TY - JOUR
T1 - Investigating the Role of the Hypothalamus in Outcomes to Repetitive Mild Traumatic Brain Injury
T2 - Neonatal Monosodium Glutamate Does Not Exacerbate Deficits
AU - Yamakawa, Glenn
AU - Weerawardhena, Himanthri
AU - Eyolfson, Eric
AU - Griep, Yannick
AU - Antle, Michael C.
AU - Mychasiuk, Richelle
PY - 2019/8/10
Y1 - 2019/8/10
N2 - Repetitive mild traumatic brain injury (RmTBI) is a prevalent and costly head injury particularly among adolescents. These injuries may result in long-term consequences, especially during this critical period of development. Insomnia and sleeping difficulties are frequently reported following RmTBI and greatly impair recovery. We sought to develop an animal model of exacerbated deficits following RmTBI by disrupting the hypothalamic circadian system. To accomplish this, we conducted RmTBI on adolescent rats that had received neonatal injections of monosodium glutamate (MSG), a known hypothalamic neurotoxin. We then examined behavioral, circadian, and epigenetic changes. MSG treated rats showed lower anxiety-like behaviors and displayed poor short-term working memory. We also showed changes in the morphology of the circadian clock in the suprachiasmatic nucleus (SCN) vasoactive intestinal polypeptide (VIP) immunostaining. VIP optical density in the SCN increased with MSG but decreased with RmTBI. There were changes in the expression of the clock genes and upregulation of the orexin receptors in response to RmTBI. MSG treated rats had longer telomere lengths than controls. Finally, although both MSG and RmTBI alone produced attenuated circadian amplitudes of activity and body temperature, exacerbated deficits were not identified in animals that received MSG and RmTBI. In sum, both MSG and RmTBI can alter behavior, circadian rhythm amplitude, SCN morphology, and gene expression independently, but the effects do not appear to be additive. Specific damage in the hypothalamus and SCN should be considered when patients experience sleeping problems following RmTBI, as this may improve therapeutic strategies.
AB - Repetitive mild traumatic brain injury (RmTBI) is a prevalent and costly head injury particularly among adolescents. These injuries may result in long-term consequences, especially during this critical period of development. Insomnia and sleeping difficulties are frequently reported following RmTBI and greatly impair recovery. We sought to develop an animal model of exacerbated deficits following RmTBI by disrupting the hypothalamic circadian system. To accomplish this, we conducted RmTBI on adolescent rats that had received neonatal injections of monosodium glutamate (MSG), a known hypothalamic neurotoxin. We then examined behavioral, circadian, and epigenetic changes. MSG treated rats showed lower anxiety-like behaviors and displayed poor short-term working memory. We also showed changes in the morphology of the circadian clock in the suprachiasmatic nucleus (SCN) vasoactive intestinal polypeptide (VIP) immunostaining. VIP optical density in the SCN increased with MSG but decreased with RmTBI. There were changes in the expression of the clock genes and upregulation of the orexin receptors in response to RmTBI. MSG treated rats had longer telomere lengths than controls. Finally, although both MSG and RmTBI alone produced attenuated circadian amplitudes of activity and body temperature, exacerbated deficits were not identified in animals that received MSG and RmTBI. In sum, both MSG and RmTBI can alter behavior, circadian rhythm amplitude, SCN morphology, and gene expression independently, but the effects do not appear to be additive. Specific damage in the hypothalamus and SCN should be considered when patients experience sleeping problems following RmTBI, as this may improve therapeutic strategies.
KW - Behavior
KW - Circadian
KW - Concussion
KW - Gene expression
KW - Suprachiasmatic nucleus
KW - Telomere
UR - http://www.scopus.com/inward/record.url?scp=85068801532&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2019.06.022
DO - 10.1016/j.neuroscience.2019.06.022
M3 - Article
C2 - 31254543
AN - SCOPUS:85068801532
SN - 0306-4522
VL - 413
SP - 264
EP - 278
JO - Neuroscience
JF - Neuroscience
ER -