RESUMO
Monosodium glutamate (MSG) is one of the most widely used food additives. However, it has been linked to protein malnutrition (PM) and various forms of toxicities such as metabolic disorders and neurotoxic effects. The current study is the first to explore the association between MSG, PM, and induced brain injury similar to attention-deficit/hyperactivity disorder (ADHD). Moreover, we determined the underlying mechanistic protective pathways of morin hydrate (MH)-a natural flavonoid with reported multiple therapeutic properties. PM was induced by feeding animals with a low protein diet and confirmed by low serum albumin measurement. Subsequently, rat pups were randomized into seven groups of 10 rats each. Group I, III, and VI were normally fed (NF) and groups II, IV, V, and VII were PM fed. Group I served as normal control NF while Group II served as PM control animals. Group III received NF + 0.4 g/kg MSG, Group IV: PM + 0.4 g/kg MSG, Group V: PM + 60 mg/kg MH, Group VI: NF + 0.4 kg/g MSG + 60 mg/kg MH and Group VII: PM + 0.4 kg/kg MSG + 60 mg/kg MH. At the end of the experimental period, animals were subjected to behavioral and biochemical tests. Our results showed that treatment of rats with a combination of MSG + PM-fed exhibited inferior outcomes as evidenced by deteriorated effects on behavioral, neurochemical, and histopathological analyses when compared to rats who had received MSG or PM alone. Interestingly, MH improved animals' behavior, increased brain monoamines, brain-derived neuroprotective factor (BDNF), antioxidant status and protein expression of Nrf2/HO-1. This also was accompanied by a significant decrease in brain MDA, inflammatory markers (NF-kB, TNF-α and IL1ß), and suppression of TLR4/NLRP3/caspase-1 axis. Taken together, MSG and/or PM are associated with neuronal dysfunction. Our findings suggest MH as a potential neuroprotective agent against brain insults via targeting Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome signaling pathways.
RESUMO
Oxytocin (OXT) -"the love hormone"- has been involved in the anti-depressant activity of some selective serotonin reuptake inhibitors (SSRIs). The exact mechanism underlying the OXT pathway in depression is not fully clear. This study aimed to investigate the effect of OXT analogue, carbetocin (CBT) and the SSRI, escitalopram (ESCIT) on depressive-like behaviors following maternal separation (MS). It is worthy to mention that intranasal CBT has been approved by U.S. Food and Drug Administration (FDA) for Prader-Willi syndrome. Adolescent Wistar albino maternally-separated rats were given CBT, (100 µg/animal/d via inhalation route), and, ESCIT, (20 mg kg-1, per os ( p.o.)) either alone or in combination for 7 d. Repeated 3-h MS demonstrated increased immobility time in forced swim test (FST) and decreased locomotor activity in open field test. MS elevated plasma level of adrenocortico-trophic hormone (ACTH) but notably reduced plasma OXT, with no effect on hippocampal OXT-R expression. Following MS, hippocampal contents of 5-hydroxytryptamine receptors (5HT1A-R), serotonin transporter (SERT) were increased. CBT and ESCIT corrected the behavioral dysfunction in FST and suppressed the high levels of ACTH. Additionally, both treatments boosted OXT level, reduced 5HT1A-R and normalized SERT contents, which reflects increased availability of serotonin. Finally, CBT markedly ameliorated the histopathological damage induced by MS and suppressed the increased glial fibrillary acidic protein. CBT and ESCIT manage depressive-like behavior by positively affecting serotonergic and oxytocinergic systems. Targeting OXT system -using CBT- ameliorated depressive like behaviors induced by maternal separation most probably via enhancing OXT plasma levels, attenuating hormonal ACTH and restoring the expression of hippocampal oxytocin and serotonin mechanisms.
