The pedunculopontine nucleus in Parkinson's disease: primate studies.
Gait freezing and poor balance are two of the most disabling symptoms of advanced Parkinson's disease (PD), and also of other untreatable progressive neurological disorders, such as multi-system atrophy (MSA) and progressive supranuclear palsy (PSP). In PD, these symptoms are currently inadequately managed by drugs and also the present surgical treatment of deep brain stimulation (DBS) of the sub-thalamic nucleus (STN) and the globus pallidus internus (GPi). The pedunculopontine nucleus (PPN) has been implicated in these symptoms. The PPN is in the upper brain stem. The major inhibitory input is from the GPi and substantia nigra reticulata (SNr), and bilateral output is to the substantia nigra compacta (SNc), thalamus and spinal cord. Stimulation of the PPN in the decerebrate rat, cat and dog induced gait-like movements. In autopsy studies in PD, MSA, PSP and the DYT-1 dystonic brain, the PPN is degenerate. Autoradiography of the MPTP-Parkinsonian primate shows excessive inhibition in the PPN. Lesions of the PPN in the normal primate induced PD-type bradykinesia, which was persistent with bilateral lesions. In the MPTP-primate model, microinjections of the gamma aminobutyric acid A (GABA) antagonist bicuculine into the PPN reversed Parkinsonian akinesia implying that stimulation of this region might have a therapeutic role in drug resistant PD. Low frequency (5-10Hz) stimulation of the PPN in the same model reversed akinesia independently of L-dopa; moreover, l-dopa and stimulation effects were additive, implying the involvement of non-dopaminergic pathways.
Nandi
D
D
Imperial College Neuromodulation Group, Charing Cross Hospital and Division of Neuroscience and Mental Health, Imperial College, London, UK.
Jenkinson
N
N
Stein
J
J
Aziz
T
T
D000818:Animals; D046690:Deep Brain Stimulation / Q000379:methods*; D008251:Macaca; D008297:Male; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D045042:Pedunculopontine Tegmental Nucleus / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology