Neonatal proinflammatory stress induces accumulation of corticosterone and interleukin-6 in the hippocampus of juvenile rats: Potential mechanism of synaptic plasticity impairments

Abstract

Infectious diseases in early postnatal ontogenesis can induce neuroinflammation, disrupt normal central nervous system development, and contribute to pathogenesis of cerebral pathologies in adults. To study long-term consequences of such early stress, we induced neonatal proinflammatory stress (NPS) by injecting bacterial lipopolysaccharide into rat pups on postnatal days 3 and 5 and then assessed the levels of corticosterone, proinflammatory cytokines and their mRNAs, and neurotrophins and their mRNAs in the hippocampus and neocortex of the one-month-old animals. Long-term potentiation (LTP) was studied in hippocampal slices as an index of synaptic plasticity. NPS-induced impairments of LTP were accompanied by the accumulation of corticosterone and IL-6 in the hippocampus. In the neocortex, a decrease in exon IV BDNF mRNA was detected. We suggest that excessive corticosterone delivery to hippocampal receptors and proinflammatory changes persisting during brain maturation are among the principal molecular mechanisms responsible for NPS-induced neuroplasticity impairments.

Administration of Bacterial Lipopolysaccharide during Early Postnatal Ontogenesis Induces Transient Impairment of Long-Term Synaptic Plasticity Associated with Behavioral Abnormalities in Young Rats

“…In other studies, the repetitive administration of LPS in low doses induced a delayed decrease in LTP magnitude [8] and learning and memory deficits in rats [64]. The authors have shown that the gene expression levels of neurotrophic factor, BDNF, and its receptor, TrkB, were significantly decreased by LPS treatment, and glutamatergic transmission was attenuated in LPS-treated rats as well [8,64].…”

“…The alternative mechanism suggested by Iwai et al [60] is that induced IL-1b inhibits LTP via the activation of p38 MAPK and c-Jun N-terminal kinases (JNK) [61], and that these signal pathways inhibit AMPAR trafficking [62], which is an important mechanism of LTP induction [63]. In other studies, the repetitive administration of LPS in low doses induced a delayed decrease in LTP magnitude [8] and learning and memory deficits in rats [64]. The authors have shown that the gene expression levels of neurotrophic factor, BDNF, and its receptor, TrkB, were significantly decreased by LPS treatment, and glutamatergic transmission was attenuated in LPS-treated rats as well [8,64].…”

“…By binding to toll-like receptor 4, LPS promotes pro-inflammatory gene expression in the cells of the immune and nervous systems, including the expression of cytokines such as interleukin-1β (IL-1β), interleukin 6 (IL-6), or tumor necrosis factor alpha (TNF-α), as well as the Pharmaceuticals 2020, 13 decreased expression of transforming growth factor beta (TGF-β), a cytokine with immunosuppressive and anti-inflammatory properties [4][5][6][7]. The administration of low doses of LPS in rats in early postnatal ontogenesis induced the accumulation of IL-6 in the juvenile period [8]; and later, in adulthood, the same doses resulted in impaired behavior in the fear conditioning test [2], and in the Morris water maze [9,10]. Similarly, the administration of pro-inflammatory cytokines, such as IL-1β or TNF-α, led to impairments in the performance of passive and active avoidance tasks or long-term increases in anxiety, in addition to changes in investigative behavior, in adolescent and adult rats [11,12].…”

“…The essential foundation of learning and memory is synaptic plasticity [13,14]. As such, a disturbance in its properties due to inflammation might cause cognitive impairments [8]. Synaptic plasticity refers to the ability of chemical synapses to change their strength as a result of previous synaptic activation [15].…”

Prefrontal dopamine D1 receptor manipulation influences anxiety behavior and induces neuroinflammation within the hippocampus

“…Whereas anti-in ammatory agents primarily improved motivation and anxiety (Raison et al 2013). In addition, induction of depression-like behavior via learned helplessness paradigm resulted in an increased IL-6 expression within the hippocampus (Onufriev et al 2017). Ketamine's antidepressant effect might be through its ability to reduce cytokines in the hippocampus, thus functioning anti-in ammatory (Wang et al 2015).…”