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Item Induction of aggression and anxiety-like responses by perfluorooctanoic acid is accompanied by modulation of cholinergic- and purinergic signaling-related parameters in adult zebrafish(Elsevier Inc., 2022) Adedara, I. A. || || || || || || || || || || ||; Souza, T. P.; Canzian, J.; Olabiyi, A. A.; Borba, J. V.; Biasuz, E.; Sabadin, G. R.; Goncalves, F. L. S.; Costa, F. V.; Schetinger, M. R. C.; Farombi E.O.; Rosemberg, D. B.Perfluorooctanoic acid (PFOA) is a contaminant of global concern owing to its prevalent occurrence in aquatic and terrestrial environments with potential hazardous impact on living organisms. Here, we investigated the influence of realistic environmental concentrations of PFOA (0, 0.25, 0.5, or 1.0 mg/L) on relevant behaviors of adult zebrafish (Danio rerio) (e.g., exploration to novelty, social preference, and aggression) and the possible role of PFOA in modulating cholinergic and purinergic signaling in the brain after exposure for 7 consecutive days. PFOA significantly increased geotaxis as well as reduced vertical exploration (a behavioral endpoint for anxiety), and increased the frequency and duration of aggressive episodes without affecting their social preference. Exposure to PFOA did not affect ADP hydrolysis, whereas ATP and AMP hydrolysis were significantly increased at the highest concentration tested. However, AChE activity was markedly decreased in all PFOA-exposed groups when compared with control. In conclusion, PFOA induces aggression and anxiety-like behavior in adult zebrafish and modulates both cholinergic and purinergic signaling biomarkers. These novel data can provide valuable insights into possible health threats related to human activities, demonstrating the utility of adult zebrafish to elucidate how PFOA affects neurobehavioral responses in aquatic organisms.Item Indole-3-propionic acid mitigates chlorpyrifos-mediated neurotoxicity by modulating cholinergic and redox-regulatory systems, inflammatory stress, apoptotic responses and DNA damage in rats(Elsevier B.V., 2022) Owumi, S. E.; Adedara, I. A.; Oyelere, A. K.This study probed the neuroprotective influence of indole-3-propionic acid (IPA) in rats exposed to chlorpyrifos (CPF) alone at 5 mg/kg body weight or co-administered with IPA at 12.5 and 25 mg/kg for 14 days. Behavioral data indicated that IPA significantly (p < 0.05) abated CPF-mediated anxiogenic-like behaviors with concomitant improvement in the locomotor and exploratory behaviors as substantiated by track plots and heat maps data. Also, IPA mitigated CPF-mediated diminution in cholinergic and antioxidant defense systems whereas it mark- edly improved thioredoxin level and thioredoxin reductase activity in cerebral and cerebellar tissues of the animals. Co-administration of IPA significantly enhanced anti-inflammatory cytokine, interleukin-10 but sup- pressed oxidative and inflammatory stress, caspase-9 and caspase-3 activation with concomitant reduction in 8- hydroxy-2'-deoxyguanosine (8-OHdG) level and histological damage. Collectively, IPA-mediated neuro- protection involves modulation of cholinergic and redox-regulatory systems, inflammatory stress, apoptotic re- sponses and DNA damage in cerebrum and cerebellum of rats.Item Chronic ciprofloxacin and atrazine co-exposure aggravates locomotor and exploratory deficits in non-target detritivore speckled cockroach (Nauphoeta cinerea)(Springer-Verlag GmbH, 2021) Adedara, I. A. || || || || || || ||; Godswill, U. S.; Mike. M. A.; Afolabi, B. A.; Amorha, C. C.; Sule, J.; Rocha, J. B. T.; Farombi, E. O.The global detection of ciprofloxacin and atrazine in soil is linked to intensive anthropogenic activities in agriculture and inadvertent discharge of industrial wastes to the environment. Nauphoeta cinerea is a terrestrial insect with cosmopolitan distribution and great environmental function. The current study probed the neurobehavioral and cellular responses of N. cinerea singly and jointly exposed to atrazine (1.0 and 0.5 μg g−1 feed) and ciprofloxacin (0.5 and 0.25 μg g−1 feed) for 63 days. Results demonstrated that the reductions in the body rotation, maximum speed, turn angle, path efficiency, distance traveled, episodes, and time of mobility induced by atrazine or ciprofloxacin per se was exacerbated in the co-exposure group. The altered exploratory and locomotor in insects singly and jointly exposed to ciprofloxacin and atrazine were verified by track plots and heat maps. Furthermore, we observed a decrease in acetylcholinesterase and anti-oxidative enzyme activities with concomitant elevation in the levels of lipid peroxidation, nitric oxide, and reactive oxygen and nitrogen species were significantly intensified in the midgut, hemolymph, and head of insects co-exposed to ciprofloxacin and atrazine. In conclusion, exposure to binary mixtures of ciprofloxacin and atrazine elicited greater locomotor and exploratory deficits than upon exposure to the individual compound by inhibiting acetylcholinesterase activity and induction of oxido-inflammatory stress responses in the insects. N. cinerea may be a usable model insect for checking contaminants of ecological risks.Item Kolaviron via anti-inflammatory and redox regulatory mechanisms abates multi-walled carbon