Candesartan improves memory decline in mice: involvement of AT1 receptors in memory deficit induced by intracerebral streptozotocin.
The Renin-angiotensin system, besides blood pressure regulation, affects learning and memory as evidenced by improvement of cognition in hypertensive patients being treated with AT1 receptor blockers like candesartan. The present study examined the influence of candesartan on memory impairment induced by intracerebral streptozotocin (IC STZ 0.5 mg/kg) in mice. Candesartan (0.05 mg/kg and 0.1 mg/kg, i.p.) was given for 14 days following IC STZ administration. The dose of 0.1 mg/kg significantly improved latency period in passive avoidance test. Further, treatment with 0.1 mg/kg candesartan for 14 days significantly improved spatial memory in mice in water maze test also. In another group, after memory impairment in mice following IC STZ administration, memory improving effect of a 7 days treatment with 0.1 mg/kg candesartan lasted only for 3 subsequent days in water maze task. IC STZ increased oxidative stress but pretreatment with 0.1 mg/kg candesartan decreased oxidative stress as indicated by a decrease in MDA and increase in GSH. Further, candesartan decreased free radicals as evidenced by flow cytometry. IC STZ affected cholinergic system also by increasing acetylcholine esterase activity that was restored by pretreatment with 0.1 mg/kg candesartan. Locomotor activity and serum glucose level remained unaffected by candesartan treatment. These results suggest that AT1 receptors play a facilitatory role in STZ induced memory deficit and corroborate number of human studies that AT1 receptor blockers can be used therapeutically against cognitive decline in hypertensive patients.
Tota
Santoshkumar
S
Division of Pharmacology, Central Drug Research Institute, P.O. Box 173, Lucknow, U.P. 226001, India.
Kamat
Pradeep K
PK
Awasthi
Himani
H
Singh
Nilendra
N
Raghubir
Ram
R
Nath
Chandishwar
C
Hanif
Kashif
K
D000110:Acetylcholinesterase / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001786:Blood Glucose; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology*; D013311:Streptozocin / Q000008:administration & dosage / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D001786:Blood Glucose; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D008315:Malondialdehyde; D013311:Streptozocin; D000110:Acetylcholinesterase; C081643:candesartan