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Neural architecture of Area 25 of the anterior cingulate cortex and its potential disruption in stage II chronic traumatic encephalopathy

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disorder that is associated with repetitive head injury (RHI), which includes both traumatic and subclinical brain injuries. Early CTE is a tauopathy that has patchy distribution of hyperphosphorylated tau within the depths of sulci which progressively spreads. Recent studies of RHI show that deep areas of the brain are most affected during head impacts, with strain due to shearing forces peaking at deep brain regions on the midline. The anterior cingulate cortex (ACC), which is directly on the midline, is likely one of the first regions to be affected by shearing forces yet there have been few studies of the cellular irregularities in the ACC at early stages of CTE. The present study investigated the proportions of inhibitory to excitatory neurons in a midline ACC area, Area 25 (A25), in neurotypical and stage II CTE cases using immunohistochemistry and Nissl staining to investigate neuronal subpopulation densities. Inhibitory neuron subpopulations in the human cortex can be labeled by three calcium binding proteins: parvalbumin (PV), calbindin (CB), and calretinin (CR). CB and PV interneurons differentially inhibit excitatory neurons while CR neurons in the upper cortical layers inhibit other inhibitory neurons, resulting in a disinhibitory effect. The results showed that the density of CB neurons significantly decreased in stage II CTE. In addition, CR neuron density may also be reduced but results for PV neurons were inconclusive. The disruption of inhibitory neurons in A25 may be an early change and may contribute to the early clinical presentation of CTE. A25 of the ACC is known to be involved in affective disorders and specifically is overactive in major depressive disorder, which is also experienced by individuals in the early stages of CTE. / 2026-09-26T00:00:00Z

Identiferoai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/49340
Date26 September 2024
CreatorsKozlov, Nika Phoebe
ContributorsBarbas, Helen, Zikopoulos, Vasileios
Source SetsBoston University
Languageen_US
Detected LanguageEnglish
TypeThesis/Dissertation

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