A large number of studies indicate the role of early-life experience, in particular neonatal infections, in the formation of a high level of anxiety later in life. Changes in NMDA and AMPA glutamate receptor subunit composition that result in the violation of receptor functional activity may comprise the mechanism behind the behavioral impairments. Our work aimed to investigate exploratory and anxiety-like forms of behavior of adult rats that were treated with lipopolysaccharide (LPS) during the 3rd week of postnatal development at neuroinflammation-inducing doses. Levels of gene expression of NMDA receptor subunits (Grin1, Grin2a, Grin2b) and AMPA receptor subunits (Gria1, Gria2) in the medial prefrontal cortex, ventral and dorsal areas of the hippocampus were assessed by qRT-PCR. Our study on Wistar male rats revealed that the administration of LPS at doses of 25 and 50 μg/kg on P15, P18, P21 increased the expression of proinflammatory cytokine mRNA (interleukin-1β and tumor necrosis factor) in the hippocampus 2 h post treatment. Elevated expression of Grin2b, Gria1, Gria2 genes in the ventral hippocampus was observed 3 months after the administration of 50 μg/kg LPS compared with saline-treated control rats. Gria2 gene expression was found to be increased in the dorsal hippocampus 3 months after 25 μg/kg LPS injections in comparison with the controls. These changes were accompanied by impaired exploratory behavior of adult LPS-treated rats in the Open field test and a decreased level of anxiety in the Elevated plus maze. Taken together, our results substantiate early-life inflammation as a cause of prolonged changes in the hippocampal expression of genes of NMDA and AMPA receptor subunits and have an impact on related forms of behavior.

Temporal lobe epilepsy (TLE) is one of the most common and severe forms of epilepsy in humans; it is difficult to treat and is leading to the development of comorbid neuropsychiatric disorders. The possible role of glia and the associated neuroinflammation in the pathogenesis of this disease is currently under intensive investigation. The aim of the study was to analyze changes in the expression of pro-inflammatory cytokines genes interleukin-1β (Il1b) and tumor necrosis factor α (Tnfa) in various brain areas during the latent phase of the lithium-pilocarpine model of TLE. Status epilepticus was induced by injecting lithium chloride and pilocarpine hydrochloride to 7–8-week-old male Wistar rats. Control animals were injected with saline instead of pilocarpine. Experimental groups consisted of animals with short mild seizures and prolong severe convulsions based on the fact that spontaneous recurrent seizures in the chronic phase develop predominantly in rats that had severe long-term seizures after pilocarpine administration. Analysis of Il1b and Tnfa mRNA expression was performed by quantitative RT-PCR in the dorsal and ventral hippocampus, temporal, entorhinal and medial prefrontal cortex 7 days after the administration of pilocarpine. The mRNA expression of Il1b but not Tnfa has been shown to be upregulated in the hippocampus of animals with prolonged severe seizures. No changes were observed in the temporal and entorhinal cortex. These data indicate that Il1b is very likely to be involved in epileptogenesis. Thus, the results of our study suggest that interleukin-1 receptors may be a potential therapeutic target for the prevention of epileptogenesis.

Hypotheses relating to the developmental nature of cognitive impairments in schizophrenia and other neuropathologies propose that the development of stable cognitive deficit involves important roles for hypoxia, trauma, and infections operating during the prenatal and early postnatal periods. These pathological states are accompanied by increases in the production of proinflammatory cytokine interleukin-1β (IL-1β) in cells of the nervous and immune systems. We report here studies of the characteristics of the expression of the Fgf1 and Timp1 genes, which are involved in regulating the cerebral mechanisms of neuroplasticity, in cells of the medial prefrontal cortex and the dorsal and ventral areas of the hippocampus in adult rats given IL-1β during early postnatal ontogeny. Experiments were performed in standard conditions and on acquisition of a conditioned active avoidance reflex. Learning impairments in experimental animals were accompanied by decreased production of FGF-2 mRNA in cells of the medial prefrontal cortex and ventral hippocampus. There were no differences between groups in conditions without cognitive loading.

According to the Neurodevelopmental hypothesis, the long-lasting cognitive deficit in schizophrenia and other types of neuropathology may occur by injurious factors, such as hypoxia, traumas, infections that take place during pre- and postnatal development, at least at early stages. These pathological conditions are often associated with the high production of pro-inflammatory cytokine interleukin-1B (IL-1B) by the cells of immune and nervous systems. We investigated the expression of genes involved in the neuroplastic regulation (Fgf2 and Timp2) in medial prefrontal cortex and dorsal and ventral regions of hippocampus of adult rats that were treated with IL-1beta between P15 and P21. The learning impairment in IL-1beta-treated rats is accompanied by lower FGF-2 mRNA levels in medial prefrontal cortex and ventral (not dorsal) hippocampus, but TIMP-1 was not affected. No differences in TIMP-1 and FGF-2 mRNA expressions were observed in untrained IL-1beta-treated when compared to control rats.