Impaired interleukin‐1 signaling is associated with deficits in hippocampal memory processes and neural plasticity

Abstract

ABSTRACT:The cytokine interleukin-1 (IL-1) is produced by peripheral immune cells as well as glia and neurons within the brain; it plays a major role in immune to brain communication and in modulation of neural, neuroendocrine, and behavioral systems during illness. Although previous studies demonstrated that excess levels of IL-1 impaired memory processes and neural plasticity, it has been suggested that physiological levels of IL-1 are involved in hippocampal-dependent memory and long-term potentiation (LTP). To examine this hypothesis, we studied IL-1 receptor type I knockout (IL-1rKO) mice in several paradigms of memory function and hippocampal plasticity. In the spatial version of the water maze test, IL-1rKO mice displayed significantly longer latency to reach a hidden platform, compared with wild-type controls. Furthermore, IL-1rKO exhibited diminished contextual fear conditioning. In contrast, IL-1rKO mice were similar to control animals in hippocampal-independent memory tasks; i.e., their performance in the visually guided task of the water maze and the auditory-cued fear conditioning was normal. Electrophysiologically, anesthetized IL-1rKO mice exhibited enhanced paired-pulse inhibition in response to perforant path stimulation and no LTP in the dentate gyrus. In vitro, decreased paired-pulse responses, as well as a complete absence of LTP, were observed in the CA1 region of hippocampal slices taken from IL-1rKO mice compared with WT controls. These results suggest that IL-1 contributes to the regulation of memory processes as well as short-and long-term plasticity within the hippocampus. These findings have important implications to several conditions in humans, which are associated with long-term defects in IL-1 signaling, such as mutations in the IL-1 receptor accessory protein-like gene, which are involved in a frequent form of X-linked mental retardation.

Three Promoters Regulate Tissue- and Cell Type-specific Expression of Murine Interleukin-1 Receptor Type I

“…The expression of P3-IL-1R1 in dentate gyrus is interesting because this suggests that IL-1R1 expression in neurons in this region may be controlled differently from other cell types that are involved in IL-1-mediated inflammatory processes. This is consistent with the fact that stimulation of neurons in the brain by IL-1 is not known to produce inflammatory processes but modulates learning and memory by affecting long term potentiation in hippocampal neurons (31). It is of interest to note that a CREB-binding site is only found in CP3.…”

Interactions between NF-κB and SP3 Connect Inflammatory Signaling with Reduced FGF-10 Expression

“…An emerging body of literature also implicates NF-B in regulating neural repair and neural synapse integrity. NF-B influences neuronal excitability in the amygdala, protecting neurons in this critical region of the brain from excitoxicity while simultaneously promoting long term potentiation (51,52). NF-B has also been implicated in promoting neural regeneration and neural synapse pruning in the hippocampus (52)(53)(54)(55).…”

Differential gene expression profiling of large and small retinal ganglion cells

“…This corroborates well with topologically proximal Ccr5-interlinked endogenous chemokines on the network, which are now being increasingly suggested to play physiological roles in synaptic function and plasticity (Tonelli et. al., 2005) and in hippocampal-dependent memory and long-term potentiation (Avital et. al., 2003;Ross et.…”