Abstract
The striatum, a major component of the basal ganglia, performs multiple functions including control of movement, reward, and addiction. Dysfunction and death of striatal neurons are the main causes for the motor disorders associated with Huntington’s disease (HD). Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is among factors that promote survival and proper function of this neuronal population. Here, we review recent studies showing that BDNF determines the size of the striatum by supporting survival of the immature striatal neurons at their origin, promotes maturation of striatal neurons, and facilitates establishment of striatal connections during brain development. We also examine the role of BDNF in maintaining proper function of the striatum during adulthood, summarize the mechanisms that lead to a deficiency in BDNF signaling and subsequently striatal degeneration in HD, and highlight a potential role of BDNF as a therapeutic target for HD treatment.
Highlights
The striatum is the largest component of the basal ganglia
Direct pathway neurons that express dopamine receptor D1a (DRD1a) are less affected, and striatal interneurons are mostly spared in patients with Huntington’s disease (HD) (Ferrante et al, 1987a,b). In agreement with these facts, only 18% of DRD1a medium-sized spiny neurons (MSNs) express TrkB at P10 (Figure 1E, Baydyuk et al, 2011). These findings indicate that decreased Brain-derived neurotrophic factor (BDNF)-TrkB signaling may preferentially affect indirect pathway MSNs, which express most of the TrkB in the striatum, explaining the selective degeneration of this population and motor phenotype seen in HD
We show that the Bdnf transgene is able to greatly increase BDNF levels in the striata of two HD mouse lines, R6/1 and YAC128, indicating that BDNF overexpressed in the cortex is efficiently transported to the striatum, despite the presence of mutant htt
Summary
Dysfunction and death of striatal neurons are the main causes for the motor disorders associated with Huntington’s disease (HD). Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is among factors that promote survival and proper function of this neuronal population. We review recent studies showing that BDNF determines the size of the striatum by supporting survival of the immature striatal neurons at their origin, promotes maturation of striatal neurons, and facilitates establishment of striatal connections during brain development. We examine the role of BDNF in maintaining proper function of the striatum during adulthood, summarize the mechanisms that lead to a deficiency in BDNF signaling and subsequently striatal degeneration in HD, and highlight a potential role of BDNF as a therapeutic target for HD treatment
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