Impaired Interleukin-1β and c-Fos Expression in the Hippocampus Is Associated with a Spatial Memory Deficit in P2X7 Receptor-Deficient Mice

Abstract

Recent evidence suggests that interleukin-1β (IL-1β), which was originally identified as a proinflammatory cytokine, is also required in the brain for memory processes. We have previously shown that IL-1β synthesis in the hippocampus is dependent on P2X7 receptor (P2X7R), which is an ionotropic receptor of ATP. To substantiate the role of P2X7R in both brain IL-1β expression and memory processes, we examined the induction of IL-1β mRNA expression in the hippocampus of wild-type (WT) and homozygous P2X7 receptor knockout mice (P2X7R−/−) following a spatial memory task. The spatial recognition task induced both IL-1β mRNA expression and c-Fos protein activation in the hippocampus of WT but not of P2X7R−/− mice. Remarkably, P2X7R−/− mice displayed spatial memory impairment in a hippocampal-dependant task, while their performances in an object recognition task were unaltered. Taken together, our results show that P2X7R plays a critical role in spatial memory processes and the associated hippocampal IL-1β mRNA synthesis and c-Fos activation.

Immune dysregulation and cognitive vulnerability in the aging brain: Interactions of microglia, IL-1β, BDNF and synaptic plasticity

“…In a health brain, in the absence of injury or infection, levels of IL-1β are generally low, but they are upregulated by contextual fear learning (Goshen et al, 2007), and spontaneous spatial recognition in the Y-maze paradigm (Labrousse et al, 2009). Conversely, contextual memory is impaired by genetic reduction of endogenous IL-1β signaling (Azouz et al, 1996; Goshen et al, 2007).…”

Microglia in neuronal plasticity: Influence of stress

“…Under normal conditions, IL-1b has been largely described as an important factor involved in memory process. Even if brain levels of IL-1b under homeostatic conditions are very low, increased levels were found in the hippocampus after hippocampal-dependent contextual learning and spontaneous spatial recognition (Goshen et al, 2007;Labrousse et al, 2009). Interestingly, mice deficient in IL-1b signaling do not present this increase of IL-1b expression after fear conditioning and show impaired fear memory and also spatial memory (Avital et al, 2003;Goshen et al, 2007;Goshen and Yirmiya, 2009).…”

Cytokines neuroinflammatory reaction to the action of homoaggregatic and liposomal forms of b-amyloid 1-40 in rats

“…Известно, что цитокины и их рецепторы присутствуют во многих структурах головного мозга, в том числе в коре больших полушарий и гиппокампе, где они выполняют функции межклеточных медиаторов ЦНС [28]. Недавно появилось сообщение, что Аb40 также имеет непосредственное отношение к врождённому иммунитету [29].…”