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The hypothalamus in MPTP-induced parkinsonism

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Abstract

1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) has been shown to produce a parkinsonian syndrome in humans and other primates. Recent studies have demonstrated that in humans the hypothalamus has the highest binding density for (3H) MPTP, which corresponds to monoamine oxidase type B (MAO-B). There is evidence that the conversion of MPTP to the toxic compound MPP+ takes place in the hypothalamus; subsequently, MPP+ is transported to the striatal system, where destruction of nigrostriatal dopamine neurons occurs. Thus, the hypothalamus appears to be a primary target organ of MPTP toxicity. This assumption is supported by the observation that monkeys exposed to MPTP exhibit extensive pathological lesions in the hypothalamus which are manifested clinically by the development of life-threatening anorexia requiring forced feeding to overcome. We discuss the clinical implications of MPTP-induced hypothalamic damage to the pathophysiology of MPTP-induced parkinsonism and to Parkinson disease. It is suggested that consideration of hypothalamic involvement in MPTP-induced parkinsonism may provide a broader understanding of the pathophysiology of parkinsonism and may, in addition, account for the preliminary observations that MAO-B inhibitors retard the progression of Parkinson disease and possibly prolong life expectancy.

Sommario

La l-metil-4-fenil-1,2,5,6 tetraidropiridina (MPTP) produce una sindrome parkinsoniana nell'uomo e in alcuni primati; studi recenti hanno dimostrato che nell'uomo l'ipotalamo ha la più alta capacità di legare il (3H) MPTP. È dimostrato che la conversione dell'MPTP nel composto tossico MPP+ si svolge nell'ipotalamo; successivamente lo MPP+ è trasportato al sistema striato e quindi si determina una distribuzione dei neuroni della dopamina nigrostriatale. Risulta così che l'ipotalamo è l'organo bersaglio primario della tossicità dell'MPTP e ciò è dimostrato dalla osservazione che le scimmie esposte al-l'azione dell'MPTP presentano estese lesioni patologiche nell'ipotalamo e manifestano clinicamente una anoressia di tale gravità da richiedere l'alimentazione forzata. Noi discutiamo le implicazioni cliniche del danno ipotalamico da MPTP con la patofisiologia del parkinsonismo indotto da MPTP e col morbo di Parkinson. Riteniamo che l'interessamento ipotalamico nel Parkinson indotto da MPTP può dare una più ampia interpretazione della fisiopatofisiologia del parkinsonismo e può dare spiegazione di osservazioni preliminari che dimostrano che i MAO-B inibitori ritardano la progressione del morbo di Parkinson e prolungano probabilmente l'aspettativa di vita.

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Authors and Affiliations

  1. Department of Psychiatry, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York, U.S.A.

    Sandyk R. M.D. & Kay S. R.

  2. Department of Surgery (Neurosurgery), University of Arizona Health Sciences Center, Tucson, Arizona, U.S.A.

    Iacono R. P.

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  1. Sandyk R. M.D.
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Sandyk, R., Iacono, R.P. & Kay, S.R. The hypothalamus in MPTP-induced parkinsonism. Ital J Neuro Sci 11, 367–372 (1990). https://doi.org/10.1007/BF02335939

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