title: Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice.
abstract: Extensive tau-immunoreactive neurons and glial cells associated with chronic traumatic encephalopathy (CTE) have been documented in the brains of some professional athletes and others with a history of repetitive mild traumatic brain injury (r-mTBI). The neuropathology and tau involvement in mTBI have not been extensively studied in animal models, particularly in aged animals. We investigated the effects of single mTBI (s-mTBI) and r-mTBI in 18-month-old hTau mice, which express wild-type human tau isoforms on a null murine tau background (n = 3-5 per group). At this age, hTau mice already demonstrate tau pathology, but there was a significant increase in phospho-tau immunoreactivity in response to r-mTBI, but not to s-mTBI,as determined using multiple phospho-tau-specific antibodies. Repetitive mTBI also resulted in a marked increase in astrocyte/microglia activation notably in the superficial layer of the motor/somatosensory cortex and the corpus callosum. We did not observe the perivascular tau pathology, neuritic threads, or astrocytic tangles that are commonly found in human CTE. The increase in phospho-tau in the r-mTBI mice suggests that this may be a useful model for investigating further the link between mTBI, particularly r-mTBI, and tau pathobiology in CTE and in understanding responses of the aged brain to mTBI.
authors: Roskamp Institute, Sarasota, Florida 34243, USA. bojo@roskampinstitute.net
authors: Joseph-Olubunmi
authors: JO
authors: Ojo
authors: Benoit
authors: B
authors: Mouzon
authors: M Banks
authors: MB
authors: Greenberg
authors: Corbin
authors: C
authors: Bachmeier
authors: Mike
authors: M
authors: Mullan
authors: Fiona
authors: F
authors: Crawford
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D001930:Brain Injuries / Q000150:complications*; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D000939:Epitopes / Q000378:metabolism; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D063146:Polycomb-Group Proteins; D024801:Tauopathies / Q000150:complications / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D000939:Epitopes; C455179:F3 epitope; D005904:Glial Fibrillary Acidic Protein; C054369:MAPT protein, human; D009419:Nerve Tissue Proteins; C533390:Phf1 protein, mouse; D063146:Polycomb-Group Proteins; D014157:Transcription Factors; D016875:tau Proteins; D017493:Leukocyte Common Antigens