[Protective effects of doxycycline upon dopaminergic neuron in LPS-induced rat model of Parkinson's disease].
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.
Wang
Pu-qing
PQ
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Sun
Sheng-gang
SG
Qiao
Xian
X
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015536:Down-Regulation; D004318:Doxycycline / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D008070:Lipopolysaccharides / Q000009:adverse effects; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D004318:Doxycycline; D004298:Dopamine