The Intracellular Localization of ID2 Expression Has a Predictive Value in Non Small Cell Lung Cancer

ID2 is a member of a subclass of transcription regulators belonging to the general bHLH (basic-helix-loophelix) family of transcription factors. In normal cells, ID2 is responsible for regulating the balance between proliferation and differentiation. More recent studies have demonstrated that ID2 is involved in tumor progression in several cancer types such as prostate or breast

Dialysis delivery of an adenosine A 2A agonist into the pontine reticular formation of C57BL/6J mouse increases pontine acetylcholine release and sleep

In vivo microdialysis in C57BL/6J (B6) mouse was used to test the hypothesis that activating adenosine A 2A receptors in the pontine reticular formation (PRF) increases acetylcholine (ACh) release and rapid eye movement (REM) sleep. Eight concentrations of the adenosine A 2A receptor agonist 2- p- (2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; CGS) were delivered to the PRF and ACh in the PRF was quantified. ACh release was significantly increased by dialysis with 3 μm CGS and significantly decreased by dialysis with 10 and 100 μm CGS. Co-administration of the adenosine A 2A receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385; 30 nm) blocked the CGS-induced increase in ACh release. In a second series of experiments, CGS (3 μm) was delivered by dialysis to the PRF for 2 h while recording sleep and wakefulness. CGS significantly decreased time in wakefulness (−51% in h 1; −54% in h 2), increased time in non-rapid eye movement (NREM) sleep (90% in h 1; 151% in h 2), and increased both time in REM sleep (331% in h 2) and the number of REM sleep episodes (488% in h 2). The enhancement of REM sleep is consistent with the interpretation that adenosine A 2A receptors in the PRF of the B6 mouse contribute to REM sleep regulation, in part, by increasing ACh release in the PRF. A 2A receptor activation may promote NREM sleep via GABAergic inhibition of arousal promoting neurons in the PRF.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66018/1/j.1471-4159.2006.03700.x.pd

Cholinergic reticular mechanisms influence state-dependent ventilatory response to hypercapnia.

Breathing is impaired by the loss of wakefulness that accompanies sleep, certain comatose states, and anesthesia. Although state-dependent decrements in breathing and the ability to respond to hypercapnic stimuli are characteristic of most mammals, the neural mechanisms that cause state-dependent changes in respiratory control remain poorly understood. The present study examined the hypothesis that cholinergic mechanisms in the medial pontine reticular formation (mPRF) can cause state-dependent changes in breathing and in the hypercapnic ventilatory response (HCVR). Six cats were anesthetized with halothane and chronically instrumented for subsequent studies of breathing during wakefulness, non-rapid-eye-movement (NREM) sleep, rapid-eye-movement (REM) sleep, and during the REM sleep-like state caused by mPRF microinjections of carbachol or bethanechol. Minute ventilation was significantly decreased during the carbachol-induced REM sleep-like state (DCarb) compared with wakefulness. The HCVR in NREM, REM, DCarb, and after bethanechol was less than the waking HCVR. These results show for the first time that cholinoceptive regions in the mPRF can cause state-dependent reductions in normocapnic minute ventilation and in the ventilatory response to hypercapnia