Yuxi Jia,Ping Li,Fei Wu,Fanjie Zeng,Beilin Zhang,Jinpeng Wang
Background: In clinic, valproic acid (VPA) has been widely used in the treatments of epilepsy and is currently under clinical trials for the treatments of multiple diseases. However, gravidas receiving VPA treatment during their early stage of pregnancy were reported to be associated with elevated incidences of autism in their child. In this study, the potential influences of n-3/n-6 polyunsaturated fatty acids (PUFAs) as supplements were investigated in VPA-induced autistic rat model.Materials and Methods: A rat model of autism spectrum disorder (ASD) was established by VPA exposure at the E12.5 day of gestation. Neonatal male Wistar rats (n = 24) were divided into VPA group, A group and B group, while normal neonatal male Wistar rats served as controls. At P21 days, animals in the control and VPA groups were fed with standard chow, while rats in the A group were fed with n-3 PUFA free chow, and those in the B group with n-3/n-6 PUFA (1:5) chow. The duration of the diet was from P21 days to 3 months. All rats were subjected to the examinations of repetitive stereotyped behaviors and changes in social interaction at the end of supplement. The neuroinflammation in the brain and serum was also evaluated. Hematoxylin–eosin (HE) staining and Nissl staining were used to observe the neuronal injury in hippocampus.Results: In the B group, the repetitive stereotyped behaviors reduced, the social communication was improved, the neuronal loss and proinflammatory cytokines in the hippocampus reduced, and the extracellular STAT3 activation was inhibited in the hippocampus, as compared to the B group.Conclusion: Supplements with n-3/n-6 PUFA (1:5) rescues repetitive stereotyped behaviors and social deficits in neonatal rats exposed to VPA, likely due to the improved inflammatory responses through the alteration of STAT3 signaling. This study provides evidence for the use of n-3/n-6 PUF in the treatment of autism in humans.
Polyunsaturated fatty acids (PUFA), a group of nourishing and health-promoting nutrients, ameliorate age-related chronic diseases. However, how PUFA especially n-3 PUFA exert anti-aging functions remains poorly understood. Here we link fish oil, docosahexaenoic acid (DHA) and arachidonic acid (AA) to the aging etiology via a redox-telomere-antioncogene axis based on D-galactose-induced aging mice. Both fish oil and PUFA enhanced hepatic superoxide dismutase (SOD) and catalase activities and cardiac SOD activities within the range of 18%-46%, 26%-65% and 19%-58%, respectively, whereas reduced cerebral monoamine oxidase activity, plasma F 2 -isoprostane level and cerebral lipid peroxidation level by 56%-90%, 20%-79% and 16%-54%, respectively. Thus, PUFA improve the in vivo redox and oxidative stress induced aging process, which however does not exhibit a dose-dependent manner. Notably, both PUFA and fish oil effectively inactivated testicular telomerase and inhibited c-Myc -mediated telomerase reverse transcriptase expression, whereas n-3 PUFA rather than n-6 PUFA protected liver and testes against telomere shortening within the range of 13%-25% and 25%-27%, respectively. Therefore, n-3 PUFA may be better at inhibiting the DNA damage induced aging process. Surprisingly, only DHA significantly suppressed cellular senescence pathway evidenced by testicular antioncogene p16 and p53 expression. This work provides evident support for the crosstalk between PUFA especially n-3 PUFA and the aging process via maintaining the in vivo redox homeostasis, rescuing age-related telomere attrition and down-regulating the antioncogene expression.
危险品化学品经营许可证（带存储）