A cross-sectional comparison of ethanol-related cytokine expression in the hippocampus of young and aged Fischer 344 rats

Abstract

Our work in Sprague Dawley rats has shown rapid alterations in neuroimmune gene expression (RANGE) in the hippocampus and paraventricular nucleus of the hypothalamus (PVN). These manifest as increased Interleukin (IL)-6 and IκBα, and suppressed IL-1β and Tumor necrosis factor alpha (TNFα) during acute ethanol intoxication. The present studies tested these effects across the lifespan (young adulthood at 2–3 months; senescence at 18 and 24 months), as well as across strain (Fischer 344) and sex. The hippocampus revealed age-dependent shifts in cytokine expression [IL-6, IL-1β, Monocyte chemoattractant protein 1], but no changes observed in the PVN at baseline or following ethanol. RANGE in adults was similar across sex and comparable to effects seen in Sprague Dawley rats. Plasma corticosterone levels increased with age, while the blood ethanol concentrations and loss of righting reflex were similar in all groups older than 2 months. These findings indicate that the RANGE effect is largely conserved across strain and is durable across age, even in the face of a shifting neuroimmune profile that emerges during immunosenescence.

Conditioning the neuroimmune response to ethanol using taste and environmental cues in adolescent and adult rats

“…7 Follow-up work replicated this effect and extended it to other brain regions (i.e. amygdala), repeated ethanol exposures, and other rat strains, [8][9][10] suggesting that ethanol-induced IL-6 expression is highly reproducible and much more widespread in the CNS than originally thought.…”

“…We expected that cues associated with ethanol would elicit a conditioned increase in IL-6 and IjBa two neuroimmune genes known to increase during ethanol intoxication. 7,8,10 As an added benefit, this procedure allowed us to examine behavioral conditioning (i.e. avoidance of the taste CS) in tandem with the potential neuroimmune adaptations.…”

“…VT6450, Radnor, PA), and plasma was separated via refrigerated centrifugation and stored at -20 C until time of use. Brains were extracted and stored at -80 C until subsequent tissue dissection using a core-sampling punch technique (as described in Gano et al 10 ) for the extraction of the HPC, AMG, NTS, and PbN.…”

Assessment of Extracellular Cytokines in the Hippocampus of the Awake Behaving Rat Using Large‐Molecule Microdialysis Combined with Multiplex Arrays After Acute and Chronic Ethanol Exposure

“…While these initial foundational studies have focused exclusively on male subjects, it will be necessary to expand our understanding of these effects across sex. While no sex differences have been shown in the neuroimmune gene expression response to acute alcohol challenge as far as IL‐1β, TNF‐α, and IL‐6 in the hippocampus (Gano et al., ; Gano A, Mondello JE, Doremus‐Fitzwater TL, Deak T, manuscript in preparation), there are more notable differences that emerge as EtOH exposure becomes chronic. For instance, it has been shown that sex differences in the neuroimmune responses to chronic EtOH may be particular to the phase of intoxication (specifically emerging in withdrawal) and would therefore be ideally suited to examination using this novel approach (Alfonso‐Loaches et al., ; Hashimoto and Wiren, ; Wilhelm et al., ).…”

“…It has been shown that while acute EtOH challenge results in a robust release of CORT, chronic EtOH engenders a blunted CORT response to future challenges (Spencer and McEwen, ). The hippocampus was selected as the target brain area of interest due both to prior data having shown its sensitivity to the cytokine‐inducing effects of EtOH (Gano et al., ,b), as well as its vulnerability to the effects of adolescent alcohol exposure (Risher et al., ). In the first experiment, a dose–response approach was used to analyze cytokine concentrations following either a saline injection, or an intraperitoneal (i.p.)…”