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[Protective effects of doxycycline upon dopaminergic neuron in LPS-induced rat model of Parkinson's disease].

Abstract

OBJECTIVE

To explore the protective effect of doxycycline (DC) upon dopaminergic neuron in lipopolysaccharide (LPS)-induce rat model of Parkinson's disease (PD).

METHODS

Sixty SD rats were randomly divided into three groups: control, LPS and doxycycline treatment. LPS was stereotatically injected into unilateral substantia nigra (SNc) of rats to establish the PD models. The damage to the substantia nigra DA neurons was observed by using tyrosine-hydroxylase (TH) immunohistochemical staining. Specific antibody OX6 (MHCII marker) was used to detect the changes in morphology and the numbers of microglia. The contents of dopamine and DOPAC in striatum were measured by high performance liquid chromatography (HPLC). Western blot were used to detect the expression of MHCII (Major histocompatibility complex class II) protein.

RESULTS

After doxycycline treatment, the number of TH-positive cells remaining in the SNc increased from 38% +/- 5% to 79% +/- 4% (P < 0.01). The contents of dopamine and DOPAC in striatum increased from 4.89 +/- 0.27 and 0.70 +/- 0.07 to 7.00 +/- 0.34 and 1.10 +/- 0.10 respectively (P < 0.01); there was a significant decrease in rotational asymmetry in the doxycycline treatment group [(80 +/- 12) turns/30 min] when compared to the LPS group [(208 +/- 14) turns/30 min] (P < 0.01). However, the number of MHCII-positive microglia decreased significantly (LPS group: 835 +/- 82 vs doxycycline treatment group: 354 +/- 59, P < 0.01) after doxycycline treatment. Western blot were used to detect the expression of MHCII protein. The results showed that the expression of MHCII protein on microglia of LPS group increased significantly compared to the control group, but the expression of MHCII protein were inhibited significantly after doxycycline treatment in the doxycycline treatment group, as compared to the LPS group.

CONCLUSIONS

Doxycycline might inhibit dopaminergic neuron degeneration by down-regulating the MHCII expression on microglia.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

    ,

    Source

    Zhonghua yi xue za zhi 89:19 2009 May 19 pg 1346-50

    MeSH

    Animals
    Corpus Striatum
    Disease Models, Animal
    Dopamine
    Down-Regulation
    Doxycycline
    Female
    Gene Expression Regulation
    Genes, MHC Class II
    Lipopolysaccharides
    Microglia
    Neurons
    Parkinson Disease
    Rats
    Rats, Sprague-Dawley

    Pub Type(s)

    English Abstract
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    chi

    PubMed ID

    19615192

    Citation

    Wang, Pu-qing, et al. "[Protective Effects of Doxycycline Upon Dopaminergic Neuron in LPS-induced Rat Model of Parkinson's Disease]." Zhonghua Yi Xue Za Zhi, vol. 89, no. 19, 2009, pp. 1346-50.
    Wang PQ, Sun SG, Qiao X. [Protective effects of doxycycline upon dopaminergic neuron in LPS-induced rat model of Parkinson's disease]. Zhonghua Yi Xue Za Zhi. 2009;89(19):1346-50.
    Wang, P. Q., Sun, S. G., & Qiao, X. (2009). [Protective effects of doxycycline upon dopaminergic neuron in LPS-induced rat model of Parkinson's disease]. Zhonghua Yi Xue Za Zhi, 89(19), pp. 1346-50.
    Wang PQ, Sun SG, Qiao X. [Protective Effects of Doxycycline Upon Dopaminergic Neuron in LPS-induced Rat Model of Parkinson's Disease]. Zhonghua Yi Xue Za Zhi. 2009 May 19;89(19):1346-50. PubMed PMID: 19615192.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - [Protective effects of doxycycline upon dopaminergic neuron in LPS-induced rat model of Parkinson's disease]. AU - Wang,Pu-qing, AU - Sun,Sheng-gang, AU - Qiao,Xian, PY - 2009/7/21/entrez PY - 2009/7/21/pubmed PY - 2009/11/18/medline SP - 1346 EP - 50 JF - Zhonghua yi xue za zhi JO - Zhonghua Yi Xue Za Zhi VL - 89 IS - 19 N2 - OBJECTIVE: To explore the protective effect of doxycycline (DC) upon dopaminergic neuron in lipopolysaccharide (LPS)-induce rat model of Parkinson's disease (PD). METHODS: Sixty SD rats were randomly divided into three groups: control, LPS and doxycycline treatment. LPS was stereotatically injected into unilateral substantia nigra (SNc) of rats to establish the PD models. The damage to the substantia nigra DA neurons was observed by using tyrosine-hydroxylase (TH) immunohistochemical staining. Specific antibody OX6 (MHCII marker) was used to detect the changes in morphology and the numbers of microglia. The contents of dopamine and DOPAC in striatum were measured by high performance liquid chromatography (HPLC). Western blot were used to detect the expression of MHCII (Major histocompatibility complex class II) protein. RESULTS: After doxycycline treatment, the number of TH-positive cells remaining in the SNc increased from 38% +/- 5% to 79% +/- 4% (P < 0.01). The contents of dopamine and DOPAC in striatum increased from 4.89 +/- 0.27 and 0.70 +/- 0.07 to 7.00 +/- 0.34 and 1.10 +/- 0.10 respectively (P < 0.01); there was a significant decrease in rotational asymmetry in the doxycycline treatment group [(80 +/- 12) turns/30 min] when compared to the LPS group [(208 +/- 14) turns/30 min] (P < 0.01). However, the number of MHCII-positive microglia decreased significantly (LPS group: 835 +/- 82 vs doxycycline treatment group: 354 +/- 59, P < 0.01) after doxycycline treatment. Western blot were used to detect the expression of MHCII protein. The results showed that the expression of MHCII protein on microglia of LPS group increased significantly compared to the control group, but the expression of MHCII protein were inhibited significantly after doxycycline treatment in the doxycycline treatment group, as compared to the LPS group. CONCLUSIONS: Doxycycline might inhibit dopaminergic neuron degeneration by down-regulating the MHCII expression on microglia. SN - 0376-2491 UR - https://www.unboundmedicine.com/medline/citation/19615192/[Protective_effects_of_doxycycline_upon_dopaminergic_neuron_in_LPS_induced_rat_model_of_Parkinson's_disease]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&amp;issn=0376-2491&amp;year=2009&amp;vol=89&amp;issue=19&amp;fpage=1346 DB - PRIME DP - Unbound Medicine ER -