Kucinski Aaron, Sarter Martin
Department of Psychology, University of Michigan.
Behav Neurosci. 2015 Apr;129(2):96-104. doi: 10.1037/bne0000048.
In addition to the primary disease-defining symptoms, approximately half of patients with Parkinson's disease (PD) suffer from postural instability, impairments in gait control and a propensity for falls. Consistent with evidence from patients, we previously demonstrated that combined striatal dopamine (DA) and basal forebrain (BF) cholinergic cell loss causes falls in rats traversing dynamic surfaces. Because evidence suggests that degeneration of brainstem cholinergic neurons arising from the pedunculopontine nucleus (PPN) also contributes to impaired gait and falls, here we assessed the effects of selective cholinergic PPN lesions in combination with striatal DA loss or BF cholinergic cells loss as well as losses in all 3 regions. Results indicate that all combination losses that included the BF cholinergic system slowed traversal and increased slips and falls. However, the performance of rats with losses in all 3 regions (PPN, BF, and DA) was not more severely impaired than following combined BF cholinergic and striatal DA lesions. These results confirm the hypothesis that BF cholinergic-striatal disruption of attentional-motor interactions is a primary source of falls. Additional losses of PPN cholinergic neurons may worsen posture and gait control in situations not captured by the current testing conditions.
除了帕金森病（PD）的主要疾病定义症状外，约一半的帕金森病患者还患有姿势不稳、步态控制障碍和跌倒倾向。与患者的证据一致，我们之前证明纹状体多巴胺（DA）和基底前脑（BF）胆碱能细胞联合缺失会导致大鼠在动态表面行走时跌倒。由于有证据表明，源自脚桥核（PPN）的脑干胆碱能神经元变性也会导致步态受损和跌倒，因此我们在此评估了选择性胆碱能PPN损伤联合纹状体DA缺失或BF胆碱能细胞缺失以及所有三个区域均缺失的影响。结果表明，所有包含BF胆碱能系统的联合缺失都会减缓行走速度，并增加滑倒和跌倒的次数。然而，三个区域（PPN、BF和DA）均缺失的大鼠的表现并不比BF胆碱能和纹状体DA联合损伤后的大鼠更严重受损。这些结果证实了以下假设：BF胆碱能-纹状体对注意力-运动相互作用的破坏是跌倒的主要原因。在当前测试条件未涵盖的情况下，PPN胆碱能神经元的额外缺失可能会使姿势和步态控制恶化。
