Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid(DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent ...Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid(DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In nonhuman primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with longstanding deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder(ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies.展开更多
Food must supply a balance of nutrients to support both brain and body.The human brain makes us uniquely human.Essential fatty acids are part of the metabolic pathways that define tissue structure and function.Omega-6...Food must supply a balance of nutrients to support both brain and body.The human brain makes us uniquely human.Essential fatty acids are part of the metabolic pathways that define tissue structure and function.Omega-6(O6)linoleic acid(LA6)has long been known to be required for skin structure,and as a precursor for inflammatory,thrombotic,immune,and other signaling molecules.Omega-3(O3)alpha-linolenic acid(ALA3)and particularly its long chain product docosahexaenoic acid(DHA3)has a key structural role in the brain,retina,and related neural tissue.In the 20 th century western world,inexpensive,high quality oils primarily from LA6-rich/O3-poor vegetable seed oils became dominant fats produced by the food industry.Provision of LA6-rich/O3-poor oils as the sole source of fat in the diets of pregnant animals causes O3 deficiency and poor brain development,primarily because high LA6 antagonizes metabolism of all O3,creating an artificial metabolic demand for O3.Data developed over the last 2~3 decades show that provision of low LA6 combined with preformed DHA3 optimizes brain function.Recent studies emphasize the importance of nutrition to support brain development,with newer findings showing particular importance of fatty acid balance in malnourished children.The World Health Organization(WHO)through the Codex Alimentarius(“Code for Food”)is increasingly recognizing the primacy of brain health and in part on that basis recently acted to recommend balanced fat for Ready-to-Use-Therapeutic Foods used to treat children with severe acute malnutrition.Similar principles are likely to be important in older persons.Industry now has the tools to adjust the composition of oils to support brain health throughout the life cycle.展开更多
基金Supported by NARSAD,Martek Biosciences IncThe Inflammation Research Foundation(IRF)+2 种基金Ortho-Mc Neil Janssen,Astra Zeneca,Eli Lillypreviously a member of the IRF scientific advisory board(Mc Namara RK)the Perinatal Institute at Cincinnati Children’s Hospital(Valentine CJ)
文摘Accumulating translational evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid(DHA) plays a role in the maturation and stability of cortical circuits that are impaired in different recurrent psychiatric disorders. Specifically, rodent and cell culture studies find that DHA preferentially accumulates in synaptic and growth cone membranes and promotes neurite outgrowth, dendritic spine stability, and synaptogenesis. Additional evidence suggests that DHA may play a role in microglia-mediated synaptic pruning, as well as myelin development and resilience. In nonhuman primates n-3 fatty acid insufficiency during perinatal development leads to widespread deficits in functional connectivity in adult frontal cortical networks compared to primates raised on DHA-fortified diet. Preterm delivery in non-human primates and humans is associated with early deficits in cortical DHA accrual. Human preterm birth is associated with longstanding deficits in myelin integrity and cortical circuit connectivity and increased risk for attention deficit/hyperactivity disorder(ADHD), mood, and psychotic disorders. In general, ADHD and mood and psychotic disorders initially emerge during rapid periods of cortical circuit maturation and are characterized by DHA deficits, myelin pathology, and impaired cortical circuit connectivity. Together these associations suggest that early and uncorrected deficits in fetal brain DHA accrual may represent a modifiable risk factor for cortical circuit maturation deficits in psychiatric disorders, and could therefore have significant implications for informing early intervention and prevention strategies.
基金US National Institutes of Health(R01s AT007003,GM103437,GM71534,EY10208,GM49209)Unorthodox Philanthropy+3 种基金Open Philanthropythe Hickey Family Foundationthe Children’s Discovery InstituteWiley Companies。
文摘Food must supply a balance of nutrients to support both brain and body.The human brain makes us uniquely human.Essential fatty acids are part of the metabolic pathways that define tissue structure and function.Omega-6(O6)linoleic acid(LA6)has long been known to be required for skin structure,and as a precursor for inflammatory,thrombotic,immune,and other signaling molecules.Omega-3(O3)alpha-linolenic acid(ALA3)and particularly its long chain product docosahexaenoic acid(DHA3)has a key structural role in the brain,retina,and related neural tissue.In the 20 th century western world,inexpensive,high quality oils primarily from LA6-rich/O3-poor vegetable seed oils became dominant fats produced by the food industry.Provision of LA6-rich/O3-poor oils as the sole source of fat in the diets of pregnant animals causes O3 deficiency and poor brain development,primarily because high LA6 antagonizes metabolism of all O3,creating an artificial metabolic demand for O3.Data developed over the last 2~3 decades show that provision of low LA6 combined with preformed DHA3 optimizes brain function.Recent studies emphasize the importance of nutrition to support brain development,with newer findings showing particular importance of fatty acid balance in malnourished children.The World Health Organization(WHO)through the Codex Alimentarius(“Code for Food”)is increasingly recognizing the primacy of brain health and in part on that basis recently acted to recommend balanced fat for Ready-to-Use-Therapeutic Foods used to treat children with severe acute malnutrition.Similar principles are likely to be important in older persons.Industry now has the tools to adjust the composition of oils to support brain health throughout the life cycle.