Vaccination reduces central nervous system IL-1ß and memory deficits after COVID-19 in mice.

Up to 25% of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit postacute cognitive sequelae. Although millions of cases of coronavirus disease 2019 (COVID-19)-mediated memory dysfunction are accumulating worldwide, the underlying mechanisms and how vaccination lowers risk are unknown. Interleukin-1 (IL-1), a key component of innate immune defense against SARS-CoV-2 infection, is elevated in the hippocampi of individuals with COVID-19. Here we show that intranasal infection of C57BL/6J mice with SARS-CoV-2 Beta variant leads to central nervous system infiltration of Ly6Chi monocytes and microglial activation. Accordingly, SARS-CoV-2, but not H1N1 influenza virus, increases levels of brain IL-1ß and induces persistent IL-1R1-mediated loss of hippocampal neurogenesis, which promotes postacute cognitive deficits. Vaccination with a low dose of adenoviral-vectored spike protein prevents hippocampal production of IL-1ß during breakthrough SARS-CoV-2 infection, loss of neurogenesis and subsequent memory deficits. Our study identifies IL-1ß as one potential mechanism driving SARS-CoV-2-induced cognitive impairment in a new mouse model that is prevented by vaccination.

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.