Genetic Deletion of Prostacyclin IP Receptor Exacerbates Transient Global Cerebral Ischemia in Aging Mice

Overview

Journal Brain Sci

Publisher MDPI

Date 2014 Mar 18

PMID 24634780

Citations 10

Authors

Hania Shakil

Sofiyan Saleem

Affiliations

Soon will be listed here.

Abstract

Transient global cerebral ischemia causes delayed neuronal death in the hippocampal CA1 region. It also induces an up regulation of cyclooxygenase 2 (COX-2), which generates several metabolites of arachidonic acid, known as prostanoids, including Prostaglandin I2 (PGI2). The present study investigated whether the PGI2 IP receptor plays an important role in brain injury after global cerebral ischemia in aged mice. Adult young (2-3 months) and aged (12-15 months) male C57Bl/6 wild-type (WT) or IP receptor knockout (IP KO) mice underwent a 12 min bilateral common carotid artery occlusion (BCCAO) or a sham surgery. Behavior tests (neurologic deficit and T-maze) were performed 3 and 7 days after BCCAO. After seven days of reperfusion, the numbers of cells positive for markers of neurons, astrocytes, microglia, myeloperoxidase (MPO) and phosphorylated CREB (p-CREB) were evaluated immunohistochemically. Interestingly, in young and aged IP KO ischemic mice, there was a significant increase (p < 0.01) in cognitive deficit, hippocampal CA1 pyramidal neuron death, microglia and MPO activation, while p-CREB was reduced as compared to their corresponding WT controls. These data suggest that following ischemia, IP receptor deletion contributes to memory and cognitive deficits regulated by the CREB pathway and that treatment with IP receptor agonists could be a useful target to prevent harmful consequences.

Citing Articles

p38 MAPK Endogenous Inhibition Improves Neurological Deficits in Global Cerebral Ischemia/Reperfusion Mice.

Hou K, Xiao Z, Dai H Neural Plast. 2022; 2022:3300327.

PMID: 35811833 PMC: 9259354. DOI: 10.1155/2022/3300327.

Correction: Shakil, H.; Saleem, S. Genetic Deletion of Prostacyclin IP Receptor Exacerbates Transient Global Cerebral Ischemia in Aging Mice. 2013, , 1095-1108.

Shakil H, Saleem S Brain Sci. 2021; 11(5).

PMID: 34068448 PMC: 8152957. DOI: 10.3390/brainsci11050624.

Small molecules targeting cyclooxygenase/prostanoid cascade in experimental brain ischemia: Do they translate?.

Jiang J, Yu Y Med Res Rev. 2020; 41(2):828-857.

PMID: 33094540 PMC: 7906918. DOI: 10.1002/med.21744.

Creating a mouse model resistant to induced ischemic stroke and cardiovascular damage.

Ling Q, Mohite A, Murdoch E, Akasaka H, Li Q, So S Sci Rep. 2018; 8(1):1653.

PMID: 29374184 PMC: 5786049. DOI: 10.1038/s41598-018-19661-y.

Expression and Processing of Amyloid Precursor Protein in Vascular Endothelium.

Duscio L, He T, Katusic Z Physiology (Bethesda). 2016; 32(1):20-32.

PMID: 27927802 PMC: 5338593. DOI: 10.1152/physiol.00021.2016.

References

Mizuno M, Yamada K, Maekawa N, Saito K, Seishima M, Nabeshima T . CREB phosphorylation as a molecular marker of memory processing in the hippocampus for spatial learning. Behav Brain Res. 2002; 133(2):135-41. DOI: 10.1016/s0166-4328(01)00470-3. View

Kim D, Jeon S, Son K, Jung J, Lee S, Yoon B . Effect of the flavonoid, oroxylin A, on transient cerebral hypoperfusion-induced memory impairment in mice. Pharmacol Biochem Behav. 2006; 85(3):658-68. DOI: 10.1016/j.pbb.2006.10.025. View

Neumar R . Molecular mechanisms of ischemic neuronal injury. Ann Emerg Med. 2000; 36(5):483-506. DOI: 10.1067/mem.2000.110995. View

Kreutzberg G . Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996; 19(8):312-8. DOI: 10.1016/0166-2236(96)10049-7. View

Neumann J, Cohan C, Dave K, Wright C, Perez-Pinzon M . Global cerebral ischemia: synaptic and cognitive dysfunction. Curr Drug Targets. 2012; 14(1):20-35. PMC: 5800514. DOI: 10.2174/138945013804806514. View

