Abstract
Repeated mild traumatic brain injury (rmTBI) poses adversity in the form of neurological deficits. The ignition of long-term neurological aberrations post-TBI is appended with the microbiota gut–brain axis perturbation. Herein, we examined whether quercetin, which is anti-inflammatory and antioxidant flavonoid, serves as a prebiotic and modifies the compromised microbiome gut–brain axis in rmTBI mouse model. Male C57BL/6 mice were subjected to rmTBI for 7 times. The quercetin (50 mg/kg) was administered peroral from the day1 of first injury till 7 days post-injury. The neurobehavioral assessments were performed using return of righting reflex (ROR), rotarod, forced swimming test (FST), elevated zero maze (EZM), novel object recognition test (NORT), and Y-maze. Mice fecal samples, brains, and intestines were collected for molecular studies. Mice underwent rmTBI showed significant neurological deficits in ROR and rotarod test and also exhibited long-term neuropsychiatric aberrations like anxiety- and depression-like phenotypes, and cognitive deficits in EZM, FST, and Y-maze assays, respectively. Repeated peroral administration of quercetin ameliorated these neuropsychiatric problems. Quercetin treatment also restored the increased expression of GFAP and decreased expression of occludin and doublecortin in the frontal cortex and hippocampus of rmTBI mice. The altered levels of acetate and propionate, and microbial phylum abundance in fecal samples were also normalized in the quercetin-treated group. We also noted an improved intestinal permeability indicated by reduced villi rupture, blunting, and mucosal thinning in quercetin-treated mice. We suggest that the neuroprotective effect of quercetin may be mediated via remodeling of the microbiome gut–brain axis in rmTBI mouse model.
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The authors (RB, MRB, TP, NS, LV, SG, and MPD) would like to thank NIPER, Hyderabad, for providing all the resources and DoP, Ministry of Chemicals and Fertilizers, Government of India, for providing fellowship.
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MPD thanks funding from the DST-SERB, File number SRG/2020/002439.
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RB executed behavioral studies and prepared the manuscript draft; MRB assisted in molecular studies and making a manuscript draft; TP and NS assisted in behavioral studies and animals sacrifice; LV and SG helped in SCFAs estimation; and MPD contributed to study design, data interpretation, and manuscript edits.
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Balasubramanian, R., Bazaz, M.R., Pasam, T. et al. Involvement of Microbiome Gut–Brain Axis in Neuroprotective Effect of Quercetin in Mouse Model of Repeated Mild Traumatic Brain Injury. Neuromol Med 25, 242–254 (2023). https://doi.org/10.1007/s12017-022-08732-z
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DOI: https://doi.org/10.1007/s12017-022-08732-z