TY - JOUR
T1 - Role of central angiotensin receptors in scopolamine-induced impairment in memory, cerebral blood flow, and cholinergic function
AU - Tota, Santosh Kumar
AU - Hanif, Kashif
AU - Kamat, Pradeep Kumar
AU - Najmi, Abul Kalam
AU - Nath, Chandishwar
N1 - Funding Information:
Acknowledgments Financial support to Santoshkumar Tota from Council of Scientific and Industrial Research (CSIR) New Delhi, India is gratefully acknowledged.
PY - 2012/7
Y1 - 2012/7
N2 - Rational Inhibition of renin-angiotensin system (RAS) improves cognitive functions in hypertensive patients. However, role of AT1 and AT2 receptors in memory impairment due to cholinergic hypofunction is unexplored. Objective This study investigated the role of AT1 and AT2 receptors in cerebral blood flow (CBF), cholinergic neurotransmission, and cerebral energy metabolism in scopolamineinduced amnesic mice. Methods Scopolamine was given to male Swiss albino mice to induce memory impairment tested in passive avoidance and Morris water maze tests after a weeklong administration of blocker of AT1 receptor, candesartan, and AT2 receptor, PD123, 319. CBF was measured by laser Doppler flowmetry. Biochemical and molecular studies were done in cortex and hippocampus of mice brain. Results Scopolamine caused memory impairment, reduced CBF, acetylcholine (ACh) level, elevated acetylcholinesterase (AChE) activity, and malondialdehyde (MDA). Administration of vehicle had no significant effect on any parameter in comparison to control. Candesartan prevented scopolamineinduced amnesia, restored CBF and ACh level, and decreased AChE activity and MDA level. In contrast, PD123, 319 was not effective. However, the effect of AT1 receptor blocker on memory, CBF, ACh level, and oxidative stress was blunted by concomitant blockade of AT2 receptor. Angiotensin-converting enzyme (ACE) activity, ATP level, and mRNA expression of AT1, AT2, and ACE remained unaltered. Conclusion The study suggests that activation of AT1 receptors appears to be involved in the scopolamine-induced amnesia and that AT2 receptors contribute to the beneficial effects of candesartan. Theses finding corroborated the number of clinical studies that RAS inhibition in hypertensive patients could be neuroprotective.
AB - Rational Inhibition of renin-angiotensin system (RAS) improves cognitive functions in hypertensive patients. However, role of AT1 and AT2 receptors in memory impairment due to cholinergic hypofunction is unexplored. Objective This study investigated the role of AT1 and AT2 receptors in cerebral blood flow (CBF), cholinergic neurotransmission, and cerebral energy metabolism in scopolamineinduced amnesic mice. Methods Scopolamine was given to male Swiss albino mice to induce memory impairment tested in passive avoidance and Morris water maze tests after a weeklong administration of blocker of AT1 receptor, candesartan, and AT2 receptor, PD123, 319. CBF was measured by laser Doppler flowmetry. Biochemical and molecular studies were done in cortex and hippocampus of mice brain. Results Scopolamine caused memory impairment, reduced CBF, acetylcholine (ACh) level, elevated acetylcholinesterase (AChE) activity, and malondialdehyde (MDA). Administration of vehicle had no significant effect on any parameter in comparison to control. Candesartan prevented scopolamineinduced amnesia, restored CBF and ACh level, and decreased AChE activity and MDA level. In contrast, PD123, 319 was not effective. However, the effect of AT1 receptor blocker on memory, CBF, ACh level, and oxidative stress was blunted by concomitant blockade of AT2 receptor. Angiotensin-converting enzyme (ACE) activity, ATP level, and mRNA expression of AT1, AT2, and ACE remained unaltered. Conclusion The study suggests that activation of AT1 receptors appears to be involved in the scopolamine-induced amnesia and that AT2 receptors contribute to the beneficial effects of candesartan. Theses finding corroborated the number of clinical studies that RAS inhibition in hypertensive patients could be neuroprotective.
KW - Angiotensin receptors
KW - Candesartan
KW - Memory
KW - PD123,319
KW - Scopolamine
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U2 - 10.1007/s00213-012-2639-7
DO - 10.1007/s00213-012-2639-7
M3 - Article
C2 - 22362194
AN - SCOPUS:84864474059
SN - 0033-3158
VL - 222
SP - 185
EP - 202
JO - Psychopharmacology
JF - Psychopharmacology
IS - 2
ER -