title: TBI and sex: crucial role of progesterone protecting the brain in an omega-3 deficient condition.
abstract: We assessed whether the protective action of progesterone on traumatic brain injury (TBI) could be influenced by the consumption of omega-3 fatty acids during early life. Pregnant Sprague-Dawley rats were fed on omega-3 adequate or deficient diet from 3rd day of pregnancy and their female offspring were kept on the same diets up to the age of 15 weeks. Ovariectomy was performed at the age of 12 weeks to deprive animals from endogenous steroids until the time of a fluid percussion injury (FPI). Dietary n-3 fatty acid deficiency increased anxiety in sham animals and TBI aggravated the effects of the deficiency. Progesterone replacement counteracted the effects of TBI on the animals reared under n-3 deficiency. A similar pattern was observed for markers of membrane homeostasis such as 4-Hydroxynonenal (HNE) and secreted phospholipases A2 (sPLA2), synaptic plasticity such as brain derived neurotrophic factor (BDNF), syntaxin (STX)-3 and growth associated protein (GAP)-43, and for growth inhibitory molecules such as myelin-associated glycoprotein (MAG) and Nogo-A. Results that progesterone had no effects on sham n-3 deficient animals suggest that the availability of progesterone is essential under injury conditions. Progesterone treatment counteracted several parameters related to synaptic plasticity and membrane stability reduced by FPI and n-3 deficiency suggest potential targets for therapeutic applications. These results reveal the importance of n-3 preconditioning during early life and the efficacy of progesterone therapy during adulthood to counteract weaknesses in neuronal and behavioral plasticity.
authors.affiliation: Department of Integrative Biology & Physiology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Ethika
authors.initials: E
authors.lastname: Tyagi
authors.affiliation: Department of Integrative Biology & Physiology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Rahul
authors.initials: R
authors.lastname: Agrawal
authors.affiliation: Department of Integrative Biology & Physiology, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Ying
authors.affiliation: Department of Integrative Biology & Physiology, UCLA, Los Angeles, CA 90095, USA; Department of Neurosurgery, UCLA Brain Injury Research Center, Los Angeles, CA 90095, USA. Electronic address: fgomezpi@ucla.edu.
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomez-Pinilla
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology; D001930:Brain Injuries / Q000150:complications / Q000209:etiology / Q000517:prevention & control*; D004041:Dietary Fats / Q000494:pharmacology*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009185:Myelin Proteins / Q000633:toxicity; D018992:Myelin-Associated Glycoprotein / Q000633:toxicity; D009478:Neuropeptide Y / Q000378:metabolism; D000070798:Nogo Proteins; D010052:Ovariectomy; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011374:Progesterone / Q000627:therapeutic use*; D011372:Progestins / Q000627:therapeutic use*; D050765:Qa-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D019922:GAP-43 Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D009478:Neuropeptide Y; D000070798:Nogo Proteins; D011372:Progestins; D050765:Qa-SNARE Proteins; C000603197:Rtn4 protein, rat; D011374:Progesterone
keywords: Anxiety; Neuroplasticity; Omega−3 fatty acid; Progesterone; Traumatic brain injury