A Balancing Act: The Immune System Supports Neurodegeneration and Neurogenesis.

Decapod crustaceans, like mammals, retain the ability to make new neurons throughout life. In mammals, immune cells are closely associated with stem cells that generate adult-born neurons. In crayfish, evidence suggests that immune cells (hemocytes) originating in the immune system travel to neurogenic regions and transform into neural progenitor cells. This nontraditional immune activity takes place continuously under normal physiological conditions, but little is known under pathological conditions (neurodegeneration). In this study, the immune system and its relationship with neurogenesis were investigated during neurodegeneration (unilateral antennular ablation) in adult crayfish. Our experiments show that after ablation (1) Proliferating cells decrease in neurogenic areas of the adult crayfish brain; (2) The immune response, but not neurogenesis, is ablation-side dependent; (3) Inducible nitric oxide synthase (iNOS) plays a crucial role in the neurogenic niche containing neural progenitors during the immune response; (4) Brain areas targeted by antennular projections respond acutely (15 min) to the lesion, increasing the number of local immune cells; (5) Immune cells are recruited to the area surrounding the ipsilateral neurogenic niche; and (6) The vasculature in the niche responds acutely by dilation and possibly also neovascularization. We conclude that immune cells are important in both neurodegeneration and neurogenesis by contributing in physiological conditions to the maintenance of the number of neural precursor cells in the neurogenic niche (neurogenesis), and in pathological conditions (neurodegeneration) by coordinating NO release and vascular responses associated with the neurogenic niche. Our data suggest that neural damage and recovery participate in a balance between these competing immune cell roles.

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.

Immunological regulation of neurogenic niches in the adult brain.

In mammals, neurogenesis and oligodendrogenesis are germinal processes that occur in the adult brain throughout life. The subventricular zone (SVZ) and subgranular zone (SGZ) are the main neurogenic regions in the adult brain. Therein, resides a subpopulation of astrocytes that act as neural stem cells (NSCs). Increasing evidence indicates that pro-inflammatory and other immunological mediators are important regulators of neural precursors into the SVZ and the SGZ. There are a number of inflammatory cytokines that regulate the function of NSCs. Some of the most studied include: interleukin-1, interleukin-6, tumor necrosis factor alpha, insulin-like growth factor-1, growth-regulated oncogene-alpha, leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, interferon-gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha. This plethora of immunological mediators can control the migration, proliferation, quiescence, cell-fate choices and survival of NSCs and their progeny. Thus, systemic or local inflammatory processes represent important regulators of germinal niches in the adult brain. In this review, we summarized the current evidence regarding the effects of pro-inflammatory cytokines involved in the regulation of adult NSCs under in vitro and in vivo conditions. Additionally, we described the role of proinflammatory cytokines in neurodegenerative diseases and some therapeutical approaches for the immunomodulation of neural progenitor cells.