P2X7 receptors in body temperature, locomotor activity, and brain mRNA and lncRNA responses to sleep deprivation

Abstract

The ionotropic purine type 2X7 receptor (P2X7R) is a nonspecific cation channel implicated in sleep regulation and brain cytokine release. Many endogenous rhythms covary with sleep, including locomotor activity and core body temperature. Furthermore, brain-hypothalamic cytokines and purines play a role in the regulation of these physiological parameters as well as sleep. We hypothesized that these parameters are also affected by the absence of the P2X7 receptor. Herein, we determine spontaneous expression of body temperature and locomotor activity in wild-type (WT) and P2X7R knockout (KO) mice and how they are affected by sleep deprivation (SD). We also compare hypothalamic, hippocampal, and cortical cytokine- and purine-related receptor and enzyme mRNA expressions before and after SD in WT and P2X7RKO mice. Next, in a hypothesis-generating survey of hypothalamic long noncoding (lnc) RNAs, we compare lncRNA expression levels between strains and after SD. During baseline conditions, P2X7RKO mice had attenuated temperature rhythms compared with WT mice, although locomotor activity patterns were similar in both strains. After 6 h of SD, body temperature and locomotion were enhanced to a greater extent in P2X7RKO mice than in WT mice during the initial 2-3 h after SD. Baseline mRNA levels of cortical TNF-α and P2X4R were higher in the KO mice than WT mice. In response to SD, the KO mice failed to increase hypothalamic adenosine deaminase and P2X4R mRNAs. Further, hypothalamic lncRNA expressions varied by strain, and with SD. Current data are consistent with a role for the P2X7R in thermoregulation and lncRNA involvement in purinergic signaling.

Behavioral, affective, and cognitive alterations induced by individual and combined environmental stressors in rats

“…This means that HAB+PSD caused distinct behavioral alterations depending on the type of behavior evaluated. Although some studies have suggested that HAB and PSD have opposite effects on locomotor activity, we found no evidence of their individual or combined effects on operant behavior 13,16,21,22…”

Translational changes induced by acute sleep deprivation uncovered by TRAP-Seq

“…Additionally, long non-coding RNA molecules would also be excluded from the TRAP-Seq data set. The regulation of sleep and sleep deprivation has been previously shown to affect the expression of long non-coding RNAs in vertebrate and invertebrate models [ 72 , 73 ]. Closer analysis of the microarray transcriptome differentially expressed genes from Vecsey and colleagues [ 10 ] found that 22 genes were glial or non-neuronal, and 108 were long non-coding RNAs; thus, accounting for at least part of the lower than predicted numbers of differentially expressed genes we found in the TRAP-Seq data.…”

“…Additionally, long non-coding RNA molecules would also be excluded from the TRAP-Seq data set. The regulation of sleep and sleep deprivation has been previously shown to affect the expression of long non-coding RNAs in vertebrate and invertebrate models [72,73]. Closer analysis of the microarray transcriptome differentially expressed genes Fig.…”

Sleep Deprivation and the Epigenome

“…LncRNAs have also been linked to circadian machinery; deletion of the lncRNA 116HG causes dysregulation of circadian genes Clock , Cry1 and Per2 (Powell et al, 2013 ). Using a mouse lncRNA array, differential expression of several lncRNAs was observed following sleep deprivation, with increased expression of A230107N01Rik being the most significant result (Davis et al, 2016 ). However, of the lncRNAs affected by sleep deprivation, there has currently been no associated function identified.…”