Chronic peripheral inflammation, hippocampal neurogenesis, and behavior

Abstract

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.

Excess maternal fructose consumption impairs hippocampal function in offspring via epigenetic modification of BDNF promoter

“…We observed impaired adult hippocampal neurogenesis and hippocampal function in the offspring of fructose‐fed dams. Previous studies have demonstrated that neurogenesis is negatively regulated by inflammation and apoptosis (23, 24); however, in the present study, attenuated levels of neurogenesis did not seem to occur as a result of the influence of cytokines or apoptosis. Therefore, the observed decreases in hippocampal function may have been a result of decreases in neurogenesis.…”

“…Research has demonstrated that exposure to adversity in early life-specifically, environmental stress, under-or malnutrition, and infection-leads to lifelong alterations in hippocampal-related cognitive functions, at least in part via changes in hippocampal neurogenesis (22). Such decreases in hippocampal neurogenesis may be explained by several processes, including inflammation, apoptosis, and reduced levels of neurotrophic factors (23)(24)(25).…”

Neonatal systemic inflammation and the risk of low scores on measures of reading and mathematics achievement at age 10 years among children born extremely preterm

“…However, children who survived sepsis-associated encephalopathy perform less well after than they did previously (Kaur et al, 2016), Prolonged neonatal medical treatment, especially with mechanical ventilation, which appears to increase the risk of systemic inflammation (Bose et al, 2013), has been associated with specific impairments in mathematic tasks (Jaekel et al, 2014). Also, studies that provoked inflammation in adult rodents (Rogers, 1995;Chesnokova et al, 2016;Ryan and Nolan, 2016), and reports about adults with systemic inflammation (Hong and Banks, 2015;Wardill et al, 2016) support the view that concurrent or very recent inflammation impairs learning (Donzis and Tronson, 2014).…”

Parallel Effects of Methamphetamine on Anxiety and CCL3 in Humans and a Genetic Mouse Model of High Methamphetamine Intake

“…Brains were rapidly removed, and hippocampi were microdissected and frozen at −80°C until used. The hippocampus was chosen because of its demonstrated roles in affective behavior [24] and memory [25]. Brain tissue was homogenized in TRIzol and then pelleted.…”