A Common Language: How Neuroimmunological Cross Talk Regulates Adult Hippocampal Neurogenesis

Abstract

Immune regulation of the brain is generally studied in the context of injury or disease. Less is known about how the immune system regulates the brain during normal brain function. Recent work has redefined the field of neuroimmunology and, as long as their recruitment and activation are well regulated, immune cells are now known to have protective properties within the central nervous system in maintaining brain health. Adult neurogenesis, the process of new neuron generation in the adult brain, is highly plastic and regulated by diverse extrinsic and intrinsic cues. Emerging research has shown that immune cells and their secreted factors can influence adult neurogenesis, both under baseline conditions and during conditions known to change neurogenesis levels, such as aging and learning in an enriched environment. This review will discuss how, under nonpathological conditions, the immune system can interact with the neural stem cells to regulate adult neurogenesis with particular focus on the hippocampus-a region crucial for learning and memory.

Figure 1

Neural progenitor cells and immune cells coexist in the hippocampal neurogenic niche. Type 1 neural stem cells in the subgranular zone of the hippocampal dentate gyrus mature through different developmental stages during the multistep process of new neuron formation. Type 1 radial glia-like cells give rise to transiently amplifying progenitor cells (Type 2a/Type 2b). After passing the neuronally committed Type 3 stage the cells become postmitotic after which they integrate as mature granule cells into the existing hippocampal circuitry. Within the complex niche environment peripheral and resident immune cells interact with niche cells to regulate the neurogenic process under physiological conditions. In addition, immune cells in the blood and the niche secrete immune molecules, including cytokines and chemokines, to facilitate neuroimmunological communication.