Apigenin attenuates depressive-like behavior via modulating monoamine oxidase A enzyme activity in chronically stressed mice.

Chronic stress is a risk factor for depression and is characterized by elevated levels of brain monoamine oxidase A (MAOA). Mounting evidence has shown that MAOA is a biochemical link between stress and depression. Apigenin (API), a natural flavonoid, as demonstrated in vitro inhibitory effect on MAOA, is suggestive of antidepressant-like activity. However, the in vivo inhibitory effect of API on MAOA and how it affects depression still remain unclear. Here, we report the probable mechanisms of action of API in chronic unpredictable mild stress (CUMS)-induced depression in mice. Treatment with API reversed anhedonia, and reduced anxiety and immobility time in behavioral studies. API reduced brain corticosterone and malondialdehyde (MDA) levels but increased brain levels of glutathione and superoxide dismutase. Furthermore, interleukin-6 and tumor necrosis factor-α were attenuated by API. It also restored cell loss and inhibited the activity of MAOA in the hippocampal brain regions and prefrontal cortex. Comparative binding affinity of API for MAOA (-7.7 kcal/mol) through molecular docking studies was greater than that of reference compound, clorgyline (-6.8 kcal/mol). Favorable hydrophobic interactions important to API binding at MAOA binding cavity was revealed to include conventional hydrogen bond (Cys323 and Tyr444), π-Sulfur (Cys323), π-π Stacked (Tyr407), π-π T-shaped (Phe208), π-lone pair and π-alkyl (Ile335, Ile180) interactions. These results suggest that API is a potent, selective, reversible inhibitor of MAOA with capability of attenuating CUMS-induced depression via inhibiting MAOA enzyme activity and altering other pathomechanisms.

Neural stem cell research in Africa: current realities and future prospects.

Neural stem cells (NSCs) are immature progenitor cells that are found in developing and adult brains that have the potential of dividing actively and renewing themselves, with a complex form of gene expression. The generation of new brain cells in adult individuals was initially considered impossible, however, the landmark discovery of human neural stem cells in the hippocampus has been followed by further discoveries in other discreet regions of the brain. Investigation into the current state in Africa of the research and use of NSCs shows relatively limited activities on the continent. Information on the African application of NSCs for modelling disease mechanisms, drug discovery, and therapeutics is still limited. The International Brain Research Organization (IBRO)-African Regional Committee (ARC), with support from the Company of Biologists, and the Movement Disorder Society, sponsored the first African Basic School on NSC in Ibadan, Nigeria, with the vision of bringing together young neuroscientists and physicians across different fields in neuroscience to learn from leaders who have applied NSCs in stem cell research, the pathophysiology of neurodegenerative diseases, neuroanatomy, and neurotherapeutics. Twenty early-career researchers in academic institutions at junior and senior faculty cadres were selected from South Africa, Uganda and Nigeria. The students and organizer of the school, who wrote this review on the state of NSCs research in Africa, recommended the following: (1) other African countries can take a cue from South Africa and Nigeria in probing the phenomena of adult neurogenesis in unique animal species on the continent; (2) Africa should leverage the expertise and facilities of South African scientists and international collaborators in scaling up NSC research into these unique species and (3) Centers of Excellence should be established on the continent to serve as research hubs for training postgraduate students, and facilities for African scientists who trained overseas on NSCs.

Quercetin mitigates scopolamine-induced memory dysfunction: impact on oxidative stress and cholinergic mechanisms.

Despite the promising neuroprotective activities of quercetin (QT), its' effect on cholinergic neurotransmission needs further elucidation. In this study, we explored the impact of QT on oxidative stress and cholinergic neurotransmission with emphasis on the possible involvement of choline acetyltransferase (ChAT) as a potential mechanism of QT on memory function at the hippocampal sub-regions and prefrontal cortex of mice brains. Mice were administered orally with QT (12.5 and 25 mg/kg) alone or in combination with SC (3 mg/kg, intraperitoneally) once daily for seven consecutive days. Thirty minutes after the last treatment, memory function was assessed using the Y-maze test. Levels of biomarkers of oxidative stress and acetylcholinesterase (AChE) activity were determined using a microplate reader. ChAT activity was determined by immunohistochemistry. QT pretreatment enhanced memory performance and reversed scopolamine (SC)-induced memory impairment in the Y-maze test. QT also reduced malondialdehyde and nitrite levels in mice brains. Glutathione levels were increased in mice brains as a result of QT administration. Levels of antioxidant enzymes (superoxide dismutase and catalase) were significantly increased in the mice brains, but AChE activity was reduced by QT. The activity of ChAT was significantly enhanced by QT in the hippocampal sub-regions and the prefrontal cortex of the mice brains. This study has shown that QT mitigated SC-induced memory dysfunction by inhibiting oxidative stress and AChE activity. Also, QT enhanced ChAT activity, particularly in the hippocampal sub-regions and the prefrontal cortex. These mechanisms, may be possible means through which QT improves memory performance.