Oral feeding of minocycline attenuates glial activation and reductions of tau and drebrin in response to systemically injected cytokines

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Sickness: From the focus on cytokines, prostaglandins, and complement factors to the perspectives of neurons

Systemic inflammation leads to a variety of physiological (e.g. fever) and behavioral (e.g. anorexia, immobility, social withdrawal, depressed mood, disturbed sleep) responses that are collectively known as sickness. While these phenomena have been studied for the past few decades, the neurobiological mechanisms by which sickness occurs remain unclear. In this review, we first revisit how the body senses and responds to infections and injuries by eliciting systemic inflammation. Next, we focus on how peripheral inflammatory molecules such as cytokines, prostaglandins, and activated complement factors communicate with the brain to trigger neuroinflammation and sickness. Since depression also involves inflammation, we further elaborate on the interrelationship between sickness and depression. Finally, we discuss how immune activation can modulate neurons in the brain, and suggest future perspectives to help unravel how changes in neuronal functions relate to sickness responses

Differential modulation of bacteria-induced sickness and inflammation by double stranded RNA-dependent protein kinase (PKR)

Session: 277. Neuroimmunology: Behavioral Effects: Program no. 277.01; Poster no. EEE22.Sickness refers to a set of adaptive, physiological (e.g. fever) and behavioral (e.g. malaise, anorexia, social withdrawal, and fatigue) changes in response to systemic inflammatory insults, e.g. infection and injury. While these responses collectively serve to facilitate an organism to recover, increasing lines of evidence indicate that sickness, if exacerbated, may precipitate depression and delirium. Hence, it will be beneficial to discover suitable approaches to modulate sickness so as to maximize its benefits and minimize its side effects. As double-stranded RNA-dependent protein kinase (PKR) is key kinase regulating inflammation, the aim of this study is to investigate whether PKR also plays a regulatory role in sickness. PKR+/+ and PKR-/- mice were infected subcutaneously with live Escherichia coli (E. coli.) or vehicle. Sickness was assessed by monitoring fever, food consumption, burrowing, and open field activity for five days. Moreover, the brain and the liver were collected for quantitative polymerase chain reaction (qPCR) of the inflammatory markers interleukin-1β (IL-1β) and cyclooxygenase (COX-2).After being challenged by E. coli., PKR-/- mice developed prolonged fever (2-3 days) as compared to PKR+/+ mice (3-4 days). Moreover, PKR-/- mice showed greater hypophagia during the early phase of sickness (day 1-2), which was followed a more pronounced hyperphagia in the late phase of sickness (day 4-5). While both types of mice displayed similar decreases of burrowing activities, PKR-/- mice exhibited a greater reduction in open field activity than PKR+/+ mice. Furthermore, IL-1ß and COX2 in PKR +/+ and PKR-/- mice were differentially expressed in the brain and the liver following E. coli. challenge.It has been known that PKR participates in up-regulating inflammatory responses in immune cells, and that inflammatory factors such as IL-1β and COX-2 are key players in causing sickness during systemic inflammation. Our data is consistent with the literature that deficiency of PKR could lower the expression of systemic inflammatory markers after immune challenge. These findings shall (1) shed light on the suitability of PKR as a target to modulate sickness, and (2) stimulate us to refine the current concepts relating infection, systemic inflammation, and sickness

The manchester respiratory activities of daily living questionnaire : reliability and validity of the Chinese version with pictorial enhancement

202103 bcrcVersion of RecordPublishe