NF-kB (Nuclear factor kappa B) su relación con aprendizaje, memoria y neurogénesis en el hipocampo / NF-kB (nuclear factor NF-kB) its relationship with learning, memory and neurogenesis in the hippocampus

En esta revisión bibliográfica focalizaremos sobre la importancia del factor de transcripción NF-kB en el sistema nervioso. NF-kB es una familia de factores de transcripción, conservada evolutivamente, involucrada en los mecanismos básicos celulares de la respuesta inmune, la inflamación, el desarrollo y la apoptosis, que también se expresa en el sistema nervioso central, especialmente en las áreas implicadas en el procesamiento de la memoria, y es activado por señales como el glutamato y el Ca2+. En los últimos años, numerosas investigaciones han comprobado su rol fundamental como parte de la vía de señalización en la regulación de la expresión de genes implicados en la memoria de largo término. Se comprobó la importancia del NF-kB en el neurodesarrollo, en la regulación de la supervivencia neuronal y de la neurogénesis en el hipocampo del adulto. También se comprobó un aumento de la actividad del NF-kB en el cerebro en modelos animales de depresión. Este efecto estaría mediado por el incremento de la IL-6, proinflamatoria. En el modelo de depresión de oscuridad constante también se observaron alteraciones en los niveles de las proteínas hipocampales per2 y npas2, vinculadas al ritmo circadiano. El conocimiento de la neurobiología de este factor de transcripción nos permitirá vislumbrar sus potenciales implicaciones clínicas, así como la posibilidad de influir farmacológicamente: en las memorias traumáticas, en la declinación cognitiva y en los trastornos del ánimo.

In this literature review, we will focus on the importance of the transcription factor NF-kB in the nervous system. NF-kB is a transcription factor family, evolutionarily conserved, which is involved in the basic mechanisms involved in the cellular immune response, inflammation, development and apoptosis, which is also expressed in the Central Nervous System, especially in the areas involved in the processing of memory, and it is activated by signals such as glutamate and Ca2+. In recent years, numerous studies have proven its key role as part of the signaling path in the regulation of the expression of genes in the long-term memory. The importance of NF-kB in neurodevelopment has also been verified in relation to the regulation of neuronal survibal and the neurogenesis in the adult hippocampus. An increase in the NF-kB activity in the brain has also been found in animal models of depression. This effect would be mediated by an increase in pro-inflammatory IL-6. In the model of Constant Drkness Depression, an alteration of the hippocampal protein levels per2 and npas2 linked to circadian rhythm was also observed. Knowing the neurobiology of this transcription factor will allow us to glimpse their potential clinical implications, and the possibility to influence pharmacologically in traumatic memories, in cognitive decline, and mood disorders.

Amifostine ameliorates recognition memory defect in acute radiation syndrome caused by relatively low-dose of gamma radiation

This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.