Early signs of colonic inflammation, intestinal dysfunction, and olfactory impairments in the rotenone-induced mouse model of Parkinson’s disease

Abstract

The factors that trigger the pathophysiology of Parkinson's disease (PD) are unknown. However, it is suggested that environmental factors, such as exposure to pesticides, play an important role, in addition to genetic predisposition and aging. Early signs of PD can appear in the gastrointestinal (GI) tract and in the olfactory system, preceding the onset of motor impairments by many years. The present study assessed the effects of oral rotenone administration (30 mg/kg) in inducing GI and olfactory dysfunctions associated with PD in mice. Here we show that rotenone transiently increased myeloperoxidase activity within 24 h of administration. Leucocyte infiltration in the colon, associated with histological damage and disrupted GI motility, were observed following treatment with rotenone for 7 days. Moreover, 7 days of treatment with rotenone disrupted olfactory discrimination in mice without affecting social recognition ability. The presence of specific deficits in olfactory function occurred with a concomitant decrease in tyrosine hydroxylase-positive neurons and an increase in serotonin (5-hydroxytryptamine) turnover in the olfactory bulb. These findings suggest that in Swiss mice, exposure to rotenone induces GI and olfactory dysfunction involving immunological and neurotransmitter alterations, similar to early signs of PD. This provides further evidence for the involvement of the gut-brain axis in PD.

Is the Exposome Involved in Brain Disorders through the Serotoninergic System?

“…These results suggest that exposure to rotenone induces GI and olfactory dysfunction involving immunological and neurotransmitter alterations, similar to the early signs of PD. This provides further evidence for the involvement of the gut-brain axis in PD [99]. Paraquat, a widely used herbicide in the world, leads to the apoptosis of dopaminergic cells [100].…”

Parkinson’s Disease and the Gut: Future Perspectives for Early Diagnosis

“…These changes may affect the local immune response, which leads to disruption of the mucosal barrier of the GIT and subsequent inflammatory reactions. Systemic inflammation as a result of migrated gut bacteria and cytokines may results in an impairment of BBB, progressively to neuroinflammation and through the over-response of the CNS immune system or CNS inflammatory response to neurodegeneration (Maes and Leunis, 2008;Clairembault et al, 2015b;Yang et al, 2017;Morais et al, 2018;Perez-Pardo et al, 2018;Dodiya et al, 2020). However, the role of the intestinal microbiota in the initiation and progression of PDrelated pathology is currently unclear, as well as whether these changes in the intestinal microbiome are the cause or consequence of aS-related pathology.…”

Minireview on the Relations between Gut Microflora and Parkinson’s Disease: Further Biochemical (Oxidative Stress), Inflammatory, and Neurological Particularities

“…In rotenone models, chronic stress induces a deregulation of HPA which may culminate in dysbacteriosis, characterised by a significant reduction in the number of species belonging to the genus Bifidobacterium, to the detriment of Escherichia coli. Prolonged exposure leads to an increased intestinal permeability which creates a "leaky gut," dysosmia, and colitis by inducing specific neuroanatomical and neurochemical changes [55][56][57][58][59].…”