Screening Of High DHA Producing Algae And The Preventive Effect Of Related Products On Alzheimer’s Disease

Long chain n-3 polyunsaturated fatty acids(n-3 LC PUFAs)are long-chain fatty acids(20 or more carbons)whose first double bond is located after the third carbon at the methyl end.Docosahexaenoic acid(DHA)is a kind of typical long chain n-3polyunsaturated fatty acids with six double bonds,which is not only an essential factor for healthy growth and development of infants,but also can improve cardiovascular health,reduces symptoms of rheumatoid arthritis and depression,and improves cognitive function.With the continuous improvement of people’s living standard and medical level,human life expectancy is increasing,and the global aging trend is becoming more and more obvious.Cognitive decline,however,begins to seriously affect normal life in the elderly,where Alzheimer’s disease has the most widespread impact.The etiology of AD is very complex,so it is still inconclusive in academia.Because DHA is important in cognitive ability and nervous system development,many scholars have begun to actively consider whether it has a positive effect on AD.In this study,we will attempt to use magnetic resonance imaging(MRI)technology to analyze the structural changes of the brain in AD-related transgenic mice,so as to explain the possible mechanism of DHA from another perspective.Schizochytrium sp.has been widely industrialized as a high DHA producing algae recognized worldwide.In order to obtain suitable DHA material for mouse feeding,the original Schizophyllum sp.isolated from seawater was used to obtain a high DHA-producing strain by plasma beam injection mutagenesis.The DHA yield was increased by 44% and the net DHA content was increased by 23% compared with the original strain.Then,the fermentation medium was optimized by adjusting nitrogen source,carbon source,microelements and p H value.The fermentation process was optimized by adjusting the parameters such as inoculum amount,incubation temperature,tank pressure,dissolved oxygen,and feeding.Finally,the DHA yield was further increased by 18% and the net DHA content was further increased by 8%.In order to obtain the more pure DHA algal oil,a series of oil refining process studies were carried out,including: solvent free extraction,alkali refining,bleaching and deodorization.The DHA algal oil with 50.2% DHA content,0.01 mmol/kg peroxide value,0.15 mg KOH/g acid value with good sensory and stability was obtained through the optimization of anti-oxidation formula.However,DHA algal oil is easily oxidized and insoluble in water,it is not suitable for direct feeding in mice.Therefore,the research work of DHA algal oil microcapsules was continued.By comparing the spray drying process,spray freeze-drying process,coating process and granulation process,it was found that the coating process had the best performance.After 6 months of accelerated test at 37℃,the DHA content loss of the microcapsules prepared by the coating process was less than 5%,the peroxide value was less than10%,and the sensory was the best.Finally,the DHA microcapsule samples were used to prepare a mouse diet suitable for this study.3-month-old APP/PS1 double transgenic mice were fed with DHA mixed feeds for 4 months to assess the effects of DHA on cognitive ability in AD mice through the Morris water maze and open field tests.Compared to AD mice,escape latency significantly decreased on the fifth day while target quadrant stay time,and the crossing number of platforms increased by varying degrees after DHA feeding.Brain tissue section staining revealed that DHA significantly reduced Aβ and nerve fibers tangles in the brain of AD mice.Then,the brain of AD mice was dissected,and the metabolites in different brain regions were extracted and analyzed.The results showed that DHA had a certain positive regulatory effect on glycine,glutamate,and aspartate.Finally,resting-state f MRI was used to scan different brain regions in vivo,and it was found that DHA could enhance the functional connectivity between the temporal lobe association cortex,somatosensory cortex and motor cortex and the hippocampus,which explained the improvement effect of DHA on AD from a new perspective.In summary,the DHA yield and net DHA content were increased by 70% and32%,respectively,through the mutagenesis performed by plasma beam injection in wild Schizophyllum sp.and the optimization of fermentation process and formula.DHA microcapsules with good sensory and stability were obtained through extraction,refining,and microencapsulation.Finally,the efficacy of the diet prepared with this microcapsule on AD mice was studied,and it was found that DHA could reduce Aβand NFT in AD mice.Moreover,through f MRI,it was found for the first time that DHA could improve the behavioral performance by improving the connectivity function of different brain regions,which revealed the possible mechanism of DHA in the prevention of AD from another side.