The detrimental effects of lipopolysaccharide-induced neuroinflammation on adult hippocampal neurogenesis depend on the duration of the pro-inflammatory response
Martha Pérez-Domínguez
Evangelina ávila-Mu?oz
Eduardo Domínguez-Rivas
Angélica Zepeda
摘要：Adult hippocampal neurogenesis is a finely tuned process regulated by extrinsic factors. Neuroinflamma-tion is a hallmark of several pathological conditions underlying dysregulation of neurogenesis. In animal models, lipopolysaccharide (LPS)-induced neuroinflammation leads to a neurogenic decrease mainly asso-ciated to the early inflammatory response. However, it is not well understood how the neuroinflammatory response progresses over time and if neurogenesis continues to be diminished during the late neuroin-flammatory response. Moreover, it is unknown if repeated intermittent administration of LPS along time induces a greater reduction in neurogenesis. We administered one single intraperitoneal injection of LPS or saline or four repeated injections (one per week) of LPS or saline to young-adult mice. A cohort of new cells was labeled with three 5-bromo-2-deoxyuridine injections (one per day) 4 days after the last LPS in-jection. We evaluated systemic and neuroinflammation-associated parameters and compared the effects of the late neuroinflammatory response on neurogenesis induced by each protocol. Our results show that 1) a single LPS injection leads to a late pro-inflammatory response characterized by microglial activation, moderate astrocytic reaction and increased interleukin-6 levels. This response correlates in time with de-creased neurogenesis and 2) a repeated intermittent injection of LPS does not elicit a late pro-inflammatory response although activated microglia persists. The latter profile is not accompanied by a continued long-term hippocampal neurogenic decrease. Hereby, we provide evidence that the neuroinflammatory response is a dynamic process that progresses in a milieu-dependent manner and does not necessarily lead to a neu-rogenic decrease, highlighting the complex interaction between the immune system and neurogenesis.
机标关键词：
分类号：R453(治疗学)R392(医学免疫学)Q2(细胞生物学)
论文发表日期：2019-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 817-825 )
英文信息