title: Modeling Parkinson's disease falls associated with brainstem cholinergic systems decline.
abstract: 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.
authors: Department of Psychology, University of Michigan.
authors: Aaron
authors: A
authors: Kucinski
authors: Department of Psychology, University of Michigan.
authors: Martin
authors: M
authors: Sarter
mesh_terms: D000058:Accidental Falls; D000818:Animals; D066187:Basal Forebrain / Q000503:physiopathology; D002421:Caudate Nucleus / Q000503:physiopathology; D059329:Cholinergic Neurons / Q000502:physiology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D005684:Gait; D008297:Male; D010300:Parkinson Disease / Q000150:complications / Q000503:physiopathology*; D045042:Pedunculopontine Tegmental Nucleus / Q000503:physiopathology*; D004856:Postural Balance; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004298:Dopamine