev
December 2024
Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba R3E 0W2, Canada. Electronic address:
The paraventricular nucleus of the thalamus (PVT) is generating interest because evidence establishes a role for this midline thalamic nucleus in behavior. Early tracing studies demonstrated that afferent fibers from the PVT and limbic cortex converge with dopamine fibers within subcompartments of the ventral striatum. Subsequent tracing studies expanded on these observations by establishing that the PVT provides a dense projection to a continuum of striatal-like regions that include the nucleus accumbens and the extended amygdala.
View Article and Find Full Text PDFCatecholaminergic Modulation of Large-Scale Network Dynamics Is Tied to the Reconfiguration of Corticostriatal Connectivity.
Hum Brain Mapp
December 2024
Biomedical Research Center, National Institute on Drug Abuse Intramural Research Program, Baltimore, Maryland, USA.
Large-scale brain network function is critical for healthy cognition, yet links between such network function, neurochemistry, and smaller-scale neurocircuitry are unclear. Here, we evaluated 59 healthy individuals using resting-state fMRI to determine how network-level temporal dynamics were impacted by two well-characterized pharmacotherapies targeting catecholamines: methylphenidate (20 mg) and haloperidol (2 mg)-administered via randomized, double-blind, placebo-controlled design. Network temporal dynamic changes were tested for links with drug-induced alterations in complex corticostriatal connections as this circuit is a primary site of action for both drugs.
View Article and Find Full Text PDFStress during early life influences brain development and can affect social, motor, and emotional processes. We describe a striking sex difference in the effects of early life stress (ELS), which produces anhedonia and anxiety-like behaviors in female adolescent mice, as reported previously, but repetitive behavioral pathology and social deficits in male adolescent mice. Notably, this parallels sex differences seen in the prevalence of psychiatric symptoms: depression and anxiety disorders are more common in girls and women, whereas neurodevelopmental disorders like autism spectrum disorder and Tourette syndrome are markedly more common in boys and men.
View Article and Find Full Text PDFEAAT2 Activation Regulates Glutamate Excitotoxicity and Reduces Impulsivity in a Rodent Model of Parkinson's Disease.
Mol Neurobiol
December 2024
Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, 19129, USA.
Article Synopsis
- - Parkinson's disease involves the loss of dopamine-producing neurons, leading to disrupted brain circuitry that negatively impacts both cognitive function and decision-making behavior due to elevated glutamate levels.
- - The study investigates GTS467, a drug that activates an important transporter responsible for clearing excess glutamate, hypothesizing it could mitigate cognitive deficits without increasing impulsivity in PD patients.
- - Chronic treatment with GTS467 in rat models showed improved task performance and reduced impulsive actions, alongside beneficial changes in glutamate levels and gene expression related to brain health, supporting its potential as a therapeutic option for PD.
Corticostriatal glutamate-mediated dynamic therapeutic efficacy of electroacupuncture in a parkinsonian rat model.
Clin Transl Med
December 2024
Department of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China.
Background: Motor impairments are the defining cardinal features of Parkinson's disease (PD), resulting from malfunction of the cortico-basal ganglia circuit. Clinical data have demonstrated that electroacupuncture (EA) stimulation may benefit motor symptoms in PD without adverse effects. However, the specific effects of EA on PD and the underlying mechanisms remain largely unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!