Basal Ganglia Pathophysiology
Organisational unit: Research group
Research areas and keywords
UKÄ subject classification
The basal ganglia are a group of interconnected brain nuclei involved in action control. Loss or dysfunction of neurons within the basal ganglia cause some typical motor symptoms, such as poverty of movement (akinesia) or abnormal involuntary movements (dyskinesia). Parkinson´s disease (PD; prevalence ~ 1% in the population over 55 years of age) is the most common neurodegenerative disease affecting the basal ganglia. The typical lesion in PD consists in a loss of dopamine neurons that are located in the substantia nigra. Pharmacological dopamine replacement with L-DOPA remains the most effective treatment for PD. However, this treatment causes severe long-term complications, such as dyskinesia (abnormal involuntary movements). Novel treatment strategies for PD, such as intracerebral neural transplants, can also cause disabling dyskinesias.
Our research explores molecular and cellular plasticity in the basal ganglia after damage and/or pharmacological treatment. Our major lines of investigation address the mechanisms of symptom progression and treatment-related dyskinesias in rodent models of Parkinson´s disease. These studies take advantage of articulate behavioural testing routines for rats and mice that we have developed. We are currently studying the role of specific signaling molecules and transcription factors in L-DOPA-induced dyskinesia. We are also studying changes in transmitter release in the basal ganglia in rats that develop dyskinesia following intrastriatal neural transplants and/or chronic treatment with L-DOPA. We are further evaluating the therapeutic potential of novel pharmacological agents that act on non-dopaminergic receptor systems. Our research will contribute to the development of novel therapies for Parkinson´s Disease and other disorders of the basal ganglia.
Recent research outputs
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Chemogenetic stimulation of striatal projection neurons modulates responses to Parkinson's disease therapyCristina Alcacer, Laura Andreoli, Irene Sebastianutto, Johan Jakobsson, Tim Fieblinger & Angela Cenci Nilsson 2017 Feb 1 In : Journal of Clinical Investigation. 127, 2, p. 720-734 15 p.
Research output: Contribution to journal › Article