Publications by authors named "M Patricia Mullan"
The impact of APOE4 on neurological symptoms after exposure to K. brevis neurotoxin.
Environ Toxicol Pharmacol
January 2025
Introduction: The harmful alga Karenia brevis (K. brevis) releases brevetoxins (PbTx) that cause respiratory and neurological symptoms. The apolipoprotein E (APOE) ε4 allele has been linked to poor neurological outcomes after exposure to environmental toxicants.
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- A study found that changes in the brain entorhinal cortex (EC) and specific blood lipids are linked to Alzheimer's disease (AD) in individuals with the apolipoprotein E ε4 genetic variant.
- Analysis of brain imaging and lipid profiles revealed that ε4 carriers with mild traumatic brain injury (mTBI) had thicker left ECs, but repeated mTBIs reduced right EC thickness.
- The research highlights the need for further investigation into the relationship between ε4, mTBI, and specific blood lipid ratios as potential biomarkers for early detection of AD in affected individuals.
Chronic neuroinflammation and microglial activation are key mediators of the secondary injury cascades and cognitive impairment that follow exposure to repetitive mild traumatic brain injury (r-mTBI). Peroxisome proliferator-activated receptor-γ (PPARγ) is expressed on microglia and brain resident myeloid cell types and their signaling plays a major anti-inflammatory role in modulating microglial responses. At chronic timepoints following injury, constitutive PPARγ signaling is thought to be dysregulated, thus releasing the inhibitory brakes on chronically activated microglia.
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- Epidemiological studies show a strong link between repetitive mild traumatic brain injury (r-mTBI) and increased risk of developing neurodegenerative disorders like chronic traumatic encephalopathy (CTE), with one major feature being the buildup of hyperphosphorylated tau in neurons.
- Research using a mouse model suggests that while r-mTBI doesn't worsen tau astrogliopathy, it does lead to increased phosphorylated tau at the injury site and significant changes in biological functions of tau-bearing astrocytes.
- The findings imply that understanding tau astrogliopathy is crucial for determining how it contributes to brain injury and could help identify potential treatments for r-mTBI and CTE.
Repetitive mild traumatic brain injuries (r-mTBI) sustained in the military or contact sports have been associated with the accumulation of extracellular tau in the brain, which may contribute to the pathogenesis of neurodegenerative tauopathies. The expression of the apolipoprotein E4 (apoE4) isoform has been associated with higher levels of tau in the brain, and worse clinical outcomes after r-mTBI, though the influence of apoE genotype on extracellular tau dynamics in the brain is poorly understood. We recently demonstrated that extracellular tau can be eliminated across blood-brain barrier (BBB), which is progressively impaired following r-mTBI.
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