An intrastriatal brain-derived neurotrophic factor infusion restores striatal gene expression in Bdnf heterozygous mice

Reduction in the amount of brain-derived neurotrophic factor (BDNF) in corticostriatal afferents is thought to contribute to the vulnerability of medium spiny striatal neurons in Huntington’s disease. In young Bdnf heterozygous (+/−) mice, striatal medium spiny neurons (MSNs) express less preprodynorphin (PPD), preproenkephalin (PPE), and D3 receptor mRNA than wildtype mice. Further, in aged Bdnf+/− mice, opioid, trkB receptor, and glutamic acid decarboxylase gene expression, and the number of dendritic spines on MSNs are more affected than in wildtype or younger Bdnf+/− mice. In this study, the possibility that intrastriatal infusions of BDNF would elevate gene expression in the striatum of Bdnf+/− mice was investigated. Wildtype and Bdnf+/− mice received a single, bilateral microinjection of BDNF or PBS into the dorsal striatum. Mice were killed 24 h later and semi-quantitative in situ hybridization histochemical analysis confirmed that PPD, PPE, and D3 receptor mRNA was less in the caudate-putamen (CPu) and nucleus accumbens (NAc) core of Bdnf+/− mice than in wildtype mice. A BDNF infusion increased PPD mRNA in the CPu and NAc core of wildtype mice and restored PPD mRNA levels in the NAc core of Bdnf+/− mice. BDNF also restored the gene expression of PPE in the CPu of Bdnf+/− mice to wildtype levels; however, PPE mRNA in the NAc did not differ among groups. Furthermore, BDNF increased D3 receptor mRNA in the NAc core of wildtype and Bdnf+/− mice. These results demonstrate that exogenous BDNF restores striatal opioid and D3R gene expression in mice with genetically reduced levels of endogenous BDNF.