Wolf Daniel, Ayon-Olivas Maurilyn, Sendtner Michael
Institute of Clinical Neurobiology, University Hospital Wuerzburg, 97078 Wuerzburg, Germany.
Biomedicines. 2024 Aug 5;12(8):1761. doi: 10.3390/biomedicines12081761.
Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), act as key regulators of neuronal development, survival, and plasticity. BDNF is necessary for neuronal and functional maintenance in the striatum and the substantia nigra, both structures involved in the pathogenesis of Parkinson's Disease (PD). Depletion of BDNF leads to striatal degeneration and defects in the dendritic arborization of striatal neurons. Activation of tropomyosin receptor kinase B (TrkB) by BDNF is necessary for the induction of long-term potentiation (LTP), a form of synaptic plasticity, in the hippocampus and striatum. PD is characterized by the degeneration of nigrostriatal neurons and altered striatal plasticity has been implicated in the pathophysiology of PD motor symptoms, leading to imbalances in the basal ganglia motor pathways. Given its essential role in promoting neuronal survival and meditating synaptic plasticity in the motor system, BDNF might have an important impact on the pathophysiology of neurodegenerative diseases, such as PD. In this review, we focus on the role of BDNF in corticostriatal plasticity in movement disorders, including PD and dystonia. We discuss the mechanisms of how dopaminergic input modulates BDNF/TrkB signaling at corticostriatal synapses and the involvement of these mechanisms in neuronal function and synaptic plasticity. Evidence for alterations of BDNF and TrkB in PD patients and animal models are reviewed, and the potential of BDNF to act as a therapeutic agent is highlighted. Advancing our understanding of these mechanisms could pave the way toward innovative therapeutic strategies aiming at restoring neuroplasticity and enhancing motor function in these diseases.
神经营养因子，特别是脑源性神经营养因子（BDNF），是神经元发育、存活和可塑性的关键调节因子。BDNF对于纹状体和黑质中的神经元及功能维持是必需的，这两个结构都参与帕金森病（PD）的发病机制。BDNF的缺失会导致纹状体退化以及纹状体神经元树突分支的缺陷。BDNF对原肌球蛋白受体激酶B（TrkB）的激活，对于海马体和纹状体中长时程增强（LTP，一种突触可塑性形式）的诱导是必需的。PD的特征是黑质纹状体神经元退化，纹状体可塑性改变与PD运动症状的病理生理学有关，导致基底神经节运动通路失衡。鉴于BDNF在促进神经元存活和调节运动系统突触可塑性方面的重要作用，它可能对包括PD在内的神经退行性疾病的病理生理学产生重要影响。在本综述中，我们聚焦于BDNF在运动障碍（包括PD和肌张力障碍）的皮质纹状体可塑性中的作用。我们讨论了多巴胺能输入如何在皮质纹状体突触处调节BDNF/TrkB信号传导的机制，以及这些机制在神经元功能和突触可塑性中的作用。综述了PD患者和动物模型中BDNF和TrkB改变的证据，并强调了BDNF作为治疗剂的潜力。深入了解这些机制可能为旨在恢复神经可塑性和增强这些疾病运动功能的创新治疗策略铺平道路。
