Altered amyloid precursor protein, tau‐regulatory proteins, neuronal numbers and behaviour, but no tau pathology, synaptic and inflammatory changes or memory deficits, at 1 month following repetitive mild traumatic brain injury. (11th July 2022)

• Record Type: Journal Article
• Authors: Juan, Sydney M. A.; Daglas, Maria; Adlard, Paul A.
• Other Names: Porsteinsson Anton P. guestEditor.; Rangaraju Srikant guestEditor.; Spires‐Jones Tara L. guestEditor.; O'Banion Kerry guestEditor.
• Is Part Of: European journal of neuroscience. Volume 56:Number 9(2022)
• Page Start: 5342
• Page End: 5367
• Publication Date: 2022-07-11
• Subjects: kinases -- neurodegeneration -- phosphatases -- repeat head trauma -- tau pathology; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.15752
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Repetitive mild traumatic brain injury, commonly experienced following sports injuries, results in various secondary injury processes and is increasingly recognised as a risk factor for the development of neurodegenerative conditions such as chronic traumatic encephalopathy, which is characterised by tau pathology. We aimed to characterise the underlying pathological mechanisms that might contribute to the onset of neurodegeneration and behavioural changes in the less‐explored subacute (1‐month) period following single or repetitive controlled cortical impact injury (five impacts, 48 h apart) in 12‐week‐old male and female C57Bl6 mice. We conducted motor and cognitive testing, extensively characterised the status of tau and its regulatory proteins via western blot and quantified neuronal populations using stereology. We report that r‐mTBI resulted in neurobehavioural deficits, gait impairments and anxiety‐like behaviour at 1 month post‐injury, effects not seen following a single injury. R‐mTBI caused a significant increase in amyloid precursor protein, an increased trend towards tau phosphorylation and significant changes in kinase/phosphatase proteins that may promote a downstream increase in tau phosphorylation, but no changes in synaptic or neuroinflammatory markers. Lastly, we report neuronal loss in various brain regions following both single and repeat injuries. We demonstrate herein that repeated impacts are required to promote the initiation of a cascade of biochemical events that are consistent with the onset of neurodegeneration subacutely post‐injury. Identifying the timeframe in which these changes occur and the pathological mechanisms involved will be crucial for the development of future therapeutics to prevent the onset or mitigate the progression of neurodegeneration following r‐mTBI. Abstract : We studied whether repetitive mild traumatic brain injury (r‐mTBI) would lead to pathological changes consistent with the initiation of neurodegeneration at 1 month post‐injury. R‐mTBI led to increased APP levels, altered kinase and phosphatase proteins, neuron loss and behavioural deficits, but no changes in tau phosphorylation, synaptic and neuroinflammatory markers or memory function. This work demonstrates that r‐mTBI kick‐starts neurodegenerative processes as early as 1 month post‐injury.