nanotubes-induced neurobehavioral deficits in rats(Springer-Verlag GmbH, 2020) Adedara, I. A.; Awogbindin, I. O.; Owoeye, O.; Maduako, I. C.; Ajeleti, A. O.; Owumi, S. E.; Patlola, A. K.; Farombi, E. O.Exposure to multi-walled carbon nanotubes (MWCNTs) reportedly elicits neurotoxic effects. Kolaviron is a phytochem- ical with several pharmacological effects namely anti-oxidant, anti-inflammatory, and anti-genotoxic activities. The present study evaluated the neuroprotective mechanism of kolaviron in rats intraperitoneally injected with MWCNTs alone at 1 mg/kg body weight or orally co-administered with kolaviron at 50 and 100 mg/kg body weight for 15 consecutive days. Following exposure, neurobehavioral analysis using video-tracking software during trial in a novel environment indicated that co-administration of both doses of kolaviron significantly (p < 0.05) enhanced the locomotor, motor, and exploratory activities namely total distance traveled, maximum speed, total time mobile, mobile episode, path efficiency, body rotation, absolute turn angle, and negative geotaxis when compared with rats exposed to MWCNTs alone. Further, kolaviron markedly abated the decrease in the acetylcholinesterase activity and antioxidant defense system as well as the increase in oxidative stress and inflammatory biomarkers induced by MWCNT exposure in the cerebrum, cerebellum, and mid-brain of rats. The amelioration of MWCNT-induced neuronal degeneration in the brain structures by kolaviron was verified by histological and morphometrical analyses. Taken together, kolaviron abated MWCNT-induced neurotoxicity via anti-inflammatory and redox regulatory mechanisms.Item Nigral and ventral tegmental area lesioning induces testicular and sperm morphological abnormalities in a rotenone model of Parkinson’s disease(Elsevier B.V., 2020) Awogbindin, I. O.; Adedara, I. A.; Adeniyi, P. A.; Agedaha, A. E.; Oyetunde, B. F.; Olorunkalu, P. D.; Ogbuewua, E.; Akindoyeni, I. A.; Mustapha, Y. E.; Ezekiel, O. G.; Farombi, E. O.Although sexual health is affected by Parkinson’s disease (PD), the effect on testicular health and/or sperm quality is not well discussed. After 21 days of rotenone lesioning, we observed dopaminergic neuronal degeneration in the substantia nigra and hypothalamus. There were minimal SPACA-1-expressing epididymal spermatozoa with morphological abnormalities, scanty luminal spermatozoa and reduced testicular spermatids and post-meiotic germ cells indicating hypospermatogenesis. Occludin-expressing sertoli cells were dispersed over a wide area indicating compromised blood-testes barrier. Activated caspase-3 expression was intense while immunoreactivity of spermatogenic-enhancing SRY and GADD45 g was weak. Although serum follicle stimulating hormone level was not affected, the lesion was associated with reduced serum testosterone level, testicular oxidative damage and inhibition of acetylcholinesterase activity, even when rotenone was not detected in the testes. Together, dopaminergic lesions may mediate testicular and sperm abnormalities via the brain-hypothalamic- testicular circuit independent of the pituitary, thereby establishing a causal link between Parkinsonism and reproductive dysfunction.Item Neuroprotective mechanisms of selenium against arsenic-induced behavioral impairments in rats(Elsevier B.V., 2020) Adedara, I. A.; Fabunmi, A. T.; Ayenitaju, A. C.; Atanda, O. E.; Adebowale, A. A.; Ajayi, B. O.; Rocha, J. B. T.; Owoeye, O.; Farombi, E. O.Environmental pollution due to arsenic is associated with several adverse health effects including neurotoxicity in animals and humans. Selenium is a nutritionally essential trace metalloid well documented to elicit com- pelling pharmacological activities in vitro and in vivo. Report on the influence of selenium on arsenic-mediated behavioral derangement is lacking in literature. Hence, to fill this knowledge gap, rats were either exposed to arsenic per se in drinking water at 60 pg AsO2Na/L or co-administered with inorganic selenium at 0.25 mg/kg or organic selenium diphenyl diselenide (DPDS) at 2.5 mg/kg body weight for 45 successive days. Neurobehavioural data from rats in a new environment using video-tracking software evinced that inorganic and organic forms of selenium significantly (p < 0.05) abrogated arsenic-induced motor and locomotor in- sufficiencies such as increased negative geotaxis and fecal pellets numbers as well as the diminution in grip strength, body rotation, maximum speed, absolute turn angle and total distance travelled. The augmentation in the behavioral activities in rats co-administered with arsenic and both forms of selenium was substantiated using track and occupancy plots analyses. Selenium mitigated arsenic-induced decreases in glutathione level and acetylcholinesterase activity as well as the increase in oxidative stress and reactive oxygen and nitrogen species. Moreover, selenium diminished inflammatory parameters (myeloperoxidase activity, nitric oxide, tumour ne- crosis factor alpha and interleukin-1 beta levels), caspase-3 activity and ameliorated histological lesions in the cerebellum, cerebrum and liver of the rats. Collectively, selenium abated arsenic-induced behavioral derange- ments via anti-inflammation, antioxidant and anti-apoptotic mechanisms in rats.