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Substantial telomere shortening in the substantia nigra of telomerase-deficient mice does not increase susceptibility to MPTP-induced dopamine depletion.
Neuroreport. 2014 Mar 26; 25(5):335-9.N

Abstract

The most important risk factor for developing Parkinson's disease (PD) is age. Aging is ascribed to different mechanisms, including telomere shortening. Telomeres consist of repetitive DNA sequences and stabilize chromosome integrity. Currently, however, the data reported on telomere shortening in PD patients are inconsistent. We investigated the effect of telomere shortening in the MPTP mouse model of PD using late-generation telomerase-deficient mice (G3 Terc mice). G3 Terc mice showed a reduction in telomere length in nigral tyrosine hydroxylase-positive neurons by 40%, as indicated by quantitative fluorescence in-situ hybridization. There was no difference in the total motor activity and striatal tissue concentrations of dopamine, DOPAC (3,4-dihydroxyphenylacetic acid), HVA (4-hydroxy-3-methoxyphenylacetic acid), and 3-MT (3-methoxytyramine) concentrations or dopamine turnover in G3 Terc mice in comparison with controls without MPTP treatment. Low-dose MPTP treatment (four injections, 2 h intervals, 2 × 5 and 2 × 7.5 mg/kg) led to a significant decrease in striatal dopamine concentrations that did not differ in G3 Terc mice compared with control mice (19.15 ± 0.44 to 12.81 ± 1.26 ng/mg in control mice in comparison with 19.51 ± 0.59 to 13.56 ± 1.10 ng/mg in G3 Terc mice). In conclusion, telomere shortening does not increase susceptibility to MPTP-induced dopamine depletion in mice. These data indicate that other age-related mechanisms in the brain may play a more important role in enhancing MPTP-induced dopamine depletion.

Authors+Show Affiliations

aCNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss bInstitute of Molecular Medicine and Max-Planck-Research-Group on Stem Cell Ageing, University of Ulm, Ulm, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24525820

Citation

Oeckl, Patrick, et al. "Substantial Telomere Shortening in the Substantia Nigra of Telomerase-deficient Mice Does Not Increase Susceptibility to MPTP-induced Dopamine Depletion." Neuroreport, vol. 25, no. 5, 2014, pp. 335-9.
Oeckl P, Scheffold A, Lechel A, et al. Substantial telomere shortening in the substantia nigra of telomerase-deficient mice does not increase susceptibility to MPTP-induced dopamine depletion. Neuroreport. 2014;25(5):335-9.
Oeckl, P., Scheffold, A., Lechel, A., Rudolph, K. L., & Ferger, B. (2014). Substantial telomere shortening in the substantia nigra of telomerase-deficient mice does not increase susceptibility to MPTP-induced dopamine depletion. Neuroreport, 25(5), 335-9. https://doi.org/10.1097/WNR.0000000000000099
Oeckl P, et al. Substantial Telomere Shortening in the Substantia Nigra of Telomerase-deficient Mice Does Not Increase Susceptibility to MPTP-induced Dopamine Depletion. Neuroreport. 2014 Mar 26;25(5):335-9. PubMed PMID: 24525820.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Substantial telomere shortening in the substantia nigra of telomerase-deficient mice does not increase susceptibility to MPTP-induced dopamine depletion. AU - Oeckl,Patrick, AU - Scheffold,Annika, AU - Lechel,André, AU - Rudolph,K Lenhard, AU - Ferger,Boris, PY - 2014/2/15/entrez PY - 2014/2/15/pubmed PY - 2014/12/15/medline SP - 335 EP - 9 JF - Neuroreport JO - Neuroreport VL - 25 IS - 5 N2 - The most important risk factor for developing Parkinson's disease (PD) is age. Aging is ascribed to different mechanisms, including telomere shortening. Telomeres consist of repetitive DNA sequences and stabilize chromosome integrity. Currently, however, the data reported on telomere shortening in PD patients are inconsistent. We investigated the effect of telomere shortening in the MPTP mouse model of PD using late-generation telomerase-deficient mice (G3 Terc mice). G3 Terc mice showed a reduction in telomere length in nigral tyrosine hydroxylase-positive neurons by 40%, as indicated by quantitative fluorescence in-situ hybridization. There was no difference in the total motor activity and striatal tissue concentrations of dopamine, DOPAC (3,4-dihydroxyphenylacetic acid), HVA (4-hydroxy-3-methoxyphenylacetic acid), and 3-MT (3-methoxytyramine) concentrations or dopamine turnover in G3 Terc mice in comparison with controls without MPTP treatment. Low-dose MPTP treatment (four injections, 2 h intervals, 2 × 5 and 2 × 7.5 mg/kg) led to a significant decrease in striatal dopamine concentrations that did not differ in G3 Terc mice compared with control mice (19.15 ± 0.44 to 12.81 ± 1.26 ng/mg in control mice in comparison with 19.51 ± 0.59 to 13.56 ± 1.10 ng/mg in G3 Terc mice). In conclusion, telomere shortening does not increase susceptibility to MPTP-induced dopamine depletion in mice. These data indicate that other age-related mechanisms in the brain may play a more important role in enhancing MPTP-induced dopamine depletion. SN - 1473-558X UR - https://www.unboundmedicine.com/medline/citation/24525820/Substantial_telomere_shortening_in_the_substantia_nigra_of_telomerase_deficient_mice_does_not_increase_susceptibility_to_MPTP_induced_dopamine_depletion_ L2 - https://doi.org/10.1097/WNR.0000000000000099 DB - PRIME DP - Unbound Medicine ER -