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Hypertension exacerbates predisposition to neurodegeneration and memory impairment in the presence of a neuroinflammatory stimulus: Protection by angiotensin converting enzyme inhibition.
Pharmacol Biochem Behav. 2015 Jun; 133:132-45.PB

Abstract

Hypertension is a risk factor for cognitive impairment. Furthermore, neuroinflammation and neurodegeneration are intricately associated with memory impairment. Therefore, the present study aimed to explore the involvement of hypertension and angiotensin system in neurodegeneration and memory dysfunction in the presence of neuroinflammatory stimulus. Memory impairment was induced by chronic neuroinflammation that was developed by repeated intracerebroventricular (ICV) injections of lipopolysaccharide (LPS) on the 1st, 4th, 7th, and 10th day. Memory functions were evaluated by the Morris water maze (MWM) test on days 13-15, followed by biochemical and molecular studies in the cortex and hippocampus regions of rat brain. LPS at the dose of 25μg ICV caused memory impairment in spontaneously hypertensive rats (SHRs) but not in normotensive Wistar rats (NWRs). Memory deficit was obtained with 50μg of LPS (ICV) in NWRs. Control SHRs already exhibited increased angiotensin converting enzyme (ACE) activity and expression, neuroinflammation (increased TNF-α, GFAP, COX-2 and NF-kB), oxidative stress (increased iNOS, ROS and nitrite levels), TLR-4 expression and TUNEL positive cells as compared to control NWRs. Further, LPS (25μg ICV) exaggerated inflammatory response, oxidative stress and apoptosis in SHRs but similar effects were witnessed at 50μg of LPS (ICV) in NWRs. Oral administration of perindopril (ACE inhibitor), at non-antihypertensive dose (0.1mg/kg), for 15days attenuated LPS induced deleterious changes in both NWRs and SHRs. Our data suggest that susceptibility of the brain for neurodegeneration and memory impairment induced by neuroinflammation is enhanced in hypertension, and that can be protected by ACE inhibition.

Authors+Show Affiliations

Divisions of Pharmacology and Toxicology, CSIR-Central Drug Research Institute, Lucknow 226031, India.Divisions of Pharmacology and Toxicology, CSIR-Central Drug Research Institute, Lucknow 226031, India.Divisions of Pharmacology and Toxicology, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), India.Divisions of Pharmacology and Toxicology, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), India.Divisions of Pharmacology and Toxicology, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), India.Divisions of Pharmacology and Toxicology, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), India. Electronic address: rakeshshukla_cdri@rediffmail.com.

Pub Type(s)

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

Language

eng

PubMed ID

25869103

Citation

Goel, Ruby, et al. "Hypertension Exacerbates Predisposition to Neurodegeneration and Memory Impairment in the Presence of a Neuroinflammatory Stimulus: Protection By Angiotensin Converting Enzyme Inhibition." Pharmacology, Biochemistry, and Behavior, vol. 133, 2015, pp. 132-45.
Goel R, Bhat SA, Rajasekar N, et al. Hypertension exacerbates predisposition to neurodegeneration and memory impairment in the presence of a neuroinflammatory stimulus: Protection by angiotensin converting enzyme inhibition. Pharmacol Biochem Behav. 2015;133:132-45.
Goel, R., Bhat, S. A., Rajasekar, N., Hanif, K., Nath, C., & Shukla, R. (2015). Hypertension exacerbates predisposition to neurodegeneration and memory impairment in the presence of a neuroinflammatory stimulus: Protection by angiotensin converting enzyme inhibition. Pharmacology, Biochemistry, and Behavior, 133, 132-45. https://doi.org/10.1016/j.pbb.2015.04.002
Goel R, et al. Hypertension Exacerbates Predisposition to Neurodegeneration and Memory Impairment in the Presence of a Neuroinflammatory Stimulus: Protection By Angiotensin Converting Enzyme Inhibition. Pharmacol Biochem Behav. 2015;133:132-45. PubMed PMID: 25869103.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypertension exacerbates predisposition to neurodegeneration and memory impairment in the presence of a neuroinflammatory stimulus: Protection by angiotensin converting enzyme inhibition. AU - Goel,Ruby, AU - Bhat,Shahnawaz Ali, AU - Rajasekar,N, AU - Hanif,Kashif, AU - Nath,Chandishwar, AU - Shukla,Rakesh, Y1 - 2015/04/11/ PY - 2014/09/24/received PY - 2015/03/17/revised PY - 2015/04/06/accepted PY - 2015/4/15/entrez PY - 2015/4/15/pubmed PY - 2016/3/5/medline KW - Angiotensin converting enzyme KW - Hypertension KW - Lipopolysaccharide KW - Memory impairment KW - Neuroinflammation KW - Perindopril SP - 132 EP - 45 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 133 N2 - Hypertension is a risk factor for cognitive impairment. Furthermore, neuroinflammation and neurodegeneration are intricately associated with memory impairment. Therefore, the present study aimed to explore the involvement of hypertension and angiotensin system in neurodegeneration and memory dysfunction in the presence of neuroinflammatory stimulus. Memory impairment was induced by chronic neuroinflammation that was developed by repeated intracerebroventricular (ICV) injections of lipopolysaccharide (LPS) on the 1st, 4th, 7th, and 10th day. Memory functions were evaluated by the Morris water maze (MWM) test on days 13-15, followed by biochemical and molecular studies in the cortex and hippocampus regions of rat brain. LPS at the dose of 25μg ICV caused memory impairment in spontaneously hypertensive rats (SHRs) but not in normotensive Wistar rats (NWRs). Memory deficit was obtained with 50μg of LPS (ICV) in NWRs. Control SHRs already exhibited increased angiotensin converting enzyme (ACE) activity and expression, neuroinflammation (increased TNF-α, GFAP, COX-2 and NF-kB), oxidative stress (increased iNOS, ROS and nitrite levels), TLR-4 expression and TUNEL positive cells as compared to control NWRs. Further, LPS (25μg ICV) exaggerated inflammatory response, oxidative stress and apoptosis in SHRs but similar effects were witnessed at 50μg of LPS (ICV) in NWRs. Oral administration of perindopril (ACE inhibitor), at non-antihypertensive dose (0.1mg/kg), for 15days attenuated LPS induced deleterious changes in both NWRs and SHRs. Our data suggest that susceptibility of the brain for neurodegeneration and memory impairment induced by neuroinflammation is enhanced in hypertension, and that can be protected by ACE inhibition. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/25869103/Hypertension_exacerbates_predisposition_to_neurodegeneration_and_memory_impairment_in_the_presence_of_a_neuroinflammatory_stimulus:_Protection_by_angiotensin_converting_enzyme_inhibition_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(15)00119-7 DB - PRIME DP - Unbound Medicine ER -