BDNF sensitizes the response of lamina II neurons to high threshold primary afferent inputs
BDNF sensitizes the response of lamina II neurons to high threshold primary afferent inputs
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DOI：
10.1046/j.1460-9568.2003.02982.x
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发表时间：
2003-11-01
影响因子：
3.4
通讯作者：
Mendell, LM
中科院分区：
文献类型：
--
作者：
Garraway, SM;Petruska, JC;Mendell, LM
外周炎症后，脑源性神经营养因子（BDNF）在背角上调并释放，因此与脊髓致敏机制有关。尽管有这些观察结果，与BDNF的这种作用相关的机制尚未完全确定。在此，我们研究了BDNF对II层神经元背根诱发突触传递的影响。在新生大鼠（P1-15）的横断脊髓切片制备中，采用全细胞膜片钳技术记录这些神经元。短暂应用BDNF （50 ~ 200 ng/mL）可促进突触电流的诱发；即使在BDNF被清除后，它们仍保持增强。相当一部分细胞受BDNF的影响最小，与此一致的是，并非II层的所有神经元对酪氨酸激酶（trk） B受体都有免疫反应。当用D-APV阻断n -甲基- d -天冬氨酸（NMDA）受体、细胞内MK-801选择性阻断突触后NMDA受体或突触后神经元负载BAPTA时，均未引起促进作用。此外，在BDNF应用之前，抑制磷脂酶C （PLC）或蛋白激酶C （PKC）完全阻断了促进作用。然而，一旦突触电流发生bdnf诱导的促进作用，PKC抑制剂就无法逆转这一作用，这表明启动bdnf诱导的促进作用需要PKC，而不是维持。这些结果表明，BDNF在脊髓水平上以NMDA受体依赖的方式增强突触效能，并需要PLC/PKC通路的作用。BDNF的这种作用可能导致中枢致敏和疼痛状态的夸大。
Brain-derived neurotrophic factor (BDNF) is up-regulated and released in the dorsal horn following peripheral inflammation and has therefore been implicated in spinal mechanisms of sensitization. Despite these observations, the mechanisms associated with such a role for BDNF are not yet fully determined. Here, we investigate the effect of BDNF on dorsal root-evoked synaptic transmission in lamina II neurons. In a transverse spinal cord slice preparation from neonatal rats (P1-15), the whole cell patch-clamp technique was used to record from these neurons. Brief application of BDNF (50-200 ng/mL) facilitated the evoked synaptic currents; they remained enhanced even after BDNF was washed out. A significant minority of cells was minimally affected by BDNF and consistent with this, not all neurons in lamina II were immunoreactive for the tyrosine kinase (trk) B receptor. No facilitation was elicited when N-methyl-D-aspartate (NMDA) receptors were blocked with D-APV, when the postsynaptic NMDA receptors were selectively blocked with intracellular MK-801, or when postsynaptic neurons were loaded with BAPTA. Additionally, inhibiting phospholipase C (PLC) or protein kinase C (PKC) prior to BDNF application completely blocked facilitation. However, once synaptic current underwent BDNF-induced facilitation, the PKC inhibitors failed to reverse the effect, suggesting that PKC is needed for initiation, but not maintenance of BDNF-induced facilitation. These results demonstrate that BDNF functions at the spinal level to enhance synaptic efficacy in an NMDA receptor-dependent manner and requires the action of the PLC/PKC pathway. This action of BDNF may contribute to central sensitization and exaggerated pain states.