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H MRS identifies lactate rise in the striatum of MPTP-treated C57BL/6 mice.
Eur J Neurosci. 2006 Feb; 23(4):1077-81.EJ

Abstract

Mitochondrial dysfunction has been implicated in the death of nigrostriatal dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated experimental models of Parkinson's disease (PD). Here we utilized proton magnetic resonance spectroscopy ((1)H MRS) to identify changes in energy metabolism in the striatum of MPTP-treated C57BL/6 mice. Remarkable increases in lactate/creatine (Lac/Cr) ratio were observed at 2 h and then quickly returned to about the basal level by 7 h after injection of MPTP. Neurochemical and Western blot analyses revealed that dopamine contents and protein levels of tyrosine hydroxylase and dopamine transporter in the striatum were profoundly decreased at 3 days after MPTP treatment. Pretreatment with deprenyl, a monoamine oxidase B inhibitor, or GBR-12909, a dopamine uptake inhibitor, almost completely attenuated both the increases in striatal Lac/Cr ratio and the subsequent loss of dopaminergic nerve terminals in MPTP-treated mice. The present study indicates that (1)H MRS is a sensitive measure of biochemical alterations of the brain in a mouse model of PD, and further shows that the increases in striatal Lac/Cr ratio induced by MPTP may be associated with mitochondrial energy crisis, followed by dopaminergic neurotoxicity.

Authors+Show Affiliations

Laboratory of Bioenergetics Research, Tokushima Research Institute, Otsuka Pharmaceutical Co. Ltd, Tokushima 771-0192, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16519673

Citation

Koga, Keiko, et al. "H MRS Identifies Lactate Rise in the Striatum of MPTP-treated C57BL/6 Mice." The European Journal of Neuroscience, vol. 23, no. 4, 2006, pp. 1077-81.
Koga K, Mori A, Ohashi S, et al. H MRS identifies lactate rise in the striatum of MPTP-treated C57BL/6 mice. Eur J Neurosci. 2006;23(4):1077-81.
Koga, K., Mori, A., Ohashi, S., Kurihara, N., Kitagawa, H., Ishikawa, M., Mitsumoto, Y., & Nakai, M. (2006). H MRS identifies lactate rise in the striatum of MPTP-treated C57BL/6 mice. The European Journal of Neuroscience, 23(4), 1077-81.
Koga K, et al. H MRS Identifies Lactate Rise in the Striatum of MPTP-treated C57BL/6 Mice. Eur J Neurosci. 2006;23(4):1077-81. PubMed PMID: 16519673.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - H MRS identifies lactate rise in the striatum of MPTP-treated C57BL/6 mice. AU - Koga,Keiko, AU - Mori,Atsushi, AU - Ohashi,Satoshi, AU - Kurihara,Naoki, AU - Kitagawa,Hisashi, AU - Ishikawa,Makoto, AU - Mitsumoto,Yasuhide, AU - Nakai,Masami, PY - 2006/3/8/pubmed PY - 2006/5/10/medline PY - 2006/3/8/entrez SP - 1077 EP - 81 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 23 IS - 4 N2 - Mitochondrial dysfunction has been implicated in the death of nigrostriatal dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated experimental models of Parkinson's disease (PD). Here we utilized proton magnetic resonance spectroscopy ((1)H MRS) to identify changes in energy metabolism in the striatum of MPTP-treated C57BL/6 mice. Remarkable increases in lactate/creatine (Lac/Cr) ratio were observed at 2 h and then quickly returned to about the basal level by 7 h after injection of MPTP. Neurochemical and Western blot analyses revealed that dopamine contents and protein levels of tyrosine hydroxylase and dopamine transporter in the striatum were profoundly decreased at 3 days after MPTP treatment. Pretreatment with deprenyl, a monoamine oxidase B inhibitor, or GBR-12909, a dopamine uptake inhibitor, almost completely attenuated both the increases in striatal Lac/Cr ratio and the subsequent loss of dopaminergic nerve terminals in MPTP-treated mice. The present study indicates that (1)H MRS is a sensitive measure of biochemical alterations of the brain in a mouse model of PD, and further shows that the increases in striatal Lac/Cr ratio induced by MPTP may be associated with mitochondrial energy crisis, followed by dopaminergic neurotoxicity. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/16519673/H_MRS_identifies_lactate_rise_in_the_striatum_of_MPTP_treated_C57BL/6_mice_ L2 - https://doi.org/10.1111/j.1460-9568.2006.04610.x DB - PRIME DP - Unbound Medicine ER -