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

Research output: Contribution to journalArticle

Abstract

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 situ hybridization 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
Volume37
Issue number3
DOIs
StatePublished - Mar 1995
Externally publishedYes

Fingerprint

Corpus Striatum
Huntington Disease
Neurons
Messenger RNA
Globus Pallidus
Enkephalins
Substance P
preproenkephalin
Staining and Labeling
Emulsions
Autoradiography
Silver
In Situ Hybridization
Cell Death

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Reduced expression of preproenkephalin in striatal neurons from Huntington's disease patients. / Richfield, Eric K.; Maguire-Zeiss, Kathleen A.; Cox, Christopher; Gilmore, Jennifer; Voorn, Pieter.

In: Annals of Neurology, Vol. 37, No. 3, 03.1995, p. 335-343.

Research output: Contribution to journalArticle

Richfield, Eric K. ; Maguire-Zeiss, Kathleen A. ; Cox, Christopher ; Gilmore, Jennifer ; Voorn, Pieter. / Reduced expression of preproenkephalin in striatal neurons from Huntington's disease patients. In: Annals of Neurology. 1995 ; Vol. 37, No. 3. pp. 335-343.
@article{1c55b31396004c4cb59740d283c37cdd,
title = "Reduced expression of preproenkephalin in striatal neurons from Huntington's disease patients",
abstract = "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 situ hybridization 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.",
author = "Richfield, {Eric K.} and Maguire-Zeiss, {Kathleen A.} and Christopher Cox and Jennifer Gilmore and Pieter Voorn",
year = "1995",
month = "3",
doi = "10.1002/ana.410370309",
language = "English (US)",
volume = "37",
pages = "335--343",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - Reduced expression of preproenkephalin in striatal neurons from Huntington's disease patients

AU - Richfield, Eric K.

AU - Maguire-Zeiss, Kathleen A.

AU - Cox, Christopher

AU - Gilmore, Jennifer

AU - Voorn, Pieter

PY - 1995/3

Y1 - 1995/3

N2 - 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 situ hybridization 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.

AB - 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 situ hybridization 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.

UR - http://www.scopus.com/inward/record.url?scp=0028957560&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028957560&partnerID=8YFLogxK

U2 - 10.1002/ana.410370309

DO - 10.1002/ana.410370309

M3 - Article

C2 - 7695232

AN - SCOPUS:0028957560

VL - 37

SP - 335

EP - 343

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 3

ER -