OBJECTIVETo investigate the neuroprotective effects and mechanisms of Chunxiong Chatiao pulvis (CXCT) on the MPTP-induced dopaminergic neurodegneration in mice model of PD.

METHODThree to five months old male mice were randomly divided into following six treatment groups (NS + NS, 50 mg x kg(-1) CXCT + NS, 25 mg x kg(-1) CXCT + MPTP, 50 mg x kg(-1) CXCT + MPTP, 75 mg x kg(-1) CXCT + MPTP, NS + MPTP) (n = 8/group). For behavioral measurement, the mice were evaluated for their motor coordination by pole-test; Striatal dopamine content of mice was measured using standard reverse-phase HPLC; Number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra of mice was detected by immunohistochemistry; SOD activity in the substantia nigra of mice were measured by fluorimetry.

RESULTThe score of pole test (25, 50, 75 mg x kg(-1)), the striatal dopamine contents (75 mg x kg-1), the residual DA contents (75 mg x kg(-1)) and the SOD activity in substantia nigra (50, 75 mg x kg(-1)) all showed that, the CXCT-pretreated groups significantly higher than that of the group NS + MPTP (P < 0.05 or P < 0.01).

CONCLUSIONChuanxiong Chatiao pulvis improved the motor deficit in MPTP-induced mice, and attenuate MPTP-induced dopaminergic neurodegeneration in mice. Importantly, the neuroprotective effect of Chuanxiong Chatiao pulvis against dopaminergic neurodegeneration may be associated with its strong antioxidant capacity in vivo.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; adverse effects ; Animals ; Disease Models, Animal ; Dopamine ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Male ; Mice ; Mice, Inbred C57BL ; Motor Activity ; drug effects ; Neuroprotective Agents ; administration & dosage ; Parkinson Disease ; drug therapy ; metabolism ; physiopathology ; Random Allocation

A wealth of evidence has suggested that gastrointestinal dysfunction is associated with the onset and progression of Parkinson's disease (PD). However, the mechanisms underlying these links remain to be defined. Here, we investigated the impact of deregulation of intestinal dopamine D2 receptor (DRD2) signaling in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration. Dopamine/dopamine signaling in the mouse colon decreased with ageing. Selective ablation of Drd2, but not Drd4, in the intestinal epithelium, caused a more severe loss of dopaminergic neurons in the substantia nigra following MPTP challenge, and this was accompanied by a reduced abundance of succinate-producing Alleoprevotella in the gut microbiota. Administration of succinate markedly attenuated dopaminergic neuronal loss in MPTP-treated mice by elevating the mitochondrial membrane potential. This study suggests that intestinal epithelial DRD2 activity and succinate from the gut microbiome contribute to the maintenance of nigral DA neuron survival. These findings provide a potential strategy targeting neuroinflammation-related neurological disorders such as PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects* ; Animals ; Disease Models, Animal ; Dopamine ; Dopaminergic Neurons/metabolism* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Neuroprotection ; Parkinson Disease ; Pyrrolidines ; Receptors, Dopamine D2/metabolism* ; Substantia Nigra ; Succinates