Enduring consequences of early-life infection on glial and neural cell genesis within cognitive regions of the brain

Abstract

Systemic infection with Escherichia coli on postnatal day (P) 4 in rats results in significantly altered brain cytokine responses and behavioral changes in adulthood, but only in response to a subsequent immune challenge with lipopolysaccharide [LPS]. The basis for these changes may be long-term changes in glial cell function. We assessed glial and neural cell genesis in the hippocampus, parietal cortex (PAR), and pre-frontal cortex (PFC), in neonates just after the infection, as well as in adulthood in response to LPS. E. coli increased the number of newborn microglia within the hippocampus and PAR compared to controls. The total number of microglia was also significantly increased in E. coli-treated pups, with a concomitant decrease in total proliferation. On P33, there were large decreases in numbers of cells coexpressing BrdU and NeuN in all brain regions of E. coli rats compared to controls. In adulthood, basal neurogenesis within the dentate gyrus (DG) did not differ between groups; however, in response to LPS, there was a decrease in neurogenesis in early-infected rats, but an increase in controls to the same challenge. There were also significantly more microglia in the adult DG of early-infected rats, although microglial proliferation in response to LPS was increased in controls. Taken together, we have provided evidence that systemic infection with E. coli early in life has significant, enduring consequences for brain development and subsequent adult function. These changes include marked alterations in glia, as well as influences on neurogenesis in brain regions important for cognition.

Ontogenetic immune challenges shape adult personality in mallard ducks

“…Although a comprehensive understanding of the neurological basis of personality expression is currently lacking, it is plausible that changes in brain physiology or structure at different stages of development could affect personality. Immune challenges can affect multiple aspects of neural physiology and structure, including neurogenesis [27], synthesis of proinflammatory cytokine [65] or transcription factors [66] in the brain, and modification of the hypothalamic-pituitary-adrenal axis [28]. Alterations to these processes at different developmental stages may have differential effects; thus, differences between birds that were immune-challenged at different ages may be mechanistically linked to age-specific patterns of neural development.…”

“…sickness behaviours that cease post-disease recovery), but may instead lead to long-lasting behavioural effects, especially if challenges occur during early, sensitive periods of life. In rodents, recent studies have demonstrated the importance of neonatal immune challenges in shaping adult brain structure [27], immune response [28] and exploratory behaviour [29]. However, questions remain regarding the importance of the timing (i.e.…”

Regulation of Adult Neurogenesis and Plasticity by (Early) Stress, Glucocorticoids, and Inflammation

“…Under physiological conditions, microglia show a ramified phenotype involved in homeostasis of brain functioning, and associated with the production of anti-inflammatory and neurotrophic factors. When primed, by ELS or challenged by pathogens or damaged during adult life, microglia can switch to an amoeboid phenotype thereby gaining macrophage-like properties, including phagocytosis of tissue debris, as well as initiation of tissue repair or rather produce cytokines that are detrimental for neuronal function and viability (Bilbo et al 2007;Bilbo and Schwarz 2009;Bland et al 2010).…”

“…Finally, it is important to mention that levels of neurogenesis are permanently affected also by other ELS not necessarily related to the mother-infant interaction alone. For example, ELS inflammation (Jakubs et al 2008;Musaelyan et al 2014), radiation therapy (Fukuda et al 2005;Naylor et al 2008;Hoffman and Yock 2009), anesthesia (Zhu et al 2010), stroke (Spadafora et al 2010), infection (Bland et al 2010), and ethanol exposure (Singh et al 2009) induce long-lasting effects on neurogenesis associated with late-onset cognitive impairment. Thus, the studies described have shown that EL experiences during both pre-and postnatal development can bidirectionally alter hippocampal neuronal plasticity and synaptic integrity.…”

Early-life enteric infections: relation between chronic systemic inflammation and poor cognition in children

“…104,105 Rotavirus infection can potentially affect the central nervous system in pediatric patients, 106 although the long-term impacts of this infection are unknown. In rodent models, systemic infection or LPS exposure during the postnatal period affects brain development and function in adulthood, 107,108 signifying both pathogens and commensal organisms as contributing factors.…”