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The present study aimed to investigate the effect of APAP treatment on the expression of pro-inflammatory cytokines in the astrocytes. The mouse astrocyte cells (C8-D1A) were treated with APAP at the concentration of 100 μM for 24 h, 16 and 28 days. The expressions of pro-inflammatory cytokines and NF-kB were determined using western blot analysis. Furthermore, the expression and localization of phosphorylation of NF-kB were detected by immunohistochemical and immunofluorescent analysis. The ultrastructure of C8-D1A cells was as well monitored. The results revealed that acute APAP treatment (24 h) had no effect on the expression of pro-inflammatory cytokines and pNF-kB. This treatment did not alter the ultrastructure of C8-D1A cells when compared with those in the control cells. However, the results obtained from the study on chronic APAP-treated cells (16 and 28 days) showed the different effect of APAP treatment. The results obtained from western blot analysis showed the increment of pro-inflammatory cytokine (IL-1β and TNF-α) expressions and the activation of NF-kB signaling pathway. Nuclear translocation of pNF-kB and alteration of several cell structures were well observed in the C8-D1A cells with chronic APAP treatment. The results obtained from this study suggest that chronic APAP treatment can induce an upregulation of pro-inflammatory cytokines (IL-1β and TNFα) in astrocytes. This alteration implies the involvement of the activation of NF-kB signaling pathway.

Paracetamol (acetaminophen, APAP) is known as a safe pain reliever; however, its negative effects on the central nervous system have gradually been reported. We examined alterations in learning and memory, and brain-derived neurotrophic factor (BDNF) expression in the frontal cortex and hippocampus at different durations of APAP treatment in rats. Novel object recognition (NOR) and Morris water maze (MWM) paradigms were used to assess learning and memory in rats fed with 200 mg/kg APAP at single-dose, 15-day or 30-day treatments. BDNF expression was evaluated through immunohistochemistry and Western blotting. The single-dose APAP treatment did not alter the NOR performance. However, deficits in the NOR and MWM capacities were detected in the rats with longer durations of APAP treatment. An analysis of BDNF expression revealed no significant change in BDNF expression in the single-dose APAP treatment, while rats given APAP for extended periods as treatment showed a significant decrement in this protein in the frontal cortex and hippocampus. Short-term APAP treatment has no effect on learning and memory, or BDNF expression; however, long-term APAP exposure causes cognitive impairment. The diminishment of the BDNF level in the frontal cortex and hippocampus due to the long period of treatment with APAP may at least in part be involved in altered learning and memory in rats.

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Chronic overeating is a core feature of diet‐induced obesity. There is increasing evidence that in vulnerable individuals, such overeating could become compulsive, resembling an addictive disorder. The transition to compulsive substance use has been linked with changes at glutamatergic synapses in the nucleus accumbens. In this study, we investigated a potential link between such glutamatergic dysregulation and compulsive‐like eating using a rat model of diet‐induced obesity. A conditioned suppression task demonstrated that diet‐induced obese rats display eating despite negative consequences, as their consumption was insensitive to an aversive cue. Moreover, nucleus accumbens expression of GluA1 and xCT proteins was upregulated in diet‐induced obese animals. Lastly, both a computed ‘addiction score’ (based on performance across three criteria) and weight gain were positively correlated with changes in GluA1 and xCT expression in the nucleus accumbens. These data demonstrate that the propensity for diet‐induced obesity is associated with compulsive‐like eating of highly palatable food and is accompanied by ‘addiction‐like’ glutamatergic dysregulation in the nucleus accumbens, thus providing neurobiological evidence of addiction‐like pathology in this model of obesity.

Aging is generally known to be associated with dynamic biological changes, physiological dysfunction, and environmental and psychological decline. Several studies have suggested that aging is associated with increased inflammatory cytokines, causing several diseases. However, the effect of exercise on aging has been less delineated, and the relationships between cytokine activation, aging, and exercise also need further study. Here, we discuss some ideas about the effect of exercise on aging-induced exaggerated cytokine responses and discuss the possible roles of the aging-induced exaggerated cytokine response following exercise. Evidence from these findings suggests that exercise is a beneficially applicable model to use in studies on the mechanisms underlying the age-associated gradated cytokine response, and these results may provide guidelines for health professionals with diverse backgrounds.