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Differential Gene Expression in Brain Post Repeated Blast Exposures

Study on gene expression changes in mouse brain after repeated blast exposures, revealing alterations in auditory-related genes and potential mechanisms of hearing impairment.

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Differential Gene Expression in Brain Post Repeated Blast Exposures

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  1. Preliminary studies on differential expression of auditory functional genes in the brain after repeated blast exposures Manojkumar Valiyaveettil, PhD; Yonas Alamneh, MS; Stacy-Ann Miller, BS; Rasha Hammamieh, PhD; Ying Wang, MD; Peethambaran Arun, PhD; Yanling Wei, MD; Samuel Oguntayo; Madhusoodana P. Nambiar, PhD

  2. Aim • Determine differential expression of auditory-related genes in various regions of brain by using complementary DNA microarray analysis. • Relevance • Mechanisms of central auditory processing in auditory/vestibular injuries and subsequent tinnitus and hearing loss in Active Duty servicemembers exposed to blast are unknown.

  3. Methods • Analyzed hearing-related gene expression in different brain regions after repeated blast exposures in mice. • Mice were exposed to repeated blast exposures (20.6 psi) using shock tube. • 6 hours after last blast exposure, 3 animals each from sham and blast groups were euthanized. • Brain tissue was collected and snap frozen. • Remaining 3 mice in each group were sacrificed 24 hours after last blast exposure and used for histopathology.

  4. Results • Otoferlin, otoancorin: • Expression significantly changed in hippocampus. • Cadherin, protocadherin: • Differential expression in hippocampus, cerebellum, frontal cortex, midbrain. • Calcium-signaling genes involved in auditory signal processing significantly altered. • Hearing loss-related antioxidant enzymes: • Hippocampus and midbrain showed significantly increased gene expression. • Histopathology: • Significant injury in inner layer of auditory cortex.

  5. Neuropathology of auditory cortex exposed to repeated blasts. Two close proximities of auditory cortex ((a) and (b) in leftmost panel) were analyzed for severity of injury in sham control ((a1) and (b1)) and repeated blast-exposed ((a2) and (b2)) mice 24 h after last blast exposure. Positive silver staining evident in auditory cortex of repeated blast-exposed mice confirming neurodegeneration (n = 3 for sham and blast).

  6. Conclusion • Mice exposed to repeated blasts showed injury to auditory cortex and significant alterations in multiple genes known to be involved in age- and noise-induced hearing impairment.

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