Croll S D, Wiegand S J, Anderson K D, Lindsay R M, Nawa H
Regeneron Pharmaceuticals, Tarrytown, NY 10591.
Eur J Neurosci. 1994 Aug 1;6(8):1343-53. doi: 10.1111/j.1460-9568.1994.tb00325.x.
The expression of neuropeptides and neurotrophic factors is altered in the hippocampus after seizure induction in rats. Because the increase in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) mRNAs precede changes in neuropeptide expression after seizure, it is possible that BDNF and NGF mediate subsequent alterations in peptide expression. To test this hypothesis directly, BDNF or NGF was infused into the hippocampus and cortex of adult rats. To ascertain the regional specificity of any observed effects of neurotrophin administration on neuropeptide expression, infusions into the striatum were also studied. To control for specificity, vehicle was also infused into the same sites. Peptide and mRNA alterations were assessed by Northern analysis, immunohistochemistry and radioimmunoassay. BDNF produced elevations of peptide and mRNA for neuropeptide Y and cholecystokinin in hippocampus and cortex, and somatostatin in cortex. BDNF increased mRNAs for neuropeptide Y, cholecystokinin, substance P and dynorphin in striatum. In contrast, BDNF decreased dynorphin peptide and mRNA in hippocampus. NGF's effects were limited to small mRNA increases, without corresponding changes in peptide levels, for neuropeptide Y in hippocampus and striatum, substance P in cortex and cholecystokinin in striatum. The distinct and limited effects of NGF infusion on neuropeptide expression demonstrate that BDNF's effects are not non-specific results of protein infusion into the brain. These findings indicate that BDNF may play a regionally specific role in modulating neuropeptide expression in the normal brain as well as in various pathophysiological states.
在大鼠诱发癫痫后，海马体中神经肽和神经营养因子的表达会发生改变。由于癫痫发作后，脑源性神经营养因子（BDNF）和神经生长因子（NGF）mRNA的增加先于神经肽表达的变化，因此BDNF和NGF有可能介导了随后肽表达的改变。为了直接验证这一假设，将BDNF或NGF注入成年大鼠的海马体和皮质。为了确定神经营养素给药对神经肽表达的任何观察到的影响的区域特异性，还研究了注入纹状体的情况。为了控制特异性，也将溶剂注入相同部位。通过Northern分析、免疫组织化学和放射免疫测定来评估肽和mRNA的变化。BDNF使海马体和皮质中神经肽Y和胆囊收缩素的肽和mRNA升高，使皮质中生长抑素升高。BDNF使纹状体中神经肽Y、胆囊收缩素、P物质和强啡肽的mRNA增加。相比之下，BDNF使海马体中强啡肽肽和mRNA减少。NGF的作用仅限于海马体和纹状体中神经肽Y、皮质中P物质以及纹状体中胆囊收缩素的mRNA小幅增加，而肽水平没有相应变化。NGF注入对神经肽表达的独特而有限的影响表明，BDNF的作用并非是向脑内注入蛋白质的非特异性结果。这些发现表明，BDNF可能在调节正常大脑以及各种病理生理状态下的神经肽表达中发挥区域特异性作用。