Rodriguez L, Egan K, FitzGerald G . Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction?. PLoS Med. 2007; 4(5):e157. PMC: 1872041. DOI: 10.1371/journal.pmed.0040157. View

McGettigan P, Henry D . Current problems with non-specific COX inhibitors. Curr Pharm Des. 2000; 6(17):1693-724. DOI: 10.2174/1381612003398690. View

Zhou Y, Won J, Karlsson M, Zhou M, Rogerson T, Balaji J . CREB regulates excitability and the allocation of memory to subsets of neurons in the amygdala. Nat Neurosci. 2009; 12(11):1438-43. PMC: 2783698. DOI: 10.1038/nn.2405. View

Saleem S, Shah Z, Maruyama T, Narumiya S, Dore S . Neuroprotective properties of prostaglandin I2 IP receptor in focal cerebral ischemia. Neuroscience. 2010; 170(1):317-23. PMC: 6010185. DOI: 10.1016/j.neuroscience.2010.06.060. View

10.

Gonzalez G, Montminy M . Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell. 1989; 59(4):675-80. DOI: 10.1016/0092-8674(89)90013-5. View

11.

Chen Y, Huang X, Zhang Y, Rockenstein E, Bu G, Golde T . Alzheimer's β-secretase (BACE1) regulates the cAMP/PKA/CREB pathway independently of β-amyloid. J Neurosci. 2012; 32(33):11390-5. PMC: 3446780. DOI: 10.1523/JNEUROSCI.0757-12.2012. View

12.

Yiu A, Rashid A, Josselyn S . Increasing CREB function in the CA1 region of dorsal hippocampus rescues the spatial memory deficits in a mouse model of Alzheimer's disease. Neuropsychopharmacology. 2011; 36(11):2169-86. PMC: 3176558. DOI: 10.1038/npp.2011.107. View

13.

Krajewska M, You Z, Rong J, Kress C, Huang X, Yang J . Neuronal deletion of caspase 8 protects against brain injury in mouse models of controlled cortical impact and kainic acid-induced excitotoxicity. PLoS One. 2011; 6(9):e24341. PMC: 3174961. DOI: 10.1371/journal.pone.0024341. View

14.

Chan E, Dusting G, Guo N, Peshavariya H, Taylor C, Dilley R . Prostacyclin receptor suppresses cardiac fibrosis: role of CREB phosphorylation. J Mol Cell Cardiol. 2010; 49(2):176-85. DOI: 10.1016/j.yjmcc.2010.04.006. View

15.

Gryglewski R, Nowak S, KUSMIDERSKI J, Dembinska-Kiec A, Bieron K, Basista M . Treatment of ischaemic stroke with prostacyclin. Stroke. 1983; 14(2):197-202. DOI: 10.1161/01.str.14.2.197. View

16.

Hoth K, Poppas A, Moser D, Paul R, Cohen R . Cardiac dysfunction and cognition in older adults with heart failure. Cogn Behav Neurol. 2008; 21(2):65-72. DOI: 10.1097/WNN.0b013e3181799dc8. View

17.

Yamamoto Y, Shioda N, Han F, Moriguchi S, Nakajima A, Yokosuka A . Nobiletin improves brain ischemia-induced learning and memory deficits through stimulation of CaMKII and CREB phosphorylation. Brain Res. 2009; 1295:218-29. DOI: 10.1016/j.brainres.2009.07.081. View

18.

Masuda Y, Yasuba M, Zushi K, Ochi Y, Kadokawa T, Okegawa T . Effect of OP-2507, a stable prostacyclin analogue on cerebral ischemia induced by unilateral ligation of common carotid artery in gerbils. Arch Int Pharmacodyn Ther. 1988; 294:125-36. View

19.

Sato Y, Kitani K, Kanai S, Nokubo M, Ohta M . Differences in tolerance to hypoxia/anoxia in mice of different ages. Res Commun Chem Pathol Pharmacol. 1991; 73(2):209-20. View

20.

Moncada D, Viola H . Phosphorylation state of CREB in the rat hippocampus: a molecular switch between spatial novelty and spatial familiarity?. Neurobiol Learn Mem. 2006; 86(1):9-18. DOI: 10.1016/j.nlm.2005.12.002. View