MPTP administration in mice changes the ratio of splice isoforms of fosB and rgs9

Judith A. Potashkin, Un Jung Kang, Patricia A. Loomis, Francine M. Jodelka, Yunmin Ding, Gloria E. Meredith

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Abstract

Most cases of Parkinson's disease (PD) are sporadic, suggesting an environmental influence on individuals affected by this neurodegenerative disorder. Environmental stresses often lead to changes in the regulation of splicing of pre-mRNA transcripts and this may lead to the pathogenesis of the disease. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid mouse model was used to examine the changes in the splicing of the fosB and rgs9 transcripts. The ratio of ΔfosB/fosB transcript was decreased in the substantia nigra and unchanged in the striatum after acute MPTP treatment. The ΔfosB/fosB transcript ratio decreased initially and then increased in the striatum of chronically MPTP-treated animals due to different degrees of reduction for the splice variants over time, whereas the ratio was unchanged in the substantia nigra. The ratio of rgs9-2/rgs9-1 transcript decreased in the substantia nigra of mice after acute MPTP treatment and increased temporarily in the striatum after chronic MPTP treatment. There was an increase in the ΔFosB/FosB and RGS9-2/RGS9-1 protein ratios 3 weeks and 3 days post-treatment, respectively, in chronically treated mice. The data indicate that the pattern of splice isoforms of fosB and rgs9 reflects the brain's immediate and long-term responses to the physiological stress associated with Parkinsonism.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalBrain Research
Volume1182
Issue number1
DOIs
StatePublished - 28 Nov 2007

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Protein Isoforms
Substantia Nigra
Probenecid
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Physiological Stress
RNA Precursors
Parkinsonian Disorders
Neurodegenerative Diseases
Parkinson Disease
4-phenyl-1,2,3,6-tetrahydropyridine
Brain
Proteins

Keywords

  • Dopamine
  • FosB
  • MPTP
  • Neurodegeneration
  • Pre-mRNA splicing
  • RGS9

Cite this

Potashkin, J. A., Kang, U. J., Loomis, P. A., Jodelka, F. M., Ding, Y., & Meredith, G. E. (2007). MPTP administration in mice changes the ratio of splice isoforms of fosB and rgs9. Brain Research, 1182(1), 1-10. https://doi.org/10.1016/j.brainres.2007.08.080
Potashkin, Judith A. ; Kang, Un Jung ; Loomis, Patricia A. ; Jodelka, Francine M. ; Ding, Yunmin ; Meredith, Gloria E. / MPTP administration in mice changes the ratio of splice isoforms of fosB and rgs9. In: Brain Research. 2007 ; Vol. 1182, No. 1. pp. 1-10.
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Potashkin, JA, Kang, UJ, Loomis, PA, Jodelka, FM, Ding, Y & Meredith, GE 2007, 'MPTP administration in mice changes the ratio of splice isoforms of fosB and rgs9', Brain Research, vol. 1182, no. 1, pp. 1-10. https://doi.org/10.1016/j.brainres.2007.08.080

MPTP administration in mice changes the ratio of splice isoforms of fosB and rgs9. / Potashkin, Judith A.; Kang, Un Jung; Loomis, Patricia A.; Jodelka, Francine M.; Ding, Yunmin; Meredith, Gloria E.

In: Brain Research, Vol. 1182, No. 1, 28.11.2007, p. 1-10.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - MPTP administration in mice changes the ratio of splice isoforms of fosB and rgs9

AU - Potashkin, Judith A.

AU - Kang, Un Jung

AU - Loomis, Patricia A.

AU - Jodelka, Francine M.

AU - Ding, Yunmin

AU - Meredith, Gloria E.

PY - 2007/11/28

Y1 - 2007/11/28

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AB - Most cases of Parkinson's disease (PD) are sporadic, suggesting an environmental influence on individuals affected by this neurodegenerative disorder. Environmental stresses often lead to changes in the regulation of splicing of pre-mRNA transcripts and this may lead to the pathogenesis of the disease. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid mouse model was used to examine the changes in the splicing of the fosB and rgs9 transcripts. The ratio of ΔfosB/fosB transcript was decreased in the substantia nigra and unchanged in the striatum after acute MPTP treatment. The ΔfosB/fosB transcript ratio decreased initially and then increased in the striatum of chronically MPTP-treated animals due to different degrees of reduction for the splice variants over time, whereas the ratio was unchanged in the substantia nigra. The ratio of rgs9-2/rgs9-1 transcript decreased in the substantia nigra of mice after acute MPTP treatment and increased temporarily in the striatum after chronic MPTP treatment. There was an increase in the ΔFosB/FosB and RGS9-2/RGS9-1 protein ratios 3 weeks and 3 days post-treatment, respectively, in chronically treated mice. The data indicate that the pattern of splice isoforms of fosB and rgs9 reflects the brain's immediate and long-term responses to the physiological stress associated with Parkinsonism.

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KW - FosB

KW - MPTP

KW - Neurodegeneration

KW - Pre-mRNA splicing

KW - RGS9

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M3 - Article

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