Tags

Type your tag names separated by a space and hit enter

Phosphodiesterase-4 inhibitors ameliorates cognitive deficits in deoxycorticosterone acetate induced hypertensive rats via cAMP/CREB signaling system.
Brain Res. 2015 Oct 05; 1622:279-91.BR

Abstract

Phosphodiesterase-4 (PDE-4) inhibitors promote memory by blocking the degradation of cAMP. Existing evidence also shows that neuronal survival and plasticity are dependent on the phosphorylation of cAMP-response element-binding protein. In this regard, PDE-4 inhibitors have also been shown to reverse pharmacologically and genetically induced memory impairment in animal models. In the present study, the authors examined the effect of both rolipram and roflumilast (PDE-4 inhibitors) on the impairment of learning and memory observed in hypertensive rats. Deoxycorticosterone acetate (DOCA) salt hypertensive model was used to induce learning and memory deficits. The mRNA expression of different PDE-4 subtypes along with the protein levels of pCREB and BDNF in the hippocampus was quantified. Systolic blood pressure was significantly increased in DOCA salt hypertensive rats when compared to sham operated rats. This effect was reversed by clonidine, an α2 receptor agonist, while PDE-4 inhibitors did not. PDE-4 inhibitors significantly improved the time-induced memory deficits in object recognition task (ORT). In DOCA salt hypertensive rats, the gene expression of PDE-4B and PDE-4D was significantly increased. Furthermore, both pCREB and BDNF showed decreased levels of expression in hypertensive rats in comparison to sham operated rats. Repeated administration of PDE-4 inhibitors significantly decreased both PDE-4B and PDE-4D with an increase in the expression of pCREB and BDNF in hypersensitive rats. Also, rolipram, roflumilast and roflumilast N-oxide showed a linear increase in the plasma and brain concentrations after ORT. Our present findings suggested that PDE-4 inhibitors ameliorate hypertension-induced learning impairment via cAMP/CREB signaling that regulates BDNF expression downstream in the rat hippocampus.

Authors+Show Affiliations

Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University (SRU), Chennai 600116, Tamil Nadu, India.Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University (SRU), Chennai 600116, Tamil Nadu, India.Department of Nephrology, Sri Ramachandra University, Chennai 600116, Tamil Nadu, India; Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University (SRU), Chennai 600116, Tamil Nadu, India.Foundation for Neglected Disease Research, Sri Krishnadevaraya Research Centre, Bangalore 562 157, India.Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University (SRU), Chennai 600116, Tamil Nadu, India.Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University (SRU), Chennai 600116, Tamil Nadu, India. Electronic address: ceftpublications@gmail.com.Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University (SRU), Chennai 600116, Tamil Nadu, India.Tufts University School of Medicine, Boston, MA 02111, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26168894

Citation

Jabaris, S Sugin Lal, et al. "Phosphodiesterase-4 Inhibitors Ameliorates Cognitive Deficits in Deoxycorticosterone Acetate Induced Hypertensive Rats Via cAMP/CREB Signaling System." Brain Research, vol. 1622, 2015, pp. 279-91.
Jabaris SS, Sumathy H, Girish R, et al. Phosphodiesterase-4 inhibitors ameliorates cognitive deficits in deoxycorticosterone acetate induced hypertensive rats via cAMP/CREB signaling system. Brain Res. 2015;1622:279-91.
Jabaris, S. S., Sumathy, H., Girish, R., Narayanan, S., Sugumar, M., Saravana Babu, C., Thanikachalam, S., & Thanikachalam, M. (2015). Phosphodiesterase-4 inhibitors ameliorates cognitive deficits in deoxycorticosterone acetate induced hypertensive rats via cAMP/CREB signaling system. Brain Research, 1622, 279-91. https://doi.org/10.1016/j.brainres.2015.07.003
Jabaris SS, et al. Phosphodiesterase-4 Inhibitors Ameliorates Cognitive Deficits in Deoxycorticosterone Acetate Induced Hypertensive Rats Via cAMP/CREB Signaling System. Brain Res. 2015 Oct 5;1622:279-91. PubMed PMID: 26168894.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phosphodiesterase-4 inhibitors ameliorates cognitive deficits in deoxycorticosterone acetate induced hypertensive rats via cAMP/CREB signaling system. AU - Jabaris,S Sugin Lal, AU - Sumathy,Haridass, AU - Girish,Ramesh, AU - Narayanan,Shridhar, AU - Sugumar,Mani, AU - Saravana Babu,Chidambaram, AU - Thanikachalam,Sadagopan, AU - Thanikachalam,Mohan, Y1 - 2015/07/11/ PY - 2015/03/14/received PY - 2015/07/02/revised PY - 2015/07/03/accepted PY - 2015/7/15/entrez PY - 2015/7/15/pubmed PY - 2016/6/2/medline KW - BDNF KW - Cognition KW - Hypertension KW - Roflumilast KW - Rolipram KW - pCREB SP - 279 EP - 91 JF - Brain research JO - Brain Res. VL - 1622 N2 - Phosphodiesterase-4 (PDE-4) inhibitors promote memory by blocking the degradation of cAMP. Existing evidence also shows that neuronal survival and plasticity are dependent on the phosphorylation of cAMP-response element-binding protein. In this regard, PDE-4 inhibitors have also been shown to reverse pharmacologically and genetically induced memory impairment in animal models. In the present study, the authors examined the effect of both rolipram and roflumilast (PDE-4 inhibitors) on the impairment of learning and memory observed in hypertensive rats. Deoxycorticosterone acetate (DOCA) salt hypertensive model was used to induce learning and memory deficits. The mRNA expression of different PDE-4 subtypes along with the protein levels of pCREB and BDNF in the hippocampus was quantified. Systolic blood pressure was significantly increased in DOCA salt hypertensive rats when compared to sham operated rats. This effect was reversed by clonidine, an α2 receptor agonist, while PDE-4 inhibitors did not. PDE-4 inhibitors significantly improved the time-induced memory deficits in object recognition task (ORT). In DOCA salt hypertensive rats, the gene expression of PDE-4B and PDE-4D was significantly increased. Furthermore, both pCREB and BDNF showed decreased levels of expression in hypertensive rats in comparison to sham operated rats. Repeated administration of PDE-4 inhibitors significantly decreased both PDE-4B and PDE-4D with an increase in the expression of pCREB and BDNF in hypersensitive rats. Also, rolipram, roflumilast and roflumilast N-oxide showed a linear increase in the plasma and brain concentrations after ORT. Our present findings suggested that PDE-4 inhibitors ameliorate hypertension-induced learning impairment via cAMP/CREB signaling that regulates BDNF expression downstream in the rat hippocampus. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/26168894/Phosphodiesterase_4_inhibitors_ameliorates_cognitive_deficits_in_deoxycorticosterone_acetate_induced_hypertensive_rats_via_cAMP/CREB_signaling_system_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(15)00513-2 DB - PRIME DP - Unbound Medicine ER -