Glial PAMPering and DAMPening of Adult Hippocampal Neurogenesis

Abstract

Adult neurogenesis represents a mature brain’s capacity to integrate newly generated neurons into functional circuits. Impairment of neurogenesis contributes to the pathophysiology of various mood and cognitive disorders such as depression and Alzheimer’s Disease. The hippocampal neurogenic niche hosts neural progenitors, glia, and vasculature, which all respond to intrinsic and environmental cues, helping determine their current state and ultimate fate. In this article we focus on the major immune communication pathways and mechanisms through which glial cells sense, interact with, and modulate the neurogenic niche. We pay particular attention to those related to the sensing of and response to innate immune danger signals. Receptors for danger signals were first discovered as a critical component of the innate immune system response to pathogens but are now also recognized to play a crucial role in modulating non-pathogenic sterile inflammation. In the neurogenic niche, viable, stressed, apoptotic, and dying cells can activate danger responses in neuroimmune cells, resulting in neuroprotection or neurotoxicity. Through these mechanisms glial cells can influence hippocampal stem cell fate, survival, neuronal maturation, and integration. Depending on the context, such responses may be appropriate and on-target, as in the case of learning-associated synaptic pruning, or excessive and off-target, as in neurodegenerative disorders.

Microglia-Mediated Inflammation and Neural Stem Cell Differentiation in Alzheimer’s Disease: Possible Therapeutic Role of KV1.3 Channel Blockade

“…As mentioned, impaired CX3CR1 has been described in AD ( Guedes et al, 2018 ). In the hippocampus, this impairment has been linked to adult hippocampal neurogenesis disruption, with spatial and fear-memory and motor learning loss due mainly to the increase of IL-1 β by microglial activation ( Parkitny and Maletic-Savatic, 2021 ). Remarkably, the importance of IL-1 β in adult hippocampal neurogenesis was recognized over a decade ago when it was associated with anti-proliferative and anti-neurogenic effects ( Crampton et al, 2012 ).…”

“…Remarkably, the importance of IL-1 β in adult hippocampal neurogenesis was recognized over a decade ago when it was associated with anti-proliferative and anti-neurogenic effects ( Crampton et al, 2012 ). Moreover, PRR seem to be implicated in the modulation of adult neurogenesis as they are expressed also in neural progenitor cells (NPCs), providing communication pathways from apoptotic or injured cells ( Parkitny and Maletic-Savatic, 2021 ).…”

Melatonin Prevents Depression but Not Anxiety-like Behavior Produced by the Chemotherapeutic Agent Temozolomide: Implication of Doublecortin Cells and Hilar Oligodendrocytes

“…For instance, MEL increases cell proliferation, cell survival, neuronal differentiation, and the axons of new and old neurons but also modulates microglia [14][15][16]. In addition, other studies have proven the capability of MEL to regulate oligodendrocytes, cells relevant for the myelination of axons, as well as the modulation of neuronal function, and to provide neuronal trophic support through the production of soluble factors in the neurogenic niche of the DG in the hippocampus [12,22,23]. Here, we analyzed the short-and long-term effects of TMZ on cell proliferation and intermediate stages of the neurogenic process in the DG of the hippocampus.…”