scholarly journals Effects of Dexmedetomidine on Rats with Functional Chronic Visceral Pain Based on Protein Expressions in the Extracellular Signal-Regulated Kinase 1/Cyclic Adenosine Monophosphate Response Element-Binding Protein Signaling Pathway

2021 ◽  
Vol 83 (3) ◽  
Author(s):  
J. Li ◽  
Huizhong Tang ◽  
Li Ma
Keyword(s):  
Signaling Pathway ◽  
Visceral Pain ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Protein Signaling ◽  
Response Element ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Protein Expressions ◽  
Element Binding Protein

scholarly journals Cyclic AMP response element-binding protein is required in excitatory neurons in the forebrain to sustain wakefulness

SLEEP ◽  
2020 ◽  
Author(s):  
Mathieu E Wimmer ◽  
Rosa Cui ◽  
Jennifer M Blackwell ◽  
Ted Abel
Keyword(s):  
Cyclic Amp ◽  
Intracellular Signaling ◽  
Target Genes ◽  
Binding Protein ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Response Element ◽  
Creb Phosphorylation ◽  
Element Binding Protein ◽  
And Control

Abstract The molecular and intracellular signaling processes that control sleep and wake states remain largely unknown. A consistent observation is that the cyclic adenosine monophosphate (AMP) response element-binding protein (CREB), an activity-dependent transcription factor, is differentially activated during sleep and wakefulness. CREB is phosphorylated by the cyclic AMP/protein kinase A (cAMP/PKA) signaling pathway as well as other kinases, and phosphorylated CREB promotes the transcription of target genes. Genetic studies in flies and mice suggest that CREB signaling influences sleep/wake states by promoting and stabilizing wakefulness. However, it remains unclear where in the brain CREB is required to drive wakefulness. In rats, CREB phosphorylation increases in the cerebral cortex during wakefulness and decreases during sleep, but it is not known if this change is functionally relevant to the maintenance of wakefulness. Here, we used the Cre/lox system to conditionally delete CREB in the forebrain (FB) and in the locus coeruleus (LC), two regions known to be important for the production of arousal and wakefulness. We used polysomnography to measure sleep/wake levels and sleep architecture in conditional CREB mutant mice and control littermates. We found that FB-specific deletion of CREB decreased wakefulness and increased non-rapid eye movement sleep. Mice lacking CREB in the FB were unable to sustain normal periods of wakefulness. On the other hand, deletion of CREB from LC neurons did not change sleep/wake levels or sleep/wake architecture. Taken together, these results suggest that CREB is required in neurons within the FB but not in the LC to promote and stabilize wakefulness.

Bumetanide, an Inhibitor of Cation-chloride Cotransporter Isoform 1, Inhibits γ-Aminobutyric Acidergic Excitatory Actions and Enhances Sedative Actions of Midazolam in Neonatal Rats

2013 ◽  
Vol 119 (5) ◽  
pp. 1096-1108 ◽  
Author(s):  
Yukihide Koyama ◽  
Tomio Andoh ◽  
Yoshinori Kamiya ◽  
Satoshi Morita ◽  
Tomoyuki Miyazaki ◽  
...  
Keyword(s):  
Binding Protein ◽  
Hippocampal Slices ◽  
Intraperitoneal Administration ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Aminobutyric Acid ◽  
Neonatal Rats ◽  
Response Element ◽  
Sedative Effects ◽  
Element Binding Protein

Abstract Background: It has been shown that γ-aminobutyric acid exerts excitatory actions on the immature brain due to the increased expression of Na+–K+–2Cl− cotransporter isoform 1. The authors sought to clarify whether midazolam, a γ-aminobutyric acid–mimetic hypnotic agent, causes neuronal excitation that can be blocked by bumetanide, a selective inhibitor of Na+–K+–2Cl− cotransporter isoform 1. Furthermore, the authors examined whether bumetanide potentiates the sedative effects of midazolam in neonatal rats. Methods: The authors measured the effects of midazolam with or without bumetanide on the cytosolic Ca2+ concentration ([Ca]2+i) in hippocampal slices (n = 3 in each condition) from rats at postnatal days 4, 7, and 28 (P4, P7, and P28) using fura-2 microfluorometry. Neuronal activity in the hippocampus and thalamus after intraperitoneal administration of midazolam with or without bumetanide was estimated by immunostaining of phosphorylated cyclic adenosine monophosphate–response element–binding protein (n = 12 in each condition). Furthermore, the authors assessed effects of bumetanide on the sedative effect of midazolam by measuring righting reflex latency (n = 6 in each condition). Results: Midazolam significantly increased [Ca]2+i in the CA3 area at P4 and P7 but not at P28. Bumetanide inhibited midazolam-induced increase in [Ca]2+i. Midazolam significantly up-regulated phosphorylated cyclic adenosine monophosphate–response element–binding protein expression in a bumetanide-sensitive manner in the hippocampus at P7 but not P28. Bumetanide enhanced the sedative effects of midazolam in P4 and P7 but not P28 rats. Conclusion: These results suggest that γ-aminobutyric acid A receptor–mediated excitation plays an important role in attenuated sedative effects of midazolam in immature rats.

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