Atrophy and loss of dopaminergic mesencephalic neurons in heterozygous weaver mice

Tatyana Verina, James A. Norton, Jeffrey J. Sorbel, Lazaros C. Triarhou, Donald Laferty, Judith A. Richter, Jay R. Simon, Bernardino Ghetti

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Abstract

The phenotypic effect of the weaver mutation in the ventral midbrain of homozygous mutants is associated with the progressive loss of dopaminergic neurons. To discover whether the number of mesencephalic dopaminergic cells is altered in weaver heterozygotes (wv/+), we studied mice between 20 and 365 days of age. We counted tyrosine hydroxylase (TH)-immunopositive cells in the substantia nigra (SN), retrorubral nucleus (RRN), and ventral tegmental area (VTA), and measured cross-sectional areas of neuronal somata in the SN of wv/+ and age-matched wild-type controls (+/+). The number of TH-positive cells in the wv+ ventral midbrain was on average 13% lower than normal. Cell loss was detected selectively in the SN (12%) and VTA (23%). The areas of somatic profiles in the wv/+ nigral neurons were on average reduced by 9.8%. The neuronal losses in the SN and VTA correlated with a 13.8% reduction in dopamine level in the ventral striatum in wv/+ mice at 14-16 months of age. Our findings imply that a single dose of the weaver gene in the mouse is associated with cellular damage leading to a chronic deficiency in the mesostriatal dopaminergic system.

Original languageEnglish (US)
Pages (from-to)5-12
Number of pages8
JournalExperimental Brain Research
Volume113
Issue number1
DOIs
StatePublished - Jan 30 1997

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Keywords

  • Cell count
  • Heterozygous weaver mice
  • Midbrain dopamine neurons
  • Striatum
  • TH immunochemistry

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Verina, T., Norton, J. A., Sorbel, J. J., Triarhou, L. C., Laferty, D., Richter, J. A., Simon, J. R., & Ghetti, B. (1997). Atrophy and loss of dopaminergic mesencephalic neurons in heterozygous weaver mice. Experimental Brain Research, 113(1), 5-12. https://doi.org/10.1007/BF02454137