TY - JOUR
T1 - The role of neuroplasticity in dopaminergic therapy for Parkinson disease
AU - Zhuang, Xiaoxi
AU - Mazzoni, Pietro
AU - Kang, Un Jung
N1 - Funding Information:
The authors were supported by the NIH (NS062425 and NS070269 to X. Zhuang, NS052804 to P. Mazzoni, and NS062425 and NS064865 to U. J. Kang), the American Parkinson Disease Association (X. Zhuang and U. J. Kang), the Parkinson’s Disease Foundation (P. Mazzoni), and the Michael J. Fox Foundation for Parkinson’s Research (U. J. Kang).
PY - 2013/5
Y1 - 2013/5
N2 - Dopamine replacement is a mainstay of therapeutic strategies for Parkinson disease (PD). The motor response to therapy involves an immediate improvement in motor function, known as the short-duration response (SDR), followed by a long-duration response (LDR) that develops more slowly, over weeks. Here, we review evidence in patients and animal models suggesting that dopamine-dependent corticostriatal plasticity, and retention of such plasticity in the absence of dopamine, are the mechanisms underlying the LDR. Conversely, experience-dependent aberrant plasticity that develops slowly under reduced dopamine levels could contribute substantially to PD motor symptoms before initiation of dopamine replacement therapy. We place these findings in the context of the role of dopamine in basal ganglia function and corticostriatal plasticity, and provide a new framework suggesting that therapies that enhance the LDR could be more effective than those targeting the SDR. We further propose that changes in neuroplasticity constitute a form of disease modification that is distinct from prevention of degeneration, and could be responsible for some of the unexplained disease-modifying effects of certain therapies. Understanding such plasticity could provide novel therapeutic approaches that combine rehabilitation and pharmacotherapy for treatment of neurological and psychiatric disorders involving basal ganglia dysfunction.
AB - Dopamine replacement is a mainstay of therapeutic strategies for Parkinson disease (PD). The motor response to therapy involves an immediate improvement in motor function, known as the short-duration response (SDR), followed by a long-duration response (LDR) that develops more slowly, over weeks. Here, we review evidence in patients and animal models suggesting that dopamine-dependent corticostriatal plasticity, and retention of such plasticity in the absence of dopamine, are the mechanisms underlying the LDR. Conversely, experience-dependent aberrant plasticity that develops slowly under reduced dopamine levels could contribute substantially to PD motor symptoms before initiation of dopamine replacement therapy. We place these findings in the context of the role of dopamine in basal ganglia function and corticostriatal plasticity, and provide a new framework suggesting that therapies that enhance the LDR could be more effective than those targeting the SDR. We further propose that changes in neuroplasticity constitute a form of disease modification that is distinct from prevention of degeneration, and could be responsible for some of the unexplained disease-modifying effects of certain therapies. Understanding such plasticity could provide novel therapeutic approaches that combine rehabilitation and pharmacotherapy for treatment of neurological and psychiatric disorders involving basal ganglia dysfunction.
UR - http://www.scopus.com/inward/record.url?scp=84877575193&partnerID=8YFLogxK
U2 - 10.1038/nrneurol.2013.57
DO - 10.1038/nrneurol.2013.57
M3 - Review article
C2 - 23588357
AN - SCOPUS:84877575193
SN - 1759-4758
VL - 9
SP - 248
EP - 256
JO - Nature Reviews Neurology
JF - Nature Reviews Neurology
IS - 5
ER -