ObjectivesThe brain’s cholinergic system occupies a central role in normal cognition and age-related cognitive decline, including Alzheimer’s disease (AD). This study sought to investigate the role of antioxidant defense and cholinergic systems on rutin-induced antiamnesia in mice.MethodsRutin (1, 5, or 50 mg/kg, p.o.) or vehicle (10 ml/kg, p.o.) was administered for three consecutive days. One hour post-treatment on day 3, scopolamine (3 mg/kg, i.p) was given, 5 min post-scopolamine injection, open field, Y-maze, or Morris water maze (MWM) (five days consecutive training sessions) tasks was carried out. The mice were sacrificed on day 7 to assays for biomarkers of oxidative stress and cholinergic system.ResultsScopolamine significantly reduced spontaneous alternation behavior in Y-maze and prolonged escape latency in MWM tasks when compared to vehicle-treated control indicative of working memory and spatial learning deficits. However, the pretreatment of mice with rutin (1, 5, or 50 mg/kg) prevented scopolamine-induced working memory and spatial learning impairments without affecting spontaneous locomotor activity. Scopolamine-induced nitrosative/oxidative stress and increased acetylcholinesterase activity in the prefrontal cortex and hippocampus were significantly attenuated by the pretreatment of mice with rutin.Conclusionsrutin restored cognitive function in scopolamine-induced amnesia through enhancement of antioxidant defense and cholinergic systems.

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Background: Parkinson disease (PD) and Alzheimer’s disease (AD) are progressive neurodegenerative disorders characterized by loss of selective neurons in discreet part of the brain. The peptide angiotensin II (Ang II) plays significant role in hippocampal and striatal neurons degeneration through the generation of reactive oxygen species. Blockade of the angiotensin converting enzyme or ATI receptors provides protection in animal models of neurodegenerative diseases. In the present study, the neuroprotective effect of captopril was investigated in Drosophila melanogaster model using the UAS-GAL4 system to express the synuclein and Aβ42 peptide in the flies’ neurons. Methods: The disease causing human Aβ42 peptide or α-syn was expressed pan-neuronally (elav-GAL4) or dopamine neuron (DDC-GAL4) using the UAS-GAL4 system. Flies were either grown in food media with or without captopril (1, 5, or 10µM). This was followed by fecundity, larva motility, negative geotaxis assay (climbing) and lifespan as a measure of neurodegeneration. Results: Elav-Gal4<Aβ or DDC-GAL4<α-syn flies displayed significant decrease in larva motility when compared with normal control (w1118) which was reversed by the supplementation of the media with captopril (5 or 10 mM) indicative of neuroprotection. Interestingly, supplementation of flies’ media with captopril improved climbing activity in Elav-Gal4<Aβ or DDC-GAL4<α-syn flies when compared with vehicle treated only. Moreover, flies grown on captopril caused no significant change in lifespan.  Conclusion: Findings from this study confirmed the neuroprotective action of captopril in genetic or familial forms of neurodegeneration.

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Parkinson disease (PD) is a major public health challenge as many of the current drugs used in its management provide symptomatic relieve without preventing the underlying cause of the neurodegeneration. Similarly, the non-motor complications of PD, especially the gastrointestinal tract (GIT) disturbance increases the disease burden on both the PD patient and caregivers. Different theories have been postulated regarding the mechanisms or pathways involved in PD pathology but gut-brain axis involvement has gained much more momentum. This pathway was first suggested by Braak and colleagues in 2003, where they suggested that PD starts from the GIT before spreading to the brain. However, human exposure to environmental toxicants known to inhibit mitochondrial complex I activity such as rotenone, paraquat and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are well associated with PD. Several reports have shown that oral exposure of laboratory animals to rotenone causes mitochondria dysfunction, GIT disturbance, overexpression of alpha synuclein and microbiota imbalance. This review focuses on the mechanism(s) through which rotenone induces PD pathogenesis and potential for therapeutic small molecules targeting these processes at the earliest stages of the disease. We also focused on the interaction between the GI microbiota and PD pathology.