Efeito do exercício físico de natação sobre as alterações comportamentais e moleculares induzidas por concussões recorrentes no cérebro de ratos adolescentes

• Ano de defesa: 2025
• Autor(a) principal: Godinho, Douglas Buchmann
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; UFSM; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica; Centro de Ciências Naturais e Exatas
• Palavras-chave em Português: Concussão; Adolescência; Memória; Dopamina; Traumatismo cranioencefálico; Concussion; Adolescence; Memory; Dopamine; Traumatic brain injury; CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/37090

Recurrent concussions in adolescent athletes represent a serious public health concern, as they increase the risk of cognitive deficits, mental health disorders, and may lead to long-term neurodegenerative conditions. However, the consequences of exposure to repeated brain impacts occurring concomitantly with physical exercise remain poorly understood, particularly within the sports context. Therefore, the main objective of this thesis was to investigate the role of a chronic aerobic exercise protocol in the pathophysiology induced by recurrent concussions in young rats. The study aimed to characterize the effects of concussion in sedentary animals, assess the effects of exercise alone, and, crucially, examine how concurrent exercise might interact with concussive injuries, identifying the underlying molecular mechanisms of this interaction. Adolescent male Wistar rats were subjected to a protocol of ten concussions spaced over five weeks, with or without a concurrent progressive swimming regimen. Following the intervention period, the animals underwent a behavioral test battery to evaluate memory and locomotor activity, followed by collection of cerebral cortex and hippocampal samples for molecular analyses (Western blot and qRT-PCR). Results from the first study (Article 1) showed that recurrent concussions in sedentary animals induced a hyperactive phenotype and significant deficits in object location memory. These behavioral alterations were associated with disruptions in the cortical dopaminergic system, including reduced dopamine D2 receptor expression and decreased monoamine oxidase A (MAO-A) activity. The second study (Article 2), which examined exercise in isolation, revealed that the swimming protocol increased exploratory activity and upregulated markers of brain resilience, such as brain-derived neurotrophic factor (BDNF) and nuclear factor erythroid 2-related factor 2 (NRF2), without affecting memory performance under baseline conditions. The third study (Article 3) integrated these models and demonstrated a robust neuroprotective effect of exercise. Concurrent swimming completely prevented the spatial and short-term recognition memory deficits induced by concussions. Moreover, exercise modulated the hippocampal neuroinflammatory response, preventing GFAP upregulation and the expression of pro-inflammatory genes. Mechanistic investigation revealed that the protection conferred by exercise was associated with the preservation of dopamine D1 receptor (D1R) signaling in the hippocampus. While concussion in sedentary animals caused a marked reduction in D1R levels and in the phosphorylation of one of its downstream targets (PKA), exercise maintained the integrity of this signaling cascade. Collectively, these findings demonstrate that chronic physical exercise performed concurrently with repetitive concussions confers remarkable cognitive resilience. This protection does not arise from changes in classical neuroplasticity markers but rather from the selective preservation of hippocampal D1R signaling—a mechanism essential for memory consolidation and neuroinflammatory regulation. Thus, the D1R pathway emerges as a central target both for concussion-induced deficits and for exercise-mediated neuroprotection, representing a promising therapeutic avenue to mitigate the consequences of brain injuries in youth.