RESUMEN
Sports-related concussions are particularly common during adolescence, and there is insufficient knowledge about how recurrent concussions in this phase of life alter the metabolism of essential structures for memory in adulthood. In this sense, our experimental data revealed that seven recurrent concussions (RC) in 35-day-old rats decreased short-term and long-term memory in the object recognition test (ORT) 30 days after injury. The RC protocol did not alter motor and anxious behavior and the immunoreactivity of brain-derived neurotrophic factor (BDNF) in the cerebral cortex. Recurrent concussions induced the inflammatory/oxidative stress characterized here by increased glial fibrillary acidic protein (GFAP), interleukin 1ß (IL 1ß), 4-hydroxynonenal (4 HNE), protein carbonyl immunoreactivity, and 2',7'-dichlorofluorescein diacetate oxidation (DCFH) levels and lower total antioxidant capacity (TAC). Inhibited Na+,K+-ATPase activity (specifically isoform α2/3) followed by Km (Michaelis-Menten constant) for increased ATP levels and decreased immunodetection of alpha subunit of this enzyme, suggesting that cognitive impairment after RC is caused by the inability of surviving neurons to maintain ionic gradients in selected targets to inflammatory/oxidative damage, such as Na,K-ATPase activity.
Asunto(s)
Conmoción Encefálica , Disfunción Cognitiva , Hipocampo , Trastornos de la Memoria , Enfermedades Neuroinflamatorias , Estrés Oxidativo/fisiología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Memoria Espacial/fisiología , Factores de Edad , Animales , Conmoción Encefálica/complicaciones , Conmoción Encefálica/inmunología , Conmoción Encefálica/metabolismo , Conmoción Encefálica/fisiopatología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/inmunología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Modelos Animales de Enfermedad , Hipocampo/inmunología , Hipocampo/metabolismo , Hipocampo/fisiopatología , Masculino , Trastornos de la Memoria/etiología , Trastornos de la Memoria/inmunología , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/fisiopatología , Enfermedades Neuroinflamatorias/etiología , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/fisiopatología , Ratas , Ratas WistarRESUMEN
Traumatic brain injury (TBI) is a public health problem in which even though 80 to 90% of cases are considered mild, usually starts a sequence of neurological disorders that can last a considerable time. Most of the research of this injury has been focused on oxidative stress and functional deficits; however, mechanisms that underlie the development of neuropsychiatric disorders remain little researched. Due to this, the present authors decided to investigate whether recurrent concussion protocols alter depressive-like phenotype behavior, and whether mitochondria play an indispensable role in this behavior or not. The experimental data revealed, for the first time, that the present protocol of recurrent concussions (4, 7, and 10 injuries) in mice did not alter immobility time during tail suspension tests (TSTs), but decreased hippocampal mitochondrial respiration and increased expression of proteins such as nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide (SOD2). This experimental data suggests that bioenergetic changes elicited by recurrent concussion did not induce depressive-like behavior, but activated the transcription factor of responsive antioxidant elements (ARE) that delay or prevent secondary cascades in this neurological disease.