Children with neurofibromatosis type 1 (NF1) are increasingly recognized as having a high prevalence of social difficulties and autism spectrum disorders (ASDs). We demonstrated a selective social learning deficit in mice with deletion of a single Nf1 allele (Nf1(+/-)), along with greater activation of the mitogen-activated protein kinase pathway in neurons from the amygdala and frontal cortex, structures that are relevant to social behaviors. The Nf1(+/-) mice showed aberrant amygdala glutamate and GABA neurotransmission, deficits in long-term potentiation and specific disruptions in the expression of two proteins that are associated with glutamate and GABA neurotransmission: a disintegrin and metalloprotease domain 22 (Adam22) and heat shock protein 70 (Hsp70), respectively. All of these amygdala disruptions were normalized by the additional deletion of the p21 protein-activated kinase (Pak1) gene. We also rescued the social behavior deficits in Nf1(+/-) mice with pharmacological blockade of Pak1 directly in the amygdala. These findings provide insights and therapeutic targets for patients with NF1 and ASDs.

Social learning and amygdala disruptions in Nf1 mice are rescued by blocking p21-activated kinase

Differential mechanisms regarding triclosan vs. bisphenol A and fluorene-9-bisphenol induced zebrafish lipid-metabolism disorders by RNA-Seq.

Significance: The precipitous age-related decline in female fertility is intimately associated with a reduction in both the quantity and quality of the germline (oocytes). Although complex etiologies undoubtedly contribute to the deterioration of oocyte quality, increasing attention has focused on the pervasive impact of oxidative stress. Indeed, the prolonged lifespan of the meiotically arrested oocyte places this cell at heightened risk of oxidative lesions, which commonly manifest in dysregulation of protein homeostasis (proteostasis). Although oocytes are able to mitigate this threat via the mobilization of a sophisticated network of surveillance, repair, and proteolytic pathways, these defenses are themselves prone to age-related defects, reducing their capacity to eliminate oxidatively damaged proteins. Recent Advances: Here, we give consideration to the quality control mechanisms identified within the ovary that afford protection to the female germline. Our primary focus is to review recent advances in our understanding of the autophagy pathway and its contribution to promoting oocyte longevity and modulating pathophysiological responses to oxidative stress. In addition, we explore the therapeutic potential of emerging strategies to fortify autophagic activity. Critical Issues: The complex interplay of oxidative stress and autophagy has yet to be fully elucidated within the context of the aging oocyte and surrounding ovarian environment. Future Directions: Emerging evidence provides a strong impetus to resolve the causal link between autophagy and oxidative stress-driven pathologies in the aging oocyte. Such research may ultimately inform novel therapeutic strategies to combat the age-related loss of female fertility via fortification of intrinsic autophagic activity.

Autophagy in Female Fertility: A Role in Oxidative Stress and Aging.

Among the popular animal models of Parkinson’s disease (PD) commonly used in research are those that employ neurotoxins, especially 1-methyl- 4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). This neurotoxin exerts it neurotoxicity by causing a barrage of insults, such as oxidative stress, mitochondrial apoptosis, inflammation, excitotoxicity, and formation of inclusion bodies acting singly and in concert, ultimately leading to dopaminergic neuronal damage in the substantia nigra pars compacta and striatum. The selective neurotoxicity induced by MPTP in the nigrostriatal dopaminergic neurons of the mouse brain has led to new perspectives on PD. For decades, the MPTP-induced mouse model of PD has been the gold standard in PD research even though it does not fully recapitulate PD symptomatology, but it does have the advantages of simplicity, practicability, affordability, and fewer ethical considerations and greater clinical correlation than those of other toxin models of PD. The model has rejuvenated PD research and opened new frontiers in the quest for more novel therapeutic and adjuvant agents for PD. Hence, this review summarizes the role of MPTP in producing Parkinson-like symptoms in mice and the experimental role of the MPTP-induced mouse model. We discussed recent developments of more promising PD therapeutics to enrich our existing knowledge about this neurotoxin using this model.

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Shaozhi Zhang

Papers

Fluorene-9-bisphenol exposure induces cytotoxicity in mouse oocytes and causes ovarian damage.

The effects of fluorene-9-bisphenol on female zebrafish (Danio rerio) reproductive and exploratory behaviors.

Venlafaxine plus melatonin ameliorate reserpine-induced depression-like behavior in zebrafish.

Environmental level of the antidepressant venlafaxine induces behavioral disorders through cortisol in zebrafish larvae (Danio rerio)

Melatonin alleviates the deterioration of oocytes and hormonal disorders from mice subjected to glyphosate.