title: Omega-3 fatty acid deficiency during brain maturation reduces neuronal and behavioral plasticity in adulthood.
abstract: Omega-3-fatty acid DHA is a structural component of brain plasma membranes, thereby crucial for neuronal signaling; however, the brain is inefficient at synthesizing DHA. We have asked how levels of dietary n-3 fatty acids during brain growth would affect brain function and plasticity during adult life. Pregnant rats and their male offspring were fed an n-3 adequate diet or n-3 deficient diets for 15 weeks. Results showed that the n-3 deficiency increased parameters of anxiety-like behavior using open field and elevated plus maze tests in the male offspring. Behavioral changes were accompanied by a level reduction in the anxiolytic-related neuropeptide Y-1 receptor, and an increase in the anxiogenic-related glucocorticoid receptor in the cognitive related frontal cortex, hypothalamus and hippocampus. The n-3 deficiency reduced brain levels of docosahexaenoic acid (DHA) and increased the ratio n-6/n-3 assessed by gas chromatography. The n-3 deficiency reduced the levels of BDNF and signaling through the BDNF receptor TrkB, in proportion to brain DHA levels, and reduced the activation of the BDNF-related signaling molecule CREB in selected brain regions. The n-3 deficiency also disrupted the insulin signaling pathways as evidenced by changes in insulin receptor (IR) and insulin receptor substrate (IRS). DHA deficiency during brain maturation reduces plasticity and compromises brain function in adulthood. Adequate levels of dietary DHA seem crucial for building long-term neuronal resilience for optimal brain performance and aiding in the battle against neurological disorders.
authors.affiliation: Department of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Harsharan Singh
authors.initials: HS
authors.lastname: Bhatia
authors.forename: Rahul
authors.initials: R
authors.lastname: Agrawal
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sharma
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Huo
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ying
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomez-Pinilla
mesh_terms: D000821:Animal Feed; D000818:Animals; D001007:Anxiety / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001519:Behavior; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D018782:Maze Learning; D008954:Models, Biological; D009422:Nervous System Diseases / Q000517:prevention & control; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats
chemical_list: D015525:Fatty Acids, Omega-3; D051100:Glial Cell Line-Derived Neurotrophic Factor; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid