Changing views of the pathophysiology of Parkinsonism

Abstract

Studies of the pathophysiology of parkinsonism (specifically akinesia and bradykinesia) have a long history and primarily model the consequences of dopamine loss in the basal ganglia on the function of the basal ganglia/thalamocortical circuit(s). Changes of firing rates of individual nodes within these circuits were originally considered central to parkinsonism. However, this view has now given way to the belief that changes in firing patterns within the basal ganglia and related nuclei are more important, including the emergence of burst discharges, greater synchrony of firing between neighboring neurons, oscillatory activity patterns, and the excessive coupling of oscillatory activities at different frequencies. Primarily focusing on studies obtained in nonhuman primates and human patients with Parkinson's disease, this review summarizes the current state of this field and highlights several emerging areas of research, including studies of the impact of the heterogeneity of external pallidal neurons on parkinsonism, the importance of extrastriatal dopamine loss, parkinsonism‐associated synaptic and morphologic plasticity, and the potential role(s) of the cerebellum and brainstem in the motor dysfunction of Parkinson's disease. © 2019 International Parkinson and Movement Disorder Society

Behavioral, Biochemical and Histopathological effects of Standardised Pomegranate extract with Vinpocetine, Propolis or Cocoa in a rat model of Parkinson’s disease

“…Increased generation of ROS leads to elevation of the lipid peroxidation level yielding malondialdehyde (MDA) which can be considered as a biomarker for oxidative stress. Also, other factors observed in Parkinsonism pathology are glutathione (GSH) depletion, enhanced superoxide activity, and cellular apoptosis [11,12].…”

Starting from Scratch—Basal Ganglia Pathophysiology

“…Wichmann reviewed accumulated facts and many theories regarding basal ganglia pathophysiology. Theory is the lifeblood of science.…”

“…How is it some patients with Huntington's disease have bradykinesia as well? If increased synchrony is causal to PD, how is it that therapeutic deep brain stimulation (DBS) drives synchrony, demonstrated by DBS‐evoked potentials in the electroencephalogram? If increased beta oscillations cause PD, how is it that some patients with PD and parkinsonian primates do not show increased low‐frequency power, and why does bradykinesia improve with DBS at these frequencies? There are many counterexamples …”

“…As Wichmann alluded, the central question in constructing theories regards causality. The ultimate “cause” of disorders of movements are abnormalities is the orchestration of motor unit activity at multiple levels and time frames; it could not be otherwise.…”

“…), agonist and antagonist cocontraction at force onset, abnormal scaling of the triphasic response, and breakdown of synergies among motor unit recruitments across multiple muscles in complex movements, among others . It is not at all clear how any of the theories enumerated by Wichmann and others would explain these findings. No theory should be considered plausible unless it is predicated on the pathophysiology of motor unit recruitment.…”