| Ethanol exposure in the developing brain can cause a series of central nervous development damage,and Fetal Alcohol Spectrum Disorder(FASD)may occur.Ethanol exposure has a variety of effects on the developing central nervous system,including affecting brain volume,damaging the development of brain such as hippocampus,cortex and cerebellum,causing oxidative stress injury and inflammation,causing extensive abnormal death of neurone,and exerts important effects on cognition and memory.Chitooligosaccharide(COS)was a natural basic amino oligosaccharide.It attracted wide attention because of its water solubility,easy degradation and minimal cytotoxicity.Many literatures have shown that COS has a variety of physiological activities,such as antioxidant,anti-inflammatory,immunomodulatory and neuroprotective activities.COS has a good ability to penetrate the blood-brain barrier and can reach the brain directly.In this study,the alleviating effect of COS on alcohol-induced nerve injury in neonatal rats was investigated to provide a theoretical basis for the further development and utilization of the neuroprotective activity of COS.The main research contents and results of this study are as follows:(1)FASD model was established by administering alcohol to newborn SD rats on the 5th to 9th day after birth,COS intervention and docosahexaenoic acid intervention were performed respectively before alcohol exposure,and behavioral experiment was performed on the 21 st to 26 th day after birth.By measuring the body and brain weight and behavioral data of the newborn rats during ethanol exposure,and carrying out the histopathological examination of brain tissue of neonatal rats,the growth and development of newborn rats,the changes of brain development and morphology,as well as the status of learning and memory ability were analyzed.The results showed that COS could alleviate the slow weight gain of neonatal rats induced by alcohol exposure and reduce the damage on brain development.To improve the apoptosis and degeneration of neurone in the hippocampus and cortical region of neonatal rats induced by alcohol.In addition,the escape latency in the Morris water maze was reduced,the residence time in the target quadrant was increased,and the number of crossing the target platform was increased.In addition,the memory and cognitive impairments induced by alcohol exposure in neonatal rats were improved.(2)Interventional effects of COS on Brain derived neurotrophic factor(BDNF)and neurotransmitter abnormalities induced by alcohol exposure were studied in neonatal rat model of FASD.By measuring the changes of BDNF,Acetycholine(A-Ch)and acetylcholinesterase(A-ch E)in brain tissue of neonatal rats,the developmental environment of central nervous system and the metabolism of neurotransmitters in rats were analyzed.The results showed that COS could alleviate the decrease of BDNF content induced by alcohol exposure,inhibit the decrease of A-Ch and the increase of A-ch E in the brain tissue of neonatal rats induced by alcohol exposure,and maintain the normal transmission of nerve signals.(3)The intervention effect of COS on oxidative stress injury induced by alcohol exposure in FASD model was studied.The levels of Glutathione(GSH),Malondialdehyde(MDA),Superoxide dismutase(SOD)activity and Catalase(CAT)in brain tissue were determined,Total antioxidant capacity(T-AOC)and proteine xpression of Nrf2(NF-E2-related factor 2)and m RNA expression of P53 and JNK were used to observe the oxidative damage of neonatal rats.The results showed that COS could increase the level of GSH and decrease the content of MDA in the brain of neonatal rats,and increased the activity of SOD,CAT and T-AOC,inhibited the expression of P53 and JNK at m RNA levels,significantly increased the protein expression of Nrf2,and alleviated the oxidative damage in the brain tissue of neonatal rats caused by alcohol exposure.This study indicated that COS may inhibit oxidative stress caused by alcohol exposure by inhibiting the expressions of P53 and JNK and increasing the expression of Nrf2,and alleviate the apoptosis of neurone in the developing brain.(4)The intervention effect and mechanism of COS on alcohol-induced inflammatory injury in neonatal rat model of FASD were studied.By measuring the changes in the levels of inflammatory factors and the expression of inflammatory mediators in neonatal rats after COS intervention,the regulatory effect of COS on alcohol-induced inflammatory injury in neonatal rat brain tissue was explored.The results showed that COS could decrease the levels of interleukin-6(IL-6),Tumor necrosis factor-alpha(TNF-α)and increase the level of IL-10 in brain tissues.In addition,COS can down-regulate the m RNA level of IL-1β,IL-4,IL-5,cyclooxygenase(COX-2)and inducible nitric oxide synthase(i NOS)to alleviate the brain inflammation of neonatal rats.(5)In the FASD model,COS inhibited neurone apoptosis by affecting the activation of inherent alcohol-induced neurone apoptosis pathway.The results showed that COS could effectively inhibit the activation of gamma-aminobutyric acid receptor(GABAR)and improve the expression of N-methyl-D-aspartate receptor(NMDAR).In addition,COS inhibited Cleaved Caspase-3 and Caspase-3 expression,and inhibited activation of Bax expression and down-regulation of Bcl /2.The results indicated that COS could alleviate the brain neurone apoptosis and memory and cognitive impairment of neonatal rats induced by alcohol exposure by regulating GABAR,NMDAR and Bcl/2-Bax-Caspase-3 signaling pathways. |
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