title: Moderate traumatic brain injury is linked to acute behaviour deficits and long term mitochondrial alterations.
abstract: Traumatic brain injury (TBI) remains one of the leading causes of death and disability worldwide. Mild TBI may lead to neuropsychiatric sequelae, including memory loss and motor impairment. Mitochondrial dysfunction and oxidative stress have a contributory role in several neurological disorders; however, their association with mitophagy in mild TBI is unclear. TBI was induced in female Sprague Dawley (SD) rats using a New York University Impactor (10 g, impactor head 2.5 mm diameter, weight drop 50 mm) and compared to sham surgery controls. The novel object recognition and error ladder tests were performed at 24 hours and for 6 weeks post injury, and the brains were examined histologically to confirm the extent of injury. Mitochondria manganese superoxide dismutase (MnSOD) and the oxidative phosphorylation (OXPHOS) complexes I-V (CI-CV), as well as mitophagy markers, dynamin related protein 1 (DRP-1), LC3A/B and PTEN-induced putative kinase 1 (PINK-1), were measured in the penumbra by western blot. At 24 hours sham rats performed as expected on a novel object recognition test while TBI rats showed cognitive deficits at the early time points. TBI rats also showed more early motor deficits on a horizontal ladder, compared with the sham rats. MnSOD, OXPHOS CI, CIII and CV protein levels were significantly lower in the TBI group at 24 hours. DRP-1, LC3A/B I and II, and PINK-1 were increased at 6 weeks suggesting abnormal mitophagy. Moderate TBI caused immediate cognitive and mild motor functional deficits in the rats that did not persist. Reduced antioxidative capacity and possibly compromised mitochondrial function may affect the long term functional recovery.
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia. hui.chen-1@uts.edu.au.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia.
authors.forename: Yik Lung
authors.initials: YL
authors.lastname: Chan
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia.|Kolling Institute of Medical Research, University of Sydney, St Leonards, NSW, Australia.
authors.forename: Long The
authors.initials: LT
authors.lastname: Nguyen
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Mao
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia.
authors.forename: Alicia
authors.initials: A
authors.lastname: de Rosa
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia.|School of Chemical Life Sciences, Singapore Polytechnic, Singapore.
authors.forename: Ing Tsyr
authors.initials: IT
authors.lastname: Beh
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia.|School of Chemical Life Sciences, Singapore Polytechnic, Singapore.
authors.forename: Candice
authors.initials: C
authors.lastname: Chee
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia.
authors.forename: Brian
authors.initials: B
authors.lastname: Oliver
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia.
authors.forename: George
authors.initials: G
authors.lastname: Herok
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia.|Kolling Institute of Medical Research, University of Sydney, St Leonards, NSW, Australia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Saad
authors.affiliation: School of Life Sciences, Faculty of Science, University of Technology Sydney, Broadway, NSW, Australia. catherine.gorrie@uts.edu.au.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gorrie
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001924:Brain Concussion / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: behavioural studies; immunohistochemistry; mitochondria; mitophagy; oxidative stress; rat brain; trauma