Pathophysiology of Parkinson's disease: from clinical neurology to basic neuroscience and back.
Parkinson's disease (PD) is characterized by motor and nonmotor (cognitive and limbic) deficits. The motor signs of PD include hypokinetic signs such as akinesia/bradykinesia, rigidity and loss of normal postural reflexes, and hyperkinetic signs such as tremor. Dopamine depletion in the striatum is the hallmark of PD and of its animal models, still the pathophysiology of the parkinsonian symptoms and especially of parkinsonian tremor are under debate. The most extreme hypotheses argue about peripheral versus central nervous system origin, intrinsic cellular oscillator versus network oscillators, and basal ganglia-based pathophysiology versus cerebellar-thalamic based pathophysiology. Recent studies support the view that parkinsonian symptoms are most likely due to abnormal synchronous oscillating neuronal activity within the basal ganglia. Peripheral factors do only play a minor role for the generation, maintenance, and modulation of PD tremor and other signs. The most likely candidates producing these neuronal oscillations are the weakly coupled neural networks of the basal ganglia-thalamo-cortical loops. However, the present evidence supports the view that the basal ganglia loops are influenced by other neuronal structures and systems and that the tuning of these loops by cerebello-thalamic mechanisms and by other modulator neurotransmitter systems entrain the abnormal synchronized oscillations. Neurosurgical procedures, such as lesions or high-frequency stimulation of different parts of the loop, might resume the normal unsynchronized activity of the basal ganglia circuitry, and, therefore, ameliorate the clinical symptoms of Parkinson's disease.
Bergman
Hagai
H
Department of Physiology and the Eric Roland Center for Neurodegenerative diseases, The Hebrew University, Jerusalem, Israel. hagaib@md.huji.ac.il
Deuschl
Günther
G
D000818:Animals; D001479:Basal Ganglia / Q000503:physiopathology; D004195:Disease Models, Animal; D000882:Haplorhini; D006801:Humans; D020267:MPTP Poisoning / Q000503:physiopathology; D009068:Movement / Q000502:physiology; D009415:Nerve Net / Q000503:physiopathology; D010300:Parkinson Disease / Q000503:physiopathology*; D013788:Thalamus / Q000503:physiopathology; D014202:Tremor / Q000503:physiopathology