Abstract:
:L-DOPA (L-3,4-dihydroxyphenylalanine) relieves symptoms of Parkinson disease (PD), but long-term use can cause serious side effects. Resveratrol (3,5,4'-trihydroxy-trans-stilbene, RV), a polyphenolic compound derived from grapes and red wine that has antioxidant activity, has been shown to have neuroprotective effects. RV was investigated to enhance the therapeutic effect of L-DOPA in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse model of Parkinson disease. Mice received a saline or RV injection (10 mg/kg/day), then 2 h later, saline or MPTP (15 mg/kg/day) was administered for 7 consecutive days. Saline or L-DOPA (5 or 8 mg/kg/day) was injected post-administration of MPTP for the last 2 consecutive days. Our results indicated that RV alleviated MPTP-induced loss of dopaminergic neurons and attenuated astroglial activation in the nigrostriatal pathway. In parallel, RV reduced the expression of α-synuclein in the striatum. In addition, RV also increased levels of the anti-apoptotic signalling molecule Bcl-2, reduced levels of the pro-apoptotic signalling molecule Bax, and reduced activation of caspase-3 in the striatum. Specifically, RV significantly reduced motor dysfunction in MPTP-treated mice. Furthermore, the RV-treated group showed less IL-1β and an enhanced pAkt/Akt ratio, which promoted dopamine neuron survival in the striatum. We found that the effects of co-administration of RV with L-DOPA (5 mg/kg) were equivalent to those of administration of 8 mg/kg L-DOPA in MPTP-induced PD mice. Therefore, with fewer side effects, L-DOPA can be effectively used in the treatment of PD over a long period of time.
journal_name
Behav Brain Resjournal_title
Behavioural brain researchauthors
Liu Q,Zhu D,Jiang P,Tang X,Lang Q,Yu Q,Zhang S,Che Y,Feng Xdoi
10.1016/j.bbr.2019.03.043subject
Has Abstractpub_date
2019-07-23 00:00:00pages
10-18eissn
0166-4328issn
1872-7549pii
S0166-4328(19)30201-3journal_volume
367pub_type
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