Abstract
Infectious diseases in early postnatal ontogenesis often result in cognitive impairments, particularly learning and memory. The essential foundation of learning and memory is long-term synaptic plasticity, which depends on N-methyl-D-aspartate (NMDA) receptors. In the present study, bacterial infection was modeled by treating rat pups with bacterial lipopolysaccharide (LPS, 25 µg/kg) three times, during either the first or the third week of life. These time points are critical for the maturation of NMDA receptors. We assessed the effects of LPS treatments on the properties of long-term potentiation (LTP) in the CA1 hippocampus of young (21–23 days) and adolescent (51–55 days) rats. LTP magnitude was found to be significantly reduced in both groups of young rats, which also exhibited investigative and motor behavior disturbances in the open field test. No changes were observed in the main characteristics of synaptic transmission, although the LTP induction mechanism was disturbed. In rats treated with LPS during the third week, the NMDA-dependent form of LTP was completely suppressed, and LTP switched to the Type 1 metabotropic glutamate receptor (mGluR1)-dependent form. These impairments of synaptic plasticity and behavior were temporary. In adolescent rats, no difference was observed in LTP properties between the control and experimental groups. Lastly, the investigative and motor behavior parameters in both groups of adult rats were similar.
Highlights
Infectious diseases in early postnatal ontogenesis often result in impairments of cognitive functions, especially learning and memory, with central nervous system infections resulting in severe impairments of these functions in children [1]
The administration of low doses of LPS in rats in early postnatal ontogenesis induced the accumulation of interleukin 6 (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]
We found no difference in the AMPAR/NMDA receptor (NMDAR) ratios in evoked excitatory postsynaptic currents (eEPSCs) between the control and 3wLPS_y groups, suggesting, together with I/O data, that the NMDAR-mediated current is not diminished in experimental animals
Summary
Infectious diseases in early postnatal ontogenesis often result in impairments of cognitive functions, especially learning and memory, with central nervous system infections resulting in severe impairments of these functions in children [1]. According to the two-way repeated measures ANOVA, there were no changes in the PPR after the induction of LTP in any group of animals (Figure 1D) These results suggest that the postsynaptic locus of LTP expression in CA3-CA1 synapses is preserved in experimental animals. We compared the properties of synaptic NMDAR-mediated currents in CA1 hippocampal pyramidal neurons using voltage-clamp, whole-cell recordings in slices obtained from 3wLPS_y, and control animals (Figure 5). Previous studies showed persistent effects of postnatal systemic inflammatory challenges on escape learning in the footshock-elicited active avoidance and water maze paradigms [10]; other researchers observed long-lasting changes in NMDAR mRNA expression, which were associated with behavioral deficits [2] Differences in these behavioral results may be due to differences in experimental conditions. Control and experimental animals showed no difference in “easy” behavioral tests, such as open field or Y-maze tests; in more stressful tests, such as the water maze, differences between groups were observed, suggesting that animals exposed to LPS in early life periods may display altered susceptibility to stress in later life [2,10]
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