Chronic peripheral inflammation, hippocampal neurogenesis, and behavior

- Chronic systemic illnesses, metabolic disorders, and aging create a state of chronic peripheral inflammation.
- Pro-inflammatory cytokines produced in the periphery communicate with the brain and activate resident microglia.
- Activated microglia locally release pro-inflammatory cytokines that disrupt hippocampal neurogenesis.
- Disruption of hippocampal neurogenesis might underlie the cognitive impairment, learning deficits, and mood disorders observed in patients with chronic inflammatory conditions.
- Disruption of hippocampal neurogenesis might also contribute to behavioral disturbances that occur in aging patients.

Adult hippocampal neurogenesis is involved in memory and learning, and disrupted neurogenesis is implicated in cognitive impairment and mood disorders, including anxiety and depression. Some long-term peripheral illnesses and metabolic disorders, as well as normal aging, create a state of chronic peripheral inflammation. These conditions are associated with behavioral disturbances linked to disrupted adult hippocampal neurogenesis, such as cognitive impairment, deficits in learning and memory, and depression and anxiety. Pro-inflammatory cytokines released in the periphery are involved in peripheral immune system-to-brain communication by activating resident microglia in the brain. Activated microglia reduce neurogenesis by suppressing neuronal stem cell proliferation, increasing apoptosis of neuronal progenitor cells, and decreasing survival of newly developing neurons and their integration into existing neuronal circuits. In this review, we summarize evolving evidence that the state of chronic peripheral inflammation reduces adult hippocampal neurogenesis, which, in turn, produces the behavioral disturbances observed in chronic inflammatory disorders. As there are no data available on neurogenesis in humans with chronic peripheral inflammatory disease, we focus on animal models and, in parallel, consider the evidence of cognitive disturbance and mood disorders in human patients.