Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
Brain Struct Funct. 2010 Aug;215(2):97-104. doi: 10.1007/s00429-010-0282-9. Epub 2010 Oct 12.
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 D(3) 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 D(3) 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 D(3) receptor mRNA in the NAc core of wildtype and Bdnf (+/-) mice. These results demonstrate that exogenous BDNF restores striatal opioid and D(3)R gene expression in mice with genetically reduced levels of endogenous BDNF.
脑源性神经营养因子（BDNF）在皮质纹状体传入纤维中的含量减少被认为是亨廷顿病中型多棘星状神经元易损性的原因。在年轻的 Bdnf 杂合子（+/-）小鼠中，纹状体中型多棘星状神经元（MSNs）表达的前原啡肽（PPD）、前强啡肽（PPE）和 D3 受体 mRNA 少于野生型小鼠。此外，在老年 Bdnf（+/-）小鼠中，阿片类、trkB 受体和谷氨酸脱羧酶基因表达以及 MSNs 树突棘的数量比野生型或年轻的 Bdnf（+/-）小鼠更受影响。在这项研究中，研究了纹状体内 BDNF 输注是否会提高 Bdnf（+/-）小鼠纹状体中的基因表达。野生型和 Bdnf（+/-）小鼠接受单侧、双侧 BDNF 或 PBS 微注射到纹状体背侧。24 小时后处死小鼠，半定量原位杂交组织化学分析证实 Bdnf（+/-）小鼠的尾壳核（CPu）和伏隔核核心（NAc）中的 PPD、PPE 和 D3 受体 mRNA 少于野生型小鼠。BDNF 输注增加了野生型小鼠 CPu 和 NAc 核心中的 PPD mRNA，并恢复了 Bdnf（+/-）小鼠 NAc 核心中的 PPD mRNA 水平。BDNF 还恢复了 Bdnf（+/-）小鼠 CPu 中 PPE 的基因表达至野生型水平；然而，各组之间 NAc 中的 PPE mRNA 没有差异。此外，BDNF 增加了野生型和 Bdnf（+/-）小鼠 NAc 核心中的 D3 受体 mRNA。这些结果表明，外源性 BDNF 恢复了内源性 BDNF 水平降低的小鼠纹状体阿片类和 D3R 基因表达。
