title: Sociosexual and communication deficits after traumatic injury to the developing murine brain.
abstract: Despite the life-long implications of social and communication dysfunction after pediatric traumatic brain injury, there is a poor understanding of these deficits in terms of their developmental trajectory and underlying mechanisms. In a well-characterized murine model of pediatric brain injury, we recently demonstrated that pronounced deficits in social interactions emerge across maturation to adulthood after injury at postnatal day (p) 21, approximating a toddler-aged child. Extending these findings, we here hypothesized that these social deficits are dependent upon brain maturation at the time of injury, and coincide with abnormal sociosexual behaviors and communication. Age-dependent vulnerability of the developing brain to social deficits was addressed by comparing behavioral and neuroanatomical outcomes in mice injured at either a pediatric age (p21) or during adolescence (p35). Sociosexual behaviors including social investigation and mounting were evaluated in a resident-intruder paradigm at adulthood. These outcomes were complemented by assays of urine scent marking and ultrasonic vocalizations as indices of social communication. We provide evidence of sociosexual deficits after brain injury at p21, which manifest as reduced mounting behavior and scent marking towards an unfamiliar female at adulthood. In contrast, with the exception of the loss of social recognition in a three-chamber social approach task, mice that received TBI at adolescence were remarkably resilient to social deficits at adulthood. Increased emission of ultrasonic vocalizations (USVs) as well as preferential emission of high frequency USVs after injury was dependent upon both the stimulus and prior social experience. Contrary to the hypothesis that changes in white matter volume may underlie social dysfunction, injury at both p21 and p35 resulted in a similar degree of atrophy of the corpus callosum by adulthood. However, loss of hippocampal tissue was greater after p21 compared to p35 injury, suggesting that a longer period of lesion progression or differences in the kinetics of secondary pathogenesis after p21 injury may contribute to observed behavioral differences. Together, these findings indicate vulnerability of the developing brain to social dysfunction, and suggest that a younger age-at-insult results in poorer social and sociosexual outcomes.
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States of America; Department of Medicine (Royal Melbourne Hospital), Melbourne Brain Centre, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Bridgette D
authors.initials: BD
authors.lastname: Semple
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States of America; Department of Physical Therapy and Rehabilitation, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Noble-Haeusslein
authors.affiliation: Department of Physics, Randolph College, Lynchburg, Virginia, United States of America.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jun Kwon
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States of America; San Francisco State University, San Francisco, California, United States of America.
authors.forename: Pingdewinde N
authors.initials: PN
authors.lastname: Sam
authors.affiliation: Department of Physics, Randolph College, Lynchburg, Virginia, United States of America.
authors.forename: A Matt
authors.initials: AM
authors.lastname: Gibson
authors.affiliation: Department of Physics, Randolph College, Lynchburg, Virginia, United States of America.
authors.forename: Sarah
authors.initials: S
authors.lastname: Grissom
authors.affiliation: Department of Physics, Randolph College, Lynchburg, Virginia, United States of America.
authors.forename: Sienna
authors.initials: S
authors.lastname: Brown
authors.affiliation: Department of Physics, Randolph College, Lynchburg, Virginia, United States of America.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Adahman
authors.affiliation: Department of Physics, Randolph College, Lynchburg, Virginia, United States of America.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Hollingsworth
authors.affiliation: Department of Physics, Randolph College, Lynchburg, Virginia, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kwakye
authors.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Kayleen
authors.initials: K
authors.lastname: Gimlin
authors.affiliation: Physical Medicine and Rehabilitation Alliance of Baylor College of Medicine and the University of Texas-Houston Medical School, Houston, Texas, United States of America; Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, United States of America.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Wilde
authors.affiliation: Physical Medicine and Rehabilitation Alliance of Baylor College of Medicine and the University of Texas-Houston Medical School, Houston, Texas, United States of America.
authors.forename: Gerri
authors.initials: G
authors.lastname: Hanten
authors.affiliation: Physical Medicine and Rehabilitation Alliance of Baylor College of Medicine and the University of Texas-Houston Medical School, Houston, Texas, United States of America; Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, United States of America.
authors.forename: Harvey S
authors.initials: HS
authors.lastname: Levin
authors.affiliation: Department of Physics, Randolph College, Lynchburg, Virginia, United States of America.
authors.forename: A Katrin
authors.initials: AK
authors.lastname: Schenk
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000254:growth & development*; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology; D003147:Communication Disorders / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012725:Sexual Behavior / Q000502:physiology*; D012919:Social Behavior; D014828:Vocalization, Animal / Q000502:physiology
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