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Prenatal stress (PS) significantly influences the neurodevelopment of offsprings, potentially resulting in deficits in learning and memory. Mangiferin (MGF) is a naturally occurring flavonoid compound found in many plants, exhibits various pharmacological effects. The study investigates the potential molecular mechanisms of MGF in improving learning and memory deficits in offspring exposed to PS. Animal model of PS offspring and ACR-induced PC12 cell model were used to investigate the effects of MGF. Synaptic plasticity-related proteins and the BDNF signaling pathway were studied, as well as MGF's potential to alleviate endoplasmic reticulum stress (ERS). MGF can mitigate learning and memory impairments and enhance the density of hippocampal neurons, as well as increase the expression of neuronal markers Neurogranin (Ng), DLG4 and activity marker c-fos in the offspring of PS mice. Meanwhile, MGF significantly increased BDNF signaling pathway and synaptic plasticity-related proteins in PS offspring. MGF also efficiently alleviated ERS. Additionally, MGF significantly up-regulated the reduced viability, DLG4 protein expression and synaptic plasticity-related proteins in ACR-induced PC12 cells. MGF can improve endoplasmic reticulum morphology and down regulated the expression of key molecular proteins in the endoplasmic reticulum signaling pathway. MGF could improve the cognitive and memory impairments in the PS offspring mice. The underlying mechanisms involved the alleviation of ERS and improvement of synaptic plasticity-related proteins. The study indicated that MGF holds promise as an effective intervention for ameliorating learning and memory deficits associated with PS, and it offers potential therapeutic effect for neurological disorders linked to ACR dysfunction. Show less

Prenatal stress may lead to cognitive and behavioral dysfunction in the offspring. Large evidence has shown the deleterious effects of maternal stress on cognitive and behavioral functions of the offspring; however, the effect of paternal stress has not been well documented. In the present study, we aimed to investigate the effect of paternal stress (chronic electrical footshocks, post-traumatic stress disorder or PTSD-like model) on cognitive and behavioral functions, and brain-derived neurotrophic factor (BDNF) hippocampal level in both male and female offspring during adolescence. The father rat (stress-exposed) was exposed to three consecutive shocks in a fear conditioning apparatus for ten times during four weeks, in an uncertain and unpredictable schedule. Saline (0.5 mL) or lithium chloride (50 mg/kg) was intraperitoneally injected to male and female offspring during 21-41 postnatal day (PND). The results showed that paternal stress decreased locomotor activity in female offspring, and increased anxiety-like behavior in both male and female offspring, with more effect on females. Paternal stress also decreased pain subthreshold only in female offspring and impaired passive avoidance and spatial memory in both male and female offspring. Paternal stress also decreased BDNF expression level only in female offspring. However, lithium reversed most of the behavioral dysfunctions in rats' offspring with a history of paternal stress. We concluded that paternal stress significantly impairs cognitive and behavioral function in the offspring during adolescence, with more effect on females. Also, chronic lithium treatment may reverse the deleterious effects of paternal stress. Show less

Prenatal stress is a significant risk factor that can lead to neurobehavioral deficits in offspring. In the present study, we examined the effects of a probiotic mixture on anxiety, memory, and underlying possible molecular pathways in prenatally stressed rats. Male offspring exposed to chronic unpredictable stress (CUS) during fetal life were received either saline (CUS+SAL) or a probiotic mixture (CUS+PRO) for 30 days post-weaning. Non-stressed controls were also given either saline (CON+SAL) or probiotics (CON+PRO). The passive avoidance test and the elevated zero maze test were used to assess avoidance memory and anxiety-like behavior, respectively. In comparison to the CON+SAL controls, the CUS+SAL group exhibited significant anxiety-like behavior and impaired avoidance memory. At a molecular level, the behavioral impairments were accompanied by increased serum levels of the oxidant, MDA, and decreased serum levels of antioxidants, TAC, GSH, and SOD, upregulation of the hippocampal serotonin receptor Htr1a gene, while downregulation of microRNAs miR-26a and miR-320-3p, reduced BDNF, and increased Bax/Bcl-2 ratio apoptosis in the duodenum. Probiotics effectively mitigated these alterations. The intervention improved behavioral functions, normalized oxidative and antioxidative stress markers, and restored the expression of Htr1a and miR-320-3p to near-normal levels, while miR-26a expression remained unaffected by the treatment. It also enhanced the Bax/Bcl-2 ratio and increased BDNF content. Interestingly, unstressed control rats were unresponsive to the probiotic treatment. Conclusively, probiotic supplementation sufficiently alleviates the adverse effects of fetal life stress, possibly by affecting the gut-brain axis, highlighting the importance of beneficial bacteria in neurobehavioral development and maintenance. Show less