Unsain Nicolás, Montroull Laura Ester, Mascó Daniel Hugo
Facultad de Ciencias Exactas, Físicas y Naturales, Laboratorio de Neurobiología, Centro de Biología Celular y Molecular, Cátedra de Biología Celular, Universidad Nacional de Córdoba, Córdoba, Argentina.
J Neurochem. 2009 Oct;111(2):428-40. doi: 10.1111/j.1471-4159.2009.06342.x. Epub 2009 Aug 17.
Brain-derived neurotrophic factor (BDNF) is involved in many aspects of neuronal biology and hippocampal physiology. Status epilepticus (SE) is a condition in which prolonged seizures lead to neuronal degeneration. SE-induced in rodents serves as a model of Temporal Lobe Epilepsy with hippocampal sclerosis, the most frequent epilepsy in humans. We have recently described a strong correlation between TrkB decrease and p75ntr increase with neuronal degeneration (Neuroscience 154:978, 2008). In this report, we report that local, acute intra-hippocampal infusion of function-blocking antibodies against BDNF prevented both early TrkB down-regulation and neuronal degeneration after SE. Conversely, the infusion of recombinant human BDNF protein after SE greatly increased neuronal degeneration. The inhibition of BDNF mRNA translation by the infusion of antisense oligonucleotides induced a rapid decrease of BDNF protein levels, and a delayed increase. If seizures were induced at the time endogenous BDNF was decreased, SE-induced neuronal damage was prevented. On the other hand, if seizures were induced at the time endogenous BDNF was increased, SE-induced neuronal damage was exacerbated. These results indicate that under a pathological condition BDNF exacerbates neuronal injury.
脑源性神经营养因子（BDNF）参与神经元生物学和海马生理学的多个方面。癫痫持续状态（SE）是一种长时间癫痫发作导致神经元变性的病症。在啮齿动物中诱导的SE可作为伴有海马硬化的颞叶癫痫模型，这是人类最常见的癫痫类型。我们最近描述了TrkB减少与p75ntr增加与神经元变性之间存在强烈相关性（《神经科学》154:978，2008年）。在本报告中，我们报道局部、急性海马内注射抗BDNF功能阻断抗体可预防SE后早期TrkB下调和神经元变性。相反，SE后注射重组人BDNF蛋白会大大增加神经元变性。通过注射反义寡核苷酸抑制BDNF mRNA翻译会导致BDNF蛋白水平迅速下降，并延迟升高。如果在内源性BDNF减少时诱发癫痫发作，则可预防SE诱导的神经元损伤。另一方面，如果在内源性BDNF增加时诱发癫痫发作，则SE诱导的神经元损伤会加剧。这些结果表明，在病理条件下BDNF会加剧神经元损伤。
