How does Thalamic Damage Contribute to Parkinsonism? Implications for Treatment

Dr Jasmine Henderson, Department of Pharmacology, University of Sydney

Parkinson’s disease (PD) is characterised clinically by the presence of symptoms such as slow movements, muscular rigidity, tremor and postural abnormalities. Pathologically there is loss of cells producing a chemical transmitter substance called dopamine from a region of the midbrain called the substantia nigra.

My colleagues and I have discovered degeneration within a different brain region called the thalamus in patients with PD.^1,2 The degeneration is quite selective and only occurs in a part of the thalamus called the centromedian-parafascicular complex (CM-Pf). This important discovery has raised new and yet unanswered questions concerning the significance and the type of symptoms that may result from thalamic degeneration in PD.

Such questions are best investigated using animal models of PD. Until now most of the major symptoms of PD were attributed to the deficiency of dopamine in the brain. So far we have found in a pilot study generously funded by the Brain Foundation that thalamic degeneration (induced by lesioning the CM-Pf with a toxin) contributes to postural abnormalities in a rat model of PD.

Our data suggests that thalamic degeneration also contributes to postural instability commonly observed in PD patients. Current drug treatment for PD focuses on replacing the neurotransmitter substance, dopamine. However the affected thalamic neurons do not contain dopamine, but glutamate, an excitatory neurotransmitter substance. Our new data suggests that whilst modest postural instability in PD can arise from dopamine loss alone, additional degeneration of the CM-Pf elicits even more severe postural changes, indicative of an additive effect.

Our data may help explain why severe postural abnormalities in PD are not particularly responsive to dopamine replacement therapy. This is because this strategy does not address the deficiency in glutamate occurring as a result of degeneration of the thalamus in PD. Based on these observations we are now planning a larger scale study in which we will compare drugs that affect the midbrain (dopamine) and thalamic (glutamate) systems for their effects on parkinsonian symptoms using the same animal model. This approach could ultimately lead to the development of better treatments for patients with PD.

¹Henderson JM, Carpenter K, Cartwright H, Halliday GM. Degeneration of the centre median-parafascicular complex in Parkinson’s disease. Annals of Neurology 2000;47:345-352.

²Henderson JM, Carpenter K, Cartwright H, Halliday GM. Loss of thalamic intralaminar thalamus in progressive supranuclear palsy and Parkinson’s disease: clinical and therapeutic implications. Brain 2000; 123:1410-1421.