A pivotal role for interleukin-4 in atorvastatin-associated neuroprotection in rat brain.

Inflammatory changes, characterized by an increase in pro-inflammatory cytokine production and up-regulation of the corresponding signaling pathways, have been described in the brains of aged rats and rats treated with the potent immune modulatory molecule lipopolysaccharide (LPS). These changes have been coupled with a deficit in long-term potentiation (LTP) in hippocampus. The evidence suggests that anti-inflammatory agents, which attenuate the LPS-induced and age-associated increase in hippocampal interleukin-1beta (IL-1beta) concentration, lead to restoration of LTP.

Interleukin-4 mediates the neuroprotective effects of rosiglitazone in the aged brain.

Increased expression of proinflammatory cytokines, like interleukin-1 beta (IL-1 beta), is a feature of the aged brain and it is generally accepted that the primary cell source of these cytokines is activated microglia. In hippocampus of aged rats, the increase in IL-1 beta is accompanied by microglial activation and impaired long-term potentiation (LTP). Peroxisome proliferator-activated receptors (PPARs) possess anti-inflammatory properties that target microglia.

IL-4 attenuates the neuroinflammation induced by amyloid-beta in vivo and in vitro.

It has been shown that Abeta inhibits long-term potentiation (LTP) in the rat hippocampus and this is accompanied by an increase in hippocampal concentration of IL-1beta. Abeta also increases microglial activation, which is the likely cell source of IL-1beta. Because IL-4 attenuates the effects of IL-1beta in hippocampus, and microglial activation is inhibited by minocycline, we assessed the ability of both IL-4 and minocycline to modulate the effects of Abeta on LTP and IL-1beta concentration.

The HMG-CoA reductase inhibitor, atorvastatin, attenuates the effects of acute administration of amyloid-beta1-42 in the rat hippocampus in vivo.

One response of the brain to stressors is to increase microglial activation with the consequent production of proinflammatory cytokines like interleukin-1beta (IL-1beta), which has been shown to exert an inhibitory effect on long-term potentiation (LTP) in the hippocampus. It has been consistently shown, particularly in vitro, that amyloid-beta (Abeta) peptides increase activation of microglia, while its inhibitory effect on LTP is well documented, and associated with the Abeta-induced increase in IL-1beta. Here we set out to establish whether the Abeta-induced inhibition of LTP in perforant path-granule cell synapses, was coupled with evidence of microglial activation and to assess whether atorvastatin, which is used primarily in the treatment of hyperlipidaemia but which possesses anti-inflammatory properties, might modulate the effect of Abeta on LTP.

Eicosapentaenoic acid confers neuroprotection in the amyloid-beta challenged aged hippocampus.

Among the changes that occur in the hippocampus with age, is a deficit in long-term potentiation (LTP). This impairment is associated with inflammatory changes, which are typified by increased concentration of the pro-inflammatory cytokine interleukin-1beta (IL-1beta). Activated microglia are the most likely cell source of IL-1beta, but data demonstrating an age-related increase in microglial activation is equivocal.

Interaction between interferon gamma and insulin-like growth factor-1 in hippocampus impacts on the ability of rats to sustain long-term potentiation.

There is compelling evidence to suggest that inflammation significantly contributes to neurodegenerative changes. Consistent with this is the observation that several neurodegenerative disorders are accompanied by an increase in the concentration of interleukin (IL)-1beta. IL-1beta has a negative impact on synaptic plasticity and therefore an increased concentration of IL-1beta, such as that in the hippocampus of the aged rat, is associated with a deficit in long-term potentiation (LTP).

Activation of c-Jun-N-terminal kinase is critical in mediating lipopolysaccharide-induced changes in the rat hippocampus.

Lipopolysaccharide (LPS) exerts a myriad of effects in rat hippocampus; it increases the concentration of the proinflammatory cytokine, interleukin-1beta (IL-1beta), and signalling via the IL-1 type I receptor (IL-1RI) resulting in phosphorylation of the stress-activated protein kinase, c-jun-N-terminal kinase (JNK) and impairment in long-term potentiation (LTP). This study was designed to establish whether activation of JNK is a pivotal event in mediating the effects of LPS in hippocampus and therefore LPS-treated rats were injected intracerebroventricularly with saline, the JNK inhibitor D-JNKI1, or with the anti-inflammatory cytokine IL-4, which antagonizes the effects of IL-1beta upstream of JNK activation. We report that IL-4 blocked the LPS-induced increase in IL-1RI expression and associated increases in phosphorylation of JNK and c-jun, whereas D-JNKI1 inhibited the LPS-induced phosphorylation of c-jun.

Role of interleukin-4 in regulation of age-related inflammatory changes in the hippocampus.

It is well documented that long term potentiation (LTP) is impaired in the hippocampus of the aged animal. Among the changes that contribute to this impairment is an increase in hippocampal concentration of the pro-inflammatory cytokine interleukin-1beta (IL-1beta), and increased IL-1beta-induced signaling. In this study we investigated the possibility that these changes were a consequence of decreased concentration of the anti-inflammatory cytokine, IL-4, and decreased IL-4-stimulated signaling.