Scholarlink

<p>Parkinson’s disease (PD) is a neurodegenerative disorder marked by loss of substantia nigra dopaminergic neurons. Epidemiological evidence indicates that lifelong physical activity reduces both PD incidence and slows disease progression. Here, we examine how voluntary exercise induces long-lasting neuroprotection of the corticostriatal function in a murine model of α-synuclein–driven nigrostriatal pathology. In preformed fibril (PFF)-injected mice, long-lasting voluntary wheel running prevents degeneration of nigrostriatal dopaminergic terminals and improves motor performances. Intensive exercise normalizes spontaneous glutamatergic transmission and preserves corticostriatal long-term potentiation (LTP) in striatal spiny projection neurons. Exercise-induced LTP is dependent on activation of dopamine (DA) DA1, GluN2B-expressing NMDA and CB1 endocannabinoid (eCB) receptors. Pharmacological modulation of exercise-induced plasticity shows that, while in physiological conditions eCBs regulate synaptic depotentiation, persistence of LTP in active α-syn mice occurs independently of the eCB system, highlighting a critical interaction between DA and eCBs in long-term synaptic regulation. These findings identify voluntary exercise as a robust neuroprotective intervention with therapeutic relevance for early PD.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dopamine–endocannabinoid crosstalk drives exercise-induced bidirectional plasticity in Parkinson’s disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月1日

查看全文
  • Federica Campanelli,
  • Gioia Marino,
  • Giuseppina Natale,
  • Maria De Carluccio,
  • Tabitha N. Rodriguez,
  • Michelle Smeyne,
  • Richard Jay Smeyne,
  • Veronica Ghiglieri,
  • Paolo Calabresi

摘要

Parkinson’s disease (PD) is a neurodegenerative disorder marked by loss of substantia nigra dopaminergic neurons. Epidemiological evidence indicates that lifelong physical activity reduces both PD incidence and slows disease progression. Here, we examine how voluntary exercise induces long-lasting neuroprotection of the corticostriatal function in a murine model of α-synuclein–driven nigrostriatal pathology. In preformed fibril (PFF)-injected mice, long-lasting voluntary wheel running prevents degeneration of nigrostriatal dopaminergic terminals and improves motor performances. Intensive exercise normalizes spontaneous glutamatergic transmission and preserves corticostriatal long-term potentiation (LTP) in striatal spiny projection neurons. Exercise-induced LTP is dependent on activation of dopamine (DA) DA1, GluN2B-expressing NMDA and CB1 endocannabinoid (eCB) receptors. Pharmacological modulation of exercise-induced plasticity shows that, while in physiological conditions eCBs regulate synaptic depotentiation, persistence of LTP in active α-syn mice occurs independently of the eCB system, highlighting a critical interaction between DA and eCBs in long-term synaptic regulation. These findings identify voluntary exercise as a robust neuroprotective intervention with therapeutic relevance for early PD.