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Repeat Mild Traumatic Brain Injury in Adolescent Rats Increases Subsequent ?-Amyloid Pathogenesis.

ABSTRACT: Single moderate-to-severe traumatic brain injuries (TBIs) may increase subsequent risk for neurodegenerative disease by facilitating ?-amyloid (A?) deposition. However, the chronic effects on A? pathogenesis of repetitive mild TBIs (rTBI), which are common in adolescents and young adults, remain uncertain. We examined the effects of rTBI sustained during adolescence on subsequent deposition of A? pathology in a transgenic APP/PS1 rat model. Transgenic rats received sham or four individual mild TBIs (rTBIs) separated by either 24- or 72-h intervals at post-natal day 35 (before A? plaque deposition). Animals were euthanized at 12 months of age and underwent immunohistochemical analyses of A? plaque deposition. Significantly greater hippocampal A? plaque deposition was observed after rTBI separated by 24?h relative to rTBI separated by 72?h or sham injuries. These increases in hippocampal A? plaque load were driven by increases in both plaque number and size. Similar, though less-pronounced, effects were observed in extrahippocampal regions. Increases in A? plaque deposition were observed both ipsilaterally and contralaterally to the injury site and in both males and females. rTBIs sustained in adolescence can increase subsequent deposition of A? pathology, and these effects are critically dependent on interinjury interval.

SUBMITTER: Grant DA

PROVIDER: S-EPMC6909680 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Repeat Mild Traumatic Brain Injury in Adolescent Rats Increases Subsequent β-Amyloid Pathogenesis.

Grant Daya A DA Serpa Rebecka R Moattari Cameron R CR Brown Ari A Greco Tiffany T Prins Mayumi L ML Teng Edmond E

Journal of neurotrauma 20171027 1

Single moderate-to-severe traumatic brain injuries (TBIs) may increase subsequent risk for neurodegenerative disease by facilitating β-amyloid (Aβ) deposition. However, the chronic effects on Aβ pathogenesis of repetitive mild TBIs (rTBI), which are common in adolescents and young adults, remain uncertain. We examined the effects of rTBI sustained during adolescence on subsequent deposition of Aβ pathology in a transgenic APP/PS1 rat model. Transgenic rats received sham or four individual mild T ...[more]

PMID: 28728464

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Project description:Mild traumatic brain injury (mTBI) or concussion is a common injury worldwide leading to substantial medical costs and a high burden on society. In adolescents, falls and sports related trauma are often the causes of mTBI. Importantly, critical brain growth and development occurs during this sensitive period making the prospect of a brain injury a worrying phenomenon. Upwards of 70% of patients report circadian disruption following these injuries and this has been shown to impede recovery. Therefore, we sought to determine if core circadian clock gene expression was disrupted in rat model of repetitive mTBI (RmTBI). Male and female adolescent rats (n = 129) received sham or RmTBI. The animals were then euthanized at different times throughout the day and night. Tissue from the hypothalamus, cerebellum, hippocampus, liver, and small intestine were evaluated for the expression of per1, per2, cry1, clock, bmal1 and rev-erb-α. We found most clock genes varied across the day/night indicating circadian expression patterns. In the hypothalamus we found RmTBI altered the expression of cry1 and bmal1 in addition to sex differences in per2, cry1, clock, bmal1 and rev-erb- α. In the cerebellum, per1, per2, cry1, clock, bmal1 and rev-erb-α rhythms were all knocked out by RmTBI in addition to sex differences in cry1, clock and bmal1 expression. We also detected a significant decrease in overall expression of all clock genes in males in the middle of the night. In the hippocampus we found that RmTBI changed the rhythm of rev-erb-α expression in addition to sex differences in bmal1 expression. In the liver we detected strong rhythms in all genes examined, however only per2 expression was knocked out by RmTBI, in addition we also detected sex differences in per2 and cry1. We also detected an overall decrease in female clock gene expression in the early night. In the small intestine, RmTBI altered cry1 expression and there were sex differences in rev-erb-α. These results indicate that RmTBI alters core circadian clock gene expression in the central and peripheral nervous system in a time, tissue and sex dependent manner. This may be disrupting important phase relationships between the brain and peripheral nervous system and contributing to post-injury symptomology and also highlights the importance for time and sex dependent assessment of injury outcomes.

Dataset Information

Repeat Mild Traumatic Brain Injury in Adolescent Rats Increases Subsequent ?-Amyloid Pathogenesis.

Publications

Repeat Mild Traumatic Brain Injury in Adolescent Rats Increases Subsequent β-Amyloid Pathogenesis.

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