Hypothalamic Compensatory Mechanisms in Parkinson's Disease

Abstract

Parkinson's disease (PD) is associated with loss of dopaminergic neurons of the nigrostriatal bundle and to a lesser extent of the mesolimbic and hypothalamic dopaminergic systems. Frank symptoms of the disease usually emerge when at least 70-80% of striatal dopamine (DA) content have been reduced, raising the possibility that the preclinical phase of the disease might be due to compensatory changes that permit residual dopaminergic neurons to subserve functions previously carried out by the entire projection. These neurochemical compensatory mechanisms are known to occur at a striatal level of the rate limiting enzymes of catecholamine synthesis as well as alterations in the sensitivity of the dopaminergic postsynaptic receptors (Zigmond et al., 1984; Bokobza et al., 1984). Compensatory mechanisms, although generally less well recognized, also occur in the hypothalamus and involve endocrine regulation, abnormal neuropeptide release and the emergence of several autonomic and sensory symptoms manifesting prior to or during the course of the disease. Such neurochemical and clinical adaptation mechanisms of the hypothalamus may help to explain the neurobiological events underlying the preclinical phase of Parkinsonism. Moreover, progressive failure of these hypothalamic adaptive mechanisms may be critical in the transition of the disease into the “malignant phase” (Danielczyk et al., 1980).

Key Words:

• parkinson's disease
• hypothalamus
• dopamine
• POMC-peptides