Medical Sciences Graduate Program, Faculty of Health Sciences, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
Department of Psychiatry and Behavioral Neurosciences, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada.
Int J Mol Sci. 2022 Jun 20;23(12):6853. doi: 10.3390/ijms23126853.
Nurr1 and brain-derived neurotrophic factor (BDNF) play major roles in cognition. Nurr1 regulates BDNF in midbrain dopaminergic neurons and cerebellar granule cells. Nurr1 and BDNF are also highly expressed in the cerebral cortex, a brain area important in cognition. Due to Nurr1 and BDNF tissue specificity, the regulatory effect of Nurr1 on BDNF in different brain areas cannot be generalized. The relationship between Nurr1 and BDNF in the cortex has not been investigated previously. Therefore, we examined Nurr1-mediated BDNF regulation in cortical neurons in activity-dependent and activity-independent states. Mouse primary cortical neurons were treated with the Nurr1 agonist, amodiaquine (AQ). Membrane depolarization was induced by KCl or veratridine and reversed by nimodipine. AQ and membrane depolarization significantly increased Nurr1 (p < 0.001) and BDNF (pAQ < 0.001, pKCl < 0.01) as assessed by real-time qRT-PCR. However, Nurr1 knockdown did not affect BDNF gene expression in resting or depolarized neurons. Accordingly, the positive correlation between Nurr1 and BDNF expression in AQ and membrane depolarization experiments does not imply co-regulation because Nurr1 knockdown did not affect BDNF gene expression in resting or depolarized cortical neurons. Therefore, in contrast to midbrain dopaminergic neurons and cerebellar granule cells, Nurr1 does not regulate BDNF in cortical neurons.
Nurr1 和脑源性神经营养因子 (BDNF) 在认知中发挥重要作用。Nurr1 调节中脑多巴胺能神经元和小脑颗粒细胞中的 BDNF。Nurr1 和 BDNF 在大脑皮层中也高度表达，大脑皮层是认知的重要区域。由于 Nurr1 和 BDNF 的组织特异性，Nurr1 对不同脑区 BDNF 的调节作用不能一概而论。以前没有研究过 Nurr1 和 BDNF 之间在皮质中的关系。因此，我们研究了在依赖于活动和不依赖于活动的状态下，Nurr1 对皮质神经元中 BDNF 的调节作用。用 Nurr1 激动剂阿莫地喹 (AQ) 处理原代培养的小鼠皮质神经元。用 KCl 或藜芦碱诱导膜去极化，并用尼莫地平逆转。实时 qRT-PCR 结果显示，AQ 和膜去极化显著增加了 Nurr1（p < 0.001）和 BDNF（pAQ < 0.001，pKCl < 0.01）。然而，Nurr1 敲低并不影响静息或去极化神经元中 BDNF 基因的表达。因此，在 AQ 和膜去极化实验中 Nurr1 和 BDNF 表达之间的正相关并不意味着共同调节，因为 Nurr1 敲低并不影响静息或去极化皮质神经元中 BDNF 基因的表达。因此，与中脑多巴胺能神经元和小脑颗粒细胞不同，Nurr1 不调节皮质神经元中的 BDNF。
