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Central angiotensin converting enzyme facilitates memory impairment in intracerebroventricular streptozotocin treated rats.
Behav Brain Res. 2012 Jan 01; 226(1):317-30.BB

Abstract

Preclinical and clinical studies indicated involvement of renin angiotensin system (RAS) in memory functions. However, exact role of RAS in cognition is still ambiguous. Our aim was to explore how angiotensin converting enzyme (ACE) modulates memory in experimental model of memory impairment. Memory deficit was induced by intracerebroventricular administration of streptozotocin (STZ, 3mg/kg) in rats. Perindopril, an ACE inhibitor, was given for 21 days and memory function was evaluated by Morris water maze test. Cerebral blood flow (CBF) was measured by laser doppler flowmetry. The biochemical and expression studies were done in cortex and hippocampus of rat brain after the completion of behavioral studies. STZ caused impairment in memory along with significant reduction in CBF, ATP level and elevated oxidative and nitrosative stress. The activity and mRNA expression of acetylcholinesterase (AChE) and ACE were also increased in rat brain regions following STZ administration. However, serum ACE activity remained unaffected. Treatment with perindopril dose dependently improved memory by increasing energy metabolism and CBF. Perindopril also decreased oxidative and nitrosative stress, activity and mRNA expression of AChE and ACE in STZ treated rat. Further, ACE inhibition mitigated STZ induced neurodegeneration as observed in histopathological studies. Moreover, perindopril per se improved memory and CBF, decreased oxidative stress with no effect on AChE activity and expression. However, perindopril per se significantly reduced ACE activity but increased mRNA expression of ACE in rat brain. These results suggest that ACE occupies a pivotal role in STZ induced memory deficit thus implicating central RAS in cognition.

Authors+Show Affiliations

Division of Pharmacology, Central Drug Research Institute, Lucknow U.P.India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21864581

Citation

Tota, Santoshkumar, et al. "Central Angiotensin Converting Enzyme Facilitates Memory Impairment in Intracerebroventricular Streptozotocin Treated Rats." Behavioural Brain Research, vol. 226, no. 1, 2012, pp. 317-30.
Tota S, Kamat PK, Saxena G, et al. Central angiotensin converting enzyme facilitates memory impairment in intracerebroventricular streptozotocin treated rats. Behav Brain Res. 2012;226(1):317-30.
Tota, S., Kamat, P. K., Saxena, G., Hanif, K., Najmi, A. K., & Nath, C. (2012). Central angiotensin converting enzyme facilitates memory impairment in intracerebroventricular streptozotocin treated rats. Behavioural Brain Research, 226(1), 317-30. https://doi.org/10.1016/j.bbr.2011.07.047
Tota S, et al. Central Angiotensin Converting Enzyme Facilitates Memory Impairment in Intracerebroventricular Streptozotocin Treated Rats. Behav Brain Res. 2012 Jan 1;226(1):317-30. PubMed PMID: 21864581.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Central angiotensin converting enzyme facilitates memory impairment in intracerebroventricular streptozotocin treated rats. AU - Tota,Santoshkumar, AU - Kamat,Pradeep Kumar, AU - Saxena,Gunjan, AU - Hanif,Kashif, AU - Najmi,Abul Kalam, AU - Nath,Chandishwar, Y1 - 2011/08/16/ PY - 2011/06/19/received PY - 2011/07/18/revised PY - 2011/07/25/accepted PY - 2011/8/26/entrez PY - 2011/8/26/pubmed PY - 2012/2/10/medline SP - 317 EP - 30 JF - Behavioural brain research JO - Behav Brain Res VL - 226 IS - 1 N2 - Preclinical and clinical studies indicated involvement of renin angiotensin system (RAS) in memory functions. However, exact role of RAS in cognition is still ambiguous. Our aim was to explore how angiotensin converting enzyme (ACE) modulates memory in experimental model of memory impairment. Memory deficit was induced by intracerebroventricular administration of streptozotocin (STZ, 3mg/kg) in rats. Perindopril, an ACE inhibitor, was given for 21 days and memory function was evaluated by Morris water maze test. Cerebral blood flow (CBF) was measured by laser doppler flowmetry. The biochemical and expression studies were done in cortex and hippocampus of rat brain after the completion of behavioral studies. STZ caused impairment in memory along with significant reduction in CBF, ATP level and elevated oxidative and nitrosative stress. The activity and mRNA expression of acetylcholinesterase (AChE) and ACE were also increased in rat brain regions following STZ administration. However, serum ACE activity remained unaffected. Treatment with perindopril dose dependently improved memory by increasing energy metabolism and CBF. Perindopril also decreased oxidative and nitrosative stress, activity and mRNA expression of AChE and ACE in STZ treated rat. Further, ACE inhibition mitigated STZ induced neurodegeneration as observed in histopathological studies. Moreover, perindopril per se improved memory and CBF, decreased oxidative stress with no effect on AChE activity and expression. However, perindopril per se significantly reduced ACE activity but increased mRNA expression of ACE in rat brain. These results suggest that ACE occupies a pivotal role in STZ induced memory deficit thus implicating central RAS in cognition. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/21864581/Central_angiotensin_converting_enzyme_facilitates_memory_impairment_in_intracerebroventricular_streptozotocin_treated_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(11)00577-8 DB - PRIME DP - Unbound Medicine ER -