Abstract
Parkinson's disease (PD) is a common degenerative disease of the central nervous system. Although some drugs can alleviate the progress of PD, their long-term use will lead to complications, so it is still necessary to find new drugs to delay or cure PD effectively. In view of the difficulty in developing new drugs, it is imperative to discover new functions of existing compounds that could be used to treat PD. In this study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce PD symptoms in a mouse model. Subsequently, these mice were treated with the antibiotic ceftriaxone. Ceftriaxone alleviated the behavioural and neuropathological changes induced by MPTP, downregulated the expression of glial fibrillary acidic protein (GFAP) and ionised calcium-binding adapter molecule 1 (Iba1) as markers of astroglia and microglia, respectively, and reduced the expression of neuroinflammation-related Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and phosphorylated nuclear factor kappa-B (p-NF-κB)/NF-κB in the brain of PD mice. In addition, ceftriaxone reduced the abundance of pathogenic bacteria of the genus Proteus and increased the abundance of probiotic Akkermansia. Finally, ceftriaxone treatment increased the expression of the tight junction proteins zona occludens-1(ZO-1) and occludin in the colon, decreased the expression of the inflammation-related proteins TLR4, MyD88, and NF-κB in the colon, and decreased the serum concentration of the proinflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α). These results indicate that ceftriaxone had a neuroprotective effect on MPTP-induced PD mice, and its neuroprotective effect could be through regulating inflammation and intestinal microbiota. While we showed that ceftriaxone exerts a neuroprotective effect in an MPTP-induced PD mouse model, our findings are limited to the short-term effects of ceftriaxone. Additional work using transgenic mice is required to determine the long-term effects of ceftriaxone. In addition, the dose and frequency of ceftriaxone use should be evaluated.
Highlights
Parkinson’s disease (PD) is a complex and progressively degenerative disease of the central nervous system; it affects more than 6 million people throughout the world [1]
MPTP-treated mice showed significant motor dysfunction compared with the control group (M vs:C = 17:72 s vs:10:89 s; p < 0:001), and ceftriaxone significantly alleviated MPTP-induced motor dysfunction (MCEF vs:M = 11:67 s vs:17:72 s; p < 0:001), and motor dysfunction recurred in the MCEFF group, which underwent transplantation of faecal microbiota from PD mice (MCEFF vs:MCEF = 13:83 s vs:11:67 s) (Figure 1(b))
When we transplanted the faecal microbiota of PD mice to normal mice, the mice in the FMT group showed motor impairment compared with the control group (FMT vs:C = 15:74 s vs 10:89 s; p < 0:01)
Summary
Parkinson’s disease (PD) is a complex and progressively degenerative disease of the central nervous system; it affects more than 6 million people throughout the world [1]. The clinical features of PD include motor and nonmotor symptoms [2]. These symptoms severely affect the quality of life of patients and bring great burden to society [3]. The main pathologies of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) of the midbrain and the accumulation of α-synuclein in the cytoplasm of neurons form Lewy bodies. The aetiology of PD is not clear but may be related to various risk factors such as excitotoxicity, oxidative stress, and neuroinflammation.
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