Bmal1 mediates the neuroprotective effect of sodium butyrate in a mouse model of Parkinson's disease
10.12122/j.issn.1673-4254.2024.05.09
- VernacularTitle:Bmal1可能介导了丁酸钠对帕金森病小鼠的神经保护作用
- Author:
Feixia WANG
1
,
2
,
3
;
Zheng ZHANG
;
Yan SUN
;
Liujing YANG
;
Tongtong GUO
;
Yeting PAN
;
Songtao DING
;
Lin JIANG
;
Handeng LIU
Author Information
1. 重庆医科大学 实验教学管理中心组织与细胞生物学实验室,重庆 400016
2. 重庆医科大学 神经科学研究中心,重庆 400016
3. 重庆医科大学 基础医学院,重庆 400016
- Keywords:
sodium butyrate;
Parkinson's disease;
gut-brain axis;
Bmal1
- From:
Journal of Southern Medical University
2024;44(5):876-884
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanisms that mediate the neuroprotective effect of the intestinal microbial metabolite sodium butyrate(NaB)in a mouse model of Parkinson's disease(PD)via the gut-brain axis.Methods Thirty-nine 7-week-old male C57BL/6J mice were randomized equally into control group,PD model group,and NaB treatment group.In the latter two groups,PD models were established by intraperitoneal injection of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once daily for 5 consecutive days,and normal saline was injected in the control group.After modeling,the mice received daily gavage of NaB(300 mg/kg)or an equal volume of saline for 14 days.Behavioral tests were carried out to assess the changes in motor function of the mice,and Western blotting was performed to detect the expressions of tyrosine hydroxylase(TH)and α-synuclein(α-syn)in the striatum and nuclear factor-κB(NF-κB),tumor necrosis factor(TNF-α),interleukin 6(IL-6),and the tight junction proteins ZO-1,Occludin,and Claudinin the colon.HE staining was used to observe inflammatory cell infiltration in the colon of the mice.RNA sequencing analysis was performed to identify the differentially expressed genes in mouse colon tissues,and their expressions were verified using qRT-PCR and Western blotting.Results The mouse models of PD with NaB treatment showed significantly increased movement speed and pulling strength of the limbs with obviously upregulated expressions of TH,Occludin,and Claudin and downregulated expressions of α-syn,NF-κB,TNF-α,and IL-6(all P<0.05).HE staining showed that NaB treatment significantly ameliorated inflammatory cell infiltration in the colon of the PD mice.RNA sequencing suggested that Bmal1 gene probably mediated the neuroprotective effect of NaB in PD mice(P<0.05).Conclusion NaB can improve motor dysfunction,reduce dopaminergic neuron loss in the striatum,and ameliorate colonic inflammation in PD mice possibly through a mechanism involving Bmal1.
