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Effects of rolipram and roflumilast, phosphodiesterase-4 inhibitors, on hypertension-induced defects in memory function in rats.
Eur J Pharmacol. 2015 Jan 05; 746:138-47.EJ

Abstract

Hypertension (HT) is a prevailing risk factor for cognitive impairment, the most common cause of vascular dementia; yet, no possible mechanism underlying the cognitive impairment induced by hypertension has been identified so far. Inhibition of PDE-4 has been shown to increase phosphorylation of cAMP-response element binding protein in the hippocampus and enhance the memory performance. Here, we examined the effects of PDE-4 inhibitors, rolipram and roflumilast, on the impairment of learning and memory observed in hypertensive rats. We used 2k-1c hypertensive model to induce learning and memory defects. In addition, mRNA expression of PDE-4 sub-types A-D was also assessed in the hippocampus tissue. Systolic blood pressure (SBP) was measured by tail-cuff method was significantly increased in 2k-1c rats when compared to sham operated rats; this effect was reversed by clonidine, whereas, PDE-4 inhibitors did not. PDE-4 inhibitors significantly reversed time induced memory deficit in novel object recognition task (NORT). Further, the retention latency on the second day in the elevated plus maze model was significantly shortened after repeated administration of rolipram and roflumilast. Plasma and brain concentrations of rolipram, roflumilast and roflumilast N-oxide were also measured after the NORT and showed linear increase in plasma and brain concentrations. The PDE4B and PDE4D gene expression was significantly enhanced in hypertensive rats compared with sham operated however PDE4A and PDE4C remained unaltered. Repeated treatment with PDE-4 inhibitors caused down regulation of PDE4B and PDE4D in hypertensive rats. These results suggest that inhibition of PDE-4 ameliorates HT-induced impairment of learning and memory functions.

Authors+Show Affiliations

Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai 600116, Tamil Nadu, India.Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai 600116, Tamil Nadu, India.Central Leather Research Institute, Council of Scientific and Industrial Research, Chennai 600020, Tamil Nadu, India.AstraZeneca India Pvt. Ltd., Off Bellary Road, Hebbal, Bangalore 560024, India.Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai 600116, Tamil Nadu, India.Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai 600116, Tamil Nadu, India. Electronic address: ceftpublications@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25446433

Citation

Jabaris, Sobhana George Sugin Lal, et al. "Effects of Rolipram and Roflumilast, Phosphodiesterase-4 Inhibitors, On Hypertension-induced Defects in Memory Function in Rats." European Journal of Pharmacology, vol. 746, 2015, pp. 138-47.
Jabaris SG, Sumathy H, Kumar RS, et al. Effects of rolipram and roflumilast, phosphodiesterase-4 inhibitors, on hypertension-induced defects in memory function in rats. Eur J Pharmacol. 2015;746:138-47.
Jabaris, S. G., Sumathy, H., Kumar, R. S., Narayanan, S., Thanikachalam, S., & Babu, C. S. (2015). Effects of rolipram and roflumilast, phosphodiesterase-4 inhibitors, on hypertension-induced defects in memory function in rats. European Journal of Pharmacology, 746, 138-47. https://doi.org/10.1016/j.ejphar.2014.10.039
Jabaris SG, et al. Effects of Rolipram and Roflumilast, Phosphodiesterase-4 Inhibitors, On Hypertension-induced Defects in Memory Function in Rats. Eur J Pharmacol. 2015 Jan 5;746:138-47. PubMed PMID: 25446433.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of rolipram and roflumilast, phosphodiesterase-4 inhibitors, on hypertension-induced defects in memory function in rats. AU - Jabaris,Sobhana George Sugin Lal, AU - Sumathy,Haridass, AU - Kumar,Ramadass Satiesh, AU - Narayanan,Shridhar, AU - Thanikachalam,Sadagopan, AU - Babu,Chidambaram Saravana, Y1 - 2014/11/06/ PY - 2014/06/22/received PY - 2014/10/16/revised PY - 2014/10/18/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/9/2/medline KW - Cognition KW - Hypertension KW - Roflumilast KW - Roflumilast N-oxide KW - Rolipram SP - 138 EP - 47 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 746 N2 - Hypertension (HT) is a prevailing risk factor for cognitive impairment, the most common cause of vascular dementia; yet, no possible mechanism underlying the cognitive impairment induced by hypertension has been identified so far. Inhibition of PDE-4 has been shown to increase phosphorylation of cAMP-response element binding protein in the hippocampus and enhance the memory performance. Here, we examined the effects of PDE-4 inhibitors, rolipram and roflumilast, on the impairment of learning and memory observed in hypertensive rats. We used 2k-1c hypertensive model to induce learning and memory defects. In addition, mRNA expression of PDE-4 sub-types A-D was also assessed in the hippocampus tissue. Systolic blood pressure (SBP) was measured by tail-cuff method was significantly increased in 2k-1c rats when compared to sham operated rats; this effect was reversed by clonidine, whereas, PDE-4 inhibitors did not. PDE-4 inhibitors significantly reversed time induced memory deficit in novel object recognition task (NORT). Further, the retention latency on the second day in the elevated plus maze model was significantly shortened after repeated administration of rolipram and roflumilast. Plasma and brain concentrations of rolipram, roflumilast and roflumilast N-oxide were also measured after the NORT and showed linear increase in plasma and brain concentrations. The PDE4B and PDE4D gene expression was significantly enhanced in hypertensive rats compared with sham operated however PDE4A and PDE4C remained unaltered. Repeated treatment with PDE-4 inhibitors caused down regulation of PDE4B and PDE4D in hypertensive rats. These results suggest that inhibition of PDE-4 ameliorates HT-induced impairment of learning and memory functions. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/25446433/Effects_of_rolipram_and_roflumilast_phosphodiesterase_4_inhibitors_on_hypertension_induced_defects_in_memory_function_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(14)00746-8 DB - PRIME DP - Unbound Medicine ER -