Gene-environment interaction promotes Alzheimer's risk as revealed by synergy of repeated mild traumatic brain injury and mouse App knock-in
Chiasseu M, Fesharaki-Zadeh A, Saito T, Saido TC, Strittmatter SM. Gene-environment interaction promotes Alzheimer's risk as revealed by synergy of repeated mild traumatic brain injury and mouse App knock-in. Neurobiology Of Disease 2020, 145: 105059. PMID: 32858147, PMCID: PMC7572902, DOI: 10.1016/j.nbd.2020.105059.Peer-Reviewed Original ResearchConceptsMild traumatic brain injuryTraumatic brain injuryAlzheimer's diseaseBrain injuryGene-environment interactionsMild closed head injuryMorris water maze testAge-matched wild-type controlsStrong unmet needAccumulation of amyloidAge-matched miceClosed head injuryWater maze testNovel object recognitionPersistent cognitive deficitsProtein gene mutationsIba1 expressionWild-type controlsPhospho-tauClinical manifestationsAD pathologyAD symptomsHead injuryAD pathogenesisRisk factorsFyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy
Tang SJ, Fesharaki-Zadeh A, Takahashi H, Nies SH, Smith LM, Luo A, Chyung A, Chiasseu M, Strittmatter SM. Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy. Acta Neuropathologica Communications 2020, 8: 96. PMID: 32611392, PMCID: PMC7329553, DOI: 10.1186/s40478-020-00976-9.Peer-Reviewed Original ResearchConceptsRepetitive closed head injuriesMemory deficitsPhospho-tau accumulationChronic variable stressPersistent memory deficitsP301S transgenic miceClosed head injuryFyn inhibitionPassive avoidance learningFyn kinaseGlial activationPhospho-tauPresynaptic markersSynapse lossTau accumulationHead injurySynapse densityPhosphorylated tauTherapeutic benefitTransgenic miceBehavioral improvementTrauma modelTauopathiesSpatial memoryAvoidance learningIncreased Behavioral Deficits and Inflammation in a Mouse Model of Co-Morbid Traumatic Brain Injury and Post-Traumatic Stress Disorder
Fesharaki-Zadeh A, Miyauchi JT, St. Laurent-Arriot K, Tsirka SE, Bergold PJ. Increased Behavioral Deficits and Inflammation in a Mouse Model of Co-Morbid Traumatic Brain Injury and Post-Traumatic Stress Disorder. ASN Neuro 2020, 12: 1759091420979567. PMID: 33342261, PMCID: PMC7755938, DOI: 10.1177/1759091420979567.Peer-Reviewed Original ResearchConceptsTraumatic brain injuryPost-traumatic stress disorderChi groupBrain injuryBarnes mazeCo-morbid traumatic brain injuryMale C57/BL6 miceCognitive deficitsComorbid post-traumatic stress disorderC57/BL6 miceStress disorderClosed-head modelIba-1 levelsChronic variable stress modelActive place avoidancePlace avoidanceGreater cognitive deficitsNeuroinflammatory outcomesBasal anxiety levelsCVS groupSham treatmentBL6 miceBehavioral deficitsMouse modelKey underlying mechanism