A possible mechanism for improvement by a cognition‐enhancer nefiracetam of spatial memory function and cAMP‐mediated signal transduction system in sustained cerebral ischaemia in rats

Abstract

1 Accumulated evidence indicates that the adenylyl cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-responsive element binding protein (CREB) signal transduction system may be linked to learning and memory function.2 The e ects of ne®racetam, which has been developed as a cognition enhancer, on spatial memory function and the AC/cAMP/PKA/CREB signal transduction system in rats with sustained cerebral ischaemia were examined. 3 Microsphere embolism (ME)-induced sustained cerebral ischaemia was produced by injection of 700 microspheres (48 mm in diameter) into the right hemisphere of rats. Daily oral administration of ne®racetam (10 mg kg 71 day 71 ) was started from 15 h after the operation. 4 The delayed treatment with ne®racetam attenuated the ME-induced prolongation of the escape latency in the water maze task that was examined on day 7 to 9 after ME, but it did not reduce the infarct size. 5 ME decreased Ca 2+ /calmodulin (CaM)-stimulated AC (AC-I) activity, cAMP content, cytosolic PKA Cb level, nuclear PKA Ca and Cb levels, and reduced the phosphorylation and DNA-binding activity of CREB in the nucleus in the right parietal cortex and hippocampus on day 3 after ME. The ME-induced changes in these variables did not occur by the delayed treatment with ne®racetam. 6 These results suggest that ne®racetam preserved cognitive function, or prevented cognitive dysfunction, after sustained cerebral ischaemia and that the e ect is, in part, attributable to the prevention of the ischaemia-induced impairment of the AC/cAMP/PKA/CREB signal transduction pathway.

WITHDRAWN: Gestational and lactational exposure to atrazine affects behavior and cognitive functions in Sprague-Dawley rats

“…Recent research has implicated the cyclic adenosine monophosphate-protein kinase A-cAMP response elementwww.impactjournals.com/oncotarget/ Oncotarget, Advance Publications 2017 binding protein (cAMP-PKA-CREB) pathway as a key signaling pathway affecting the formation of cognitive function and memory in animals [20][21][22]. This G-coupled receptor signaling pathway involves the activation cAMP which activates PKA and leads to the phosphorylation of CREB.…”

Adenylyl Cyclase/cAMP System Involvement in the Antiangiogenic Effect of Somatostatin in the Retina. Results from Transgenic Mice

“…Alterations of AC isoform expression in response to oxygen deficiency have been observed in different tissues [37,38]. In sst1 or sst2 KO retinas, the combination of hypoxia and sst2 expression level resulted in strain-specific changes.…”

NNK-induced hamster lung adenocarcinomas over-express β2-adrenergic and EGFR signaling pathways

“…In turn, PKA phosporylates the cAMP response element binding protein (CREB) [19][20][21][22]. CREB is a nuclear transcription factor whose role in cardiovascular disease [23][24][25], neurodegenerative disease [26] and stroke [27,28] has been widely studied. The cAMP/PKA/CREB pathway plays an important role in the development and tumorigenesis of endocrine tissues [29] but has not been implicated in the development of other types of cancer.…”