PEP-19 immunohistochemistry defines the basal ganglia and associated structures in the adult human brain, and is dramatically reduced in Huntington's disease

A. K. Utal, A. L. Stopka, M. Roy, Paul Coleman

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

We have investigated the distribution of PEP-19, a neuron-specific protein, in the adult human brain. Immunohistochemistry for PEP-19 appears to define the basal ganglia and related structures. The strongest immunoreactivity is seen in the caudate nucleus and putamen, each of which showed both cell body and neuropil PEP-19 immunoreactivity The substantia nigra and both segments of the globus pallidus showed PEP-19 immunoreactivity only in the neuropil. Cell bodies and dendrites of the thalamic nuclei ventralis lateralis and ventralis anterioralis were less strongly immunoreactive. Cerebellar Purkinje cells and their dendrites were immunoreactive, as were the presubiculum/subiculum regions and dentate gyrus granule cells of the hippocampus. The CA zones of the hippocampus were not immunoreactive. Preliminary data from immunoblotting experiments indicate that PEP-19 immunoreactivity is significantly reduced in cerebellum in Alzheimer's disease. While there were no apparent alterations of immunoreactivity in Down's syndrome or in Parkinson's disease, immunohistochemical analysis showed a massive loss of PEP-19 immunoreactivity in the caudate nucleus, putamen, globus pallidus and substantia nigra in Huntington's disease. These results show that PEP-19, a neuron-specific, calmodulin-binding protein, is distributed in specific areas of the adult human brain. The reduction in PEP-19 immunoreactivity in Alzheimer's disease and Huntington's disease suggests that PEP-19 may play a role in the pathophysiology of these diseases through a mechanism of calcium/calmodulin disregulation. This may be especially apparent in Huntington's disease where the distribution of the product of the abnormal gene, huntingtin, alone is not sufficient to explain the pattern of pathology. Abnormal huntingtin associates more strongly with calmodulin than does normal huntingtin [Bao et al. (1996) Proc. natn. Acad Sci. U.S.A., 93. 5037 5042] suggesting a disruption of calmodulin-mediated intracellular mechanism(s), very likely involving PEP-19.

Original languageEnglish (US)
Pages (from-to)1055-1063
Number of pages9
JournalNeuroscience
Volume86
Issue number4
DOIs
StatePublished - Jun 18 1998
Externally publishedYes

Fingerprint

Huntington Disease
Basal Ganglia
Immunohistochemistry
Brain
Calmodulin
Hippocampus
Globus Pallidus
Neuropil
Caudate Nucleus
Putamen
Substantia Nigra
Dendrites
Alzheimer Disease
Peptamen
Calmodulin-Binding Proteins
Ventral Thalamic Nuclei
Neurons
Thalamic Nuclei
Parahippocampal Gyrus
Purkinje Cells

Keywords

  • Alzheimer's disease
  • Basal ganglia
  • Huntington's disease
  • Immunohistochemistry
  • PEP-19

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

PEP-19 immunohistochemistry defines the basal ganglia and associated structures in the adult human brain, and is dramatically reduced in Huntington's disease. / Utal, A. K.; Stopka, A. L.; Roy, M.; Coleman, Paul.

In: Neuroscience, Vol. 86, No. 4, 18.06.1998, p. 1055-1063.

Research output: Contribution to journalArticle

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T1 - PEP-19 immunohistochemistry defines the basal ganglia and associated structures in the adult human brain, and is dramatically reduced in Huntington's disease

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N2 - We have investigated the distribution of PEP-19, a neuron-specific protein, in the adult human brain. Immunohistochemistry for PEP-19 appears to define the basal ganglia and related structures. The strongest immunoreactivity is seen in the caudate nucleus and putamen, each of which showed both cell body and neuropil PEP-19 immunoreactivity The substantia nigra and both segments of the globus pallidus showed PEP-19 immunoreactivity only in the neuropil. Cell bodies and dendrites of the thalamic nuclei ventralis lateralis and ventralis anterioralis were less strongly immunoreactive. Cerebellar Purkinje cells and their dendrites were immunoreactive, as were the presubiculum/subiculum regions and dentate gyrus granule cells of the hippocampus. The CA zones of the hippocampus were not immunoreactive. Preliminary data from immunoblotting experiments indicate that PEP-19 immunoreactivity is significantly reduced in cerebellum in Alzheimer's disease. While there were no apparent alterations of immunoreactivity in Down's syndrome or in Parkinson's disease, immunohistochemical analysis showed a massive loss of PEP-19 immunoreactivity in the caudate nucleus, putamen, globus pallidus and substantia nigra in Huntington's disease. These results show that PEP-19, a neuron-specific, calmodulin-binding protein, is distributed in specific areas of the adult human brain. The reduction in PEP-19 immunoreactivity in Alzheimer's disease and Huntington's disease suggests that PEP-19 may play a role in the pathophysiology of these diseases through a mechanism of calcium/calmodulin disregulation. This may be especially apparent in Huntington's disease where the distribution of the product of the abnormal gene, huntingtin, alone is not sufficient to explain the pattern of pathology. Abnormal huntingtin associates more strongly with calmodulin than does normal huntingtin [Bao et al. (1996) Proc. natn. Acad Sci. U.S.A., 93. 5037 5042] suggesting a disruption of calmodulin-mediated intracellular mechanism(s), very likely involving PEP-19.

AB - We have investigated the distribution of PEP-19, a neuron-specific protein, in the adult human brain. Immunohistochemistry for PEP-19 appears to define the basal ganglia and related structures. The strongest immunoreactivity is seen in the caudate nucleus and putamen, each of which showed both cell body and neuropil PEP-19 immunoreactivity The substantia nigra and both segments of the globus pallidus showed PEP-19 immunoreactivity only in the neuropil. Cell bodies and dendrites of the thalamic nuclei ventralis lateralis and ventralis anterioralis were less strongly immunoreactive. Cerebellar Purkinje cells and their dendrites were immunoreactive, as were the presubiculum/subiculum regions and dentate gyrus granule cells of the hippocampus. The CA zones of the hippocampus were not immunoreactive. Preliminary data from immunoblotting experiments indicate that PEP-19 immunoreactivity is significantly reduced in cerebellum in Alzheimer's disease. While there were no apparent alterations of immunoreactivity in Down's syndrome or in Parkinson's disease, immunohistochemical analysis showed a massive loss of PEP-19 immunoreactivity in the caudate nucleus, putamen, globus pallidus and substantia nigra in Huntington's disease. These results show that PEP-19, a neuron-specific, calmodulin-binding protein, is distributed in specific areas of the adult human brain. The reduction in PEP-19 immunoreactivity in Alzheimer's disease and Huntington's disease suggests that PEP-19 may play a role in the pathophysiology of these diseases through a mechanism of calcium/calmodulin disregulation. This may be especially apparent in Huntington's disease where the distribution of the product of the abnormal gene, huntingtin, alone is not sufficient to explain the pattern of pathology. Abnormal huntingtin associates more strongly with calmodulin than does normal huntingtin [Bao et al. (1996) Proc. natn. Acad Sci. U.S.A., 93. 5037 5042] suggesting a disruption of calmodulin-mediated intracellular mechanism(s), very likely involving PEP-19.

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