The brain’s own mechanisms for dealing with the loss of dopamine neurons in Parkinson’s disease may be a source of the disorder’s abnormal movement, according to a study published in Neuron.

The study suggests the loss of dopamine may cause the brain to rewire in a maladaptive manner, contributing to impaired movement in Parkinson’s disease. These findings also suggest that there are fundamental problems with scientists’ traditional model of Parkinson’s disease, according to the researchers.

The prevailing consensus was that excessive patterning of the subthalamic nucleus (STN), a component of the basal ganglia, by the cerebral cortex was linked to the symptomatic expression of Parkinson’s disease, including muscle rigidity and slowness of movement.

Thus, the researchers expected to see transmission in the cortex-to-STN pathway increase as dopamine levels dropped. Instead, they found the opposite: the strength of the pathway decreased massively.

Further investigation suggested abnormal activity in a more indirect pathway from the cortex to the STN, involving the globus pallidus, was responsible. Abnormal activity in the indirect pathway leaves the STN vulnerable to excessive excitation, triggering compensatory plasticity that ultimately proved to be harmful, according to the study.

When the scientists prevented this maladaptive plasticity in late-stage Parkinson’s models, they found the symptoms improved, pointing to a link between compensation and motor dysfunction.

While the compensatory mechanisms may initially keep the brain operating normally under conditions of moderate dopamine neuron loss, as the disease progresses and more dopamine neurons die, the adaptations may become so extreme that they impair movement, according to the study.

These results suggest that there are fundamental flaws in our traditional understanding of brain dysfunction in Parkinson’s disease.

Paper: “Loss of Hyperdirect Pathway Cortico-Subthalamic Inputs Following Degeneration of Midbrain Dopamine Neurons”
Reprinted from materials provided by Northwestern University.

ינואר 26, 2018