Neonatal Escherichia coli infection alters glial, cytokine, and neuronal gene expression in response to acute amphetamine in adolescent rats

Abstract

Neonatal bacterial infection in rats alters the responses to a variety of subsequent challenges later in life. Here we explored the effects of neonatal bacterial infection on a subsequent drug challenge during adolescence, using administration of the psychostimulant amphetamine. Male rat pups were injected on postnatal day 4 (P4) with live Escherichia coli (E. coli) or PBS vehicle, and then received amphetamine (15 mg/kg) or saline on P40. Quantitative RT-PCR was performed on micropunches taken from medial prefrontal cortex, nucleus accumbens, and the CA1 subfield of the hippocampus. mRNA for glial and neuronal activation markers as well as pro-inflammatory and anti-inflammatory cytokines were assessed. Amphetamine produced brain region specific increases in many of these genes in PBS controls, while these effects were blunted or absent in neonatal E. coli treated rats. In contrast to the potentiating effect of neonatal E. coli on glial and cytokine responses to an immune challenge previously observed, neonatal E. coli infection attenuates glial and cytokine responses to an amphetamine challenge.

The HIV-1 transgenic rat model of neuroHIV

“…For example, there is strong evidence correlating early CNS infection with the development of schizophrenia (Suvisaari, Mautemps et al 2003). Infections early in life can alter cytokine expression and glial activation in response to a subsequent immune challenge in adulthood (Bland, Beckley et al 2010), and a neonatal Escherichia coli infection has been shown to impair memory formation in adulthood in the presence of a subsequent immune challenge with LPS (Bilbo and Schwarz 2009). …”

Perinatal exposure to air pollutants had adverse effects on behavioral outcomes in mice

“…Earlier work by Auten et al and preliminary data collected by the Bilbo lab found that exposure to air pollutants during the perinatal periods provoked an increase in cytokine expression in the fetal lung, brain, and placenta (33,34) .…”

The impact of early life immune challenge on behavior and microglia during postnatal development

“…Glial-neuronal signaling may also be a key mechanism that influences long-term changes following early immune challenge as postnatal exposure to E.coli infections has been shown to lead to immediate and long-term changes in microglia [35] . Certainly, microglia are emerging as a key regulator of CNS development and in particular, evidence is building that sex differences in microglia during early postnatal life may contribute to long-term sex differences in brain function.…”