Evidence That Increased Hippocampal Expression of the Cytokine Interleukin-1β Is a Common Trigger for Age- and Stress-Induced Impairments in Long-Term Potentiation

Abstract

Several cytokines and their receptors are identified in brain; one of these is the proinflammatory cytokine interleukin-1beta that is synthesized and released from neurons and glia in response to stress or insult. Among the actions of interleukin-1beta is its ability to inhibit long-term potentiation in the hippocampus in vitro, an action that mimics one of the consequences of stress and age. It has been shown that the concentration of interleukin-1beta in brain tissue is increased in neurodegenerative conditions, and recent evidence from our laboratory has indicated an increase in the concentration of interleukin-1beta in the hippocampus of aged rats. These observations led us to consider that the underlying common cause of impaired long-term potentiation in aged and stressed rats might be increased endogenous interleukin-1beta concentration in hippocampus. The data presented here indicate that there was an inverse relationship between concentration of interleukin-1beta in the dentate gyrus and long-term potentiation in perforant path-->granule cell synapses in aged rats, stressed rats, and rats pretreated with interleukin-1beta. The evidence suggested that the cytokine induces formation of reactive oxygen species that triggers lipid peroxidation in vivo, as well as in vitro, and that these changes lead to depletion of membrane arachidonic acid that correlates with impaired long-term potentiation. We propose that three theories of aging, the glucocorticoid theory, the membrane theory, and the free radical theory, constitute three facets of age with one underlying trigger: an increase in the endogenous concentration of interleukin-1beta in hippocampus.

The role of polyunsaturated fatty acids in restoring the aging neuronal membrane

“…[79]) This effect of the oxidative stress is Ca 2+ dependent [87,88,91,92,133,134]; a finding consistent with the fact that calcium inhibits synaptic plasticity. It is noteworthy that treatment with n-3 fatty acids can restore the LTP in aged rats [70,71,[77][78][79].…”

“…Prostaglandins enhance corticotropin-releasing factor (CRF) activity [10,67,116,121], and CRF induces release of prostaglandins [97]. Prostaglandins enhance thyrotropin-releasing hormone (TRH) release and stimulate the dopaminergic and noradrenergic receptor activity [88,123], while beta-endorphin inhibits prostaglandin synthesis [43].…”

Effects of 900MHz radiofrequency on corticosterone, emotional memory and neuroinflammation in middle-aged rats

“…These deficits include modified neurobiological parameters such as an increase in plasmatic levels of corticosterone (CORT), memory decline, elevation of interleukins (IL) levels, and astrocytes activation (Hayakawa et al, 2007;Lynch, 2010;Murray and Lynch, 1998). Cytokines, like the two immune mediators IL-1β and IL-6, are secreted by activated microglia and are known to trigger astrocytes activation (Woiciechowsky et al, 2004;Zhang et al, 2010).…”

Evidence for a role for the group I metabotropic glutamate receptor in the inhibitory effect of tumor necrosis factor-α on long-term potentiation

“…The signaling mechanism underlying the ability of TNF-α to cause the cognitive dysfunction associated with many of these conditions has been probed, but to date no clear mechanistic understanding has been reached. TNF-α and IL-1β at pathophysiological levels have been shown by many authors to inhibit long-term potentiation (LTP) in the CA1 and the dentate gyrus regions of the rat hippocampus (Cunningham et al, 1996;Murray and Lynch, 1998;Tancredi et al, 1992) but not by others (Stellwagen and Malenka, 2006). IL-1β has been shown to depress NMDAreceptor mediated field potentials in the dentate gyrus (Coogan B R A I N R E S E A R C H 1 1 3 6 ( 2 0 0 7 ) 1 3 -1 9 ⁎ Corresponding author.…”