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Systemic proteasomal inhibitor exposure enhances dopamine turnover and decreases dopamine levels but does not affect MPTP-induced striatal dopamine depletion in mice.
Synapse. 2008 Feb; 62(2):85-90.S

Abstract

The validation of an in vivo proteasomal inhibitor (PSI) model to translate ubiquitin-proteasomal-system dysfunction involved in the pathogenesis of Parkinson's disease (PD) into a commonly accepted animal model is ongoing. Here we first report the effects of systemic administration of the proteasomal inhibitor Z-lle-Glu(OtBu)-Ala-Leu-CHO (3 mg/kg, s.c., six times over 2 weeks) alone to extend the rat model to mice. Second we investigate the consequences of PSI pretreatment 42 weeks before an acute treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57bl/6 mice. HPLC postmortem neurochemistry showed a significant increase in dopamine turnover and decrease of striatal dopamine levels, only 14 weeks after PSI treatment, but no enhancement of dopamine turnover or differences in striatal dopamine levels when comparing MPTP with MPTP plus PSI treatment. Behavioral analysis (rotarod, open field activity) did not indicate that PSI affects this type of motor behavior. Systemic PSI administration in mice appears not to be a valid animal model under the experimental conditions used. Potential solutions are discussed.

Authors+Show Affiliations

Department of CNS Research, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach, Germany.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17992685

Citation

Hirst, Sarah J., and Boris Ferger. "Systemic Proteasomal Inhibitor Exposure Enhances Dopamine Turnover and Decreases Dopamine Levels but Does Not Affect MPTP-induced Striatal Dopamine Depletion in Mice." Synapse (New York, N.Y.), vol. 62, no. 2, 2008, pp. 85-90.
Hirst SJ, Ferger B. Systemic proteasomal inhibitor exposure enhances dopamine turnover and decreases dopamine levels but does not affect MPTP-induced striatal dopamine depletion in mice. Synapse. 2008;62(2):85-90.
Hirst, S. J., & Ferger, B. (2008). Systemic proteasomal inhibitor exposure enhances dopamine turnover and decreases dopamine levels but does not affect MPTP-induced striatal dopamine depletion in mice. Synapse (New York, N.Y.), 62(2), 85-90.
Hirst SJ, Ferger B. Systemic Proteasomal Inhibitor Exposure Enhances Dopamine Turnover and Decreases Dopamine Levels but Does Not Affect MPTP-induced Striatal Dopamine Depletion in Mice. Synapse. 2008;62(2):85-90. PubMed PMID: 17992685.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Systemic proteasomal inhibitor exposure enhances dopamine turnover and decreases dopamine levels but does not affect MPTP-induced striatal dopamine depletion in mice. AU - Hirst,Sarah J, AU - Ferger,Boris, PY - 2007/11/10/pubmed PY - 2008/3/22/medline PY - 2007/11/10/entrez SP - 85 EP - 90 JF - Synapse (New York, N.Y.) JO - Synapse VL - 62 IS - 2 N2 - The validation of an in vivo proteasomal inhibitor (PSI) model to translate ubiquitin-proteasomal-system dysfunction involved in the pathogenesis of Parkinson's disease (PD) into a commonly accepted animal model is ongoing. Here we first report the effects of systemic administration of the proteasomal inhibitor Z-lle-Glu(OtBu)-Ala-Leu-CHO (3 mg/kg, s.c., six times over 2 weeks) alone to extend the rat model to mice. Second we investigate the consequences of PSI pretreatment 42 weeks before an acute treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57bl/6 mice. HPLC postmortem neurochemistry showed a significant increase in dopamine turnover and decrease of striatal dopamine levels, only 14 weeks after PSI treatment, but no enhancement of dopamine turnover or differences in striatal dopamine levels when comparing MPTP with MPTP plus PSI treatment. Behavioral analysis (rotarod, open field activity) did not indicate that PSI affects this type of motor behavior. Systemic PSI administration in mice appears not to be a valid animal model under the experimental conditions used. Potential solutions are discussed. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/17992685/Systemic_proteasomal_inhibitor_exposure_enhances_dopamine_turnover_and_decreases_dopamine_levels_but_does_not_affect_MPTP_induced_striatal_dopamine_depletion_in_mice_ L2 - https://doi.org/10.1002/syn.20457 DB - PRIME DP - Unbound Medicine ER -