Reduced expression of preproenkephalin in striatal neurons from huntington's disease patients

Eric K. Richfield, Kathleen A. Maguire‐Zeiss, Christopher Cox, Jennifer Gilmore, Pieter Voorn

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69 Scopus citations


Differential loss of neurons and terminals occurs in Huntington's disease. Neurons expressing preproenkephalin (PPE) appear to be more vulnerable than neurons expressing preprotachykinin and terminals in the lateral pallidum (containing enkephalin) are more affected than terminals in the medial pallidum (containing substance P). We used in situhybridization histochemistry and emulsion autoradiography to quantify the number of PPE expressing neurons and the neuronal levels of PPE mRNA in striatum of individuals who died with Huntington's disease and normal controls. We found a grade‐related decline in the number of PPE‐labeled neurons per field in the striatum of individuals with Huntington's disease compared with controls. Three measures of the neuronal level of PPE mRNA, the mean number of silver grains per PPE neuron, the median number of grains per PPE neuron, and the percentage of PPE neurons with more than 30 grains, were all significantly reduced (41 to 80% of control) in Huntington's disease striatum. The magnitude of the reduction in levels of PPE mRNA per neuron was related to the grade of lesions. These data support the notion that decreased levels of PPE mRNA may account, in part, for the greater loss of enkephalin staining in lateral pallidal terminals compared with substance P staining in medial pallidal terminals. Decreased levels of PPE mRNA may result in clinical symptoms prior to the loss of neurons. The reduction in expression of PPE mRNA suggests that surviving striatal neurons may be affected by the expression of the Huntington's disease gene prior to their imminent cell death.

Original languageEnglish (US)
Pages (from-to)335-343
Number of pages9
JournalAnnals of neurology
Issue number3
StatePublished - Mar 1995
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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