title: Conjugated Linoleic Acid Administration Induces Amnesia in Male Sprague Dawley Rats and Exacerbates Recovery from Functional Deficits Induced by a Controlled Cortical Impact Injury.
abstract: Long-chain polyunsaturated fatty acids like conjugated linoleic acids (CLA) are required for normal neural development and cognitive function and have been ascribed various beneficial functions. Recently, oral CLA also has been shown to increase testosterone (T) biosynthesis, which is known to diminish traumatic brain injury (TBI)-induced neuropathology and reduce deficits induced by stroke in adult rats. To test the impact of CLA on cognitive recovery following a TBI, 5-6 month old male Sprague Dawley rats received a focal injury (craniectomy + controlled cortical impact (CCI; n = 17)) or Sham injury (craniectomy alone; n = 12) and were injected with 25 mg/kg body weight of Clarinol® G-80 (80% CLA in safflower oil; n = 16) or saline (n = 13) every 48 h for 4 weeks. Sham surgery decreased baseline plasma progesterone (P4) by 64.2% (from 9.5 ± 3.4 ng/mL to 3.4 ± 0.5 ng/mL; p = 0.068), T by 74.6% (from 5.9 ± 1.2 ng/mL to 1.5 ± 0.3 ng/mL; p < 0.05), 11-deoxycorticosterone (11-DOC) by 37.5% (from 289.3 ± 42.0 ng/mL to 180.7 ± 3.3 ng/mL), and corticosterone by 50.8% (from 195.1 ± 22.4 ng/mL to 95.9 ± 2.2 ng/mL), by post-surgery day 1. CCI injury induced similar declines in P4, T, 11-DOC and corticosterone (58.9%, 74.6%, 39.4% and 24.6%, respectively) by post-surgery day 1. These results suggest that both Sham surgery and CCI injury induce hypogonadism and hypoadrenalism in adult male rats. CLA treatment did not reverse hypogonadism in Sham (P4: 2.5 ± 1.0 ng/mL; T: 0.9 ± 0.2 ng/mL) or CCI-injured (P4: 2.2 ± 0.9 ng/mL; T: 1.0 ± 0.2 ng/mL, p > 0.05) animals by post-injury day 29, but rapidly reversed by post-injury day 1 the hypoadrenalism in Sham (11-DOC: 372.6 ± 36.6 ng/mL; corticosterone: 202.6 ± 15.6 ng/mL) and CCI-injured (11-DOC: 384.2 ± 101.3 ng/mL; corticosterone: 234.6 ± 43.8 ng/mL) animals. In Sham surgery animals, CLA did not alter body weight, but did markedly increase latency to find the hidden Morris Water Maze platform (40.3 ± 13.0 s) compared to saline treated Sham animals (8.8 ± 1.7 s). In CCI injured animals, CLA did not alter CCI-induced body weight loss, CCI-induced cystic infarct size, or deficits in rotarod performance. However, like Sham animals, CLA injections exacerbated the latency of CCI-injured rats to find the hidden MWM platform (66.8 ± 10.6 s) compared to CCI-injured rats treated with saline (30.7 ± 5.5 s, p < 0.05). These results indicate that chronic treatment of CLA at a dose of 25 mg/kg body weight in adult male rats over 1-month 1) does not reverse craniectomy- and craniectomy + CCI-induced hypogonadism, but does reverse craniectomy- and craniectomy + CCI-induced hypoadrenalism, 2) is detrimental to medium- and long-term spatial learning and memory in craniectomized uninjured rats, 3) limits cognitive recovery following a moderate-severe CCI injury, and 4) does not alter body weight.
authors.affiliation: Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.
authors.forename: Rastafa I
authors.initials: RI
authors.lastname: Geddes
authors.affiliation: Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.
authors.forename: Quinn
authors.initials: Q
authors.lastname: Bongers
authors.affiliation: Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.
authors.forename: Marlyse
authors.initials: M
authors.lastname: Wehber
authors.affiliation: Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.
authors.forename: Icelle M
authors.initials: IM
authors.lastname: Anderson
authors.affiliation: Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.
authors.forename: Alex D
authors.initials: AD
authors.lastname: Jansen
authors.affiliation: Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.
authors.forename: Chase
authors.initials: C
authors.lastname: Nier
authors.affiliation: Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.
authors.forename: Emily
authors.initials: E
authors.lastname: Fares
authors.affiliation: Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Farquhar
authors.affiliation: Assay Services Unit and Institute for Clinical and Translational Research Core Laboratory, National Primate Research Center, University of Wisconsin-Madison, Wisconsin, United States of America.
authors.forename: Amita
authors.initials: A
authors.lastname: Kapoor
authors.affiliation: Assay Services Unit and Institute for Clinical and Translational Research Core Laboratory, National Primate Research Center, University of Wisconsin-Madison, Wisconsin, United States of America.
authors.forename: Toni E
authors.initials: TE
authors.lastname: Ziegler
authors.affiliation: Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.
authors.forename: Sivan
authors.initials: S
authors.lastname: VadakkadathMeethal
authors.affiliation: Department of Obstetrics and Gynecology, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Bird
authors.affiliation: Division of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Wisconsin, United States of America.|Geriatric Research, Education and Clinical Center, Veterans Administration Hospital, Madison, Wisconsin, United States of America.|School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
authors.forename: Craig S
authors.identifier: http://orcid.org/0000-0001-5040-1679
authors.initials: CS
authors.lastname: Atwood
mesh_terms: D000647:Amnesia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D000818:Animals; D001930:Brain Injuries / Q000097:blood / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000097:blood / Q000503:physiopathology*; D003345:Corticosterone / Q000097:blood; D003900:Desoxycorticosterone / Q000097:blood; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*
chemical_list: D044243:Linoleic Acids, Conjugated; D003900:Desoxycorticosterone; D011374:Progesterone; D003345:Corticosterone