PMID- 27375198
OWN - NLM
STAT- MEDLINE
DCOM- 20170817
LR  - 20181202
IS  - 1873-5177 (Electronic)
IS  - 0091-3057 (Linking)
VI  - 148
DP  - 2016 Sep
TI  - Angiotensin II type 1 receptor blockade by telmisartan prevents stress-induced 
      impairment of memory via HPA axis deactivation and up-regulation of brain-derived 
      neurotrophic factor gene expression.
PG  - 108-18
LID - S0091-3057(16)30110-1 [pii]
LID - 10.1016/j.pbb.2016.06.010 [doi]
AB  - Physical and psychological aspects of chronic stress continue to be a persistent 
      clinical problem for which new pharmacological treatment strategies are 
      aggressively sought. By the results of our previous work it has been demonstrated 
      that telmisartan (TLM), an angiotensin type 1 receptor (AT1) blocker (ARB) and 
      partial agonist of peroxisome proliferator-activated receptor gamma (PPARgamma), 
      alleviates stress-induced cognitive decline. Understanding of mechanistic 
      background of this phenomenon is hampered by both dual binding sites of TLM and 
      limited data on the consequences of central AT1 blockade and PPARgamma activation. 
      Therefore, a critical need exists for progress in the characterization of this 
      target for pro-cognitive drug discovery. An unusual ability of novel ARBs to 
      exert various PPARgamma binding activities is commonly being viewed as predominant 
      over angiotensin blockade in terms of neuroprotection. Here we aimed to verify 
      this hypothesis using an animal model of chronic psychological stress (Wistar 
      rats restrained 2.5h daily for 21days) with simultaneous oral administration of 
      TLM (1mg/kg), GW9662 - PPARgamma receptor antagonist (0.5mg/kg), or both in 
      combination, followed by a battery of behavioral tests (open field, elevated plus 
      maze, inhibitory avoidance - IA, object recognition - OR), quantitative 
      determination of serum corticosterone (CORT) and evaluation of brain-derived 
      neurotrophic factor (BDNF) gene expression in the medial prefrontal cortex (mPFC) 
      and hippocampus (HIP). Stressed animals displayed decreased recall of the IA 
      behavior (p<0.001), decreased OR (p<0.001), substantial CORT increase (p<0.001) 
      and significantly downregulated expression of BDNF in the mPFC (p<0.001), which 
      were attenuated in rats receiving TLM and TLM+GW9662. These data indicate that 
      procognitive effect of ARBs in stressed subjects do not result from PPAR-gamma 
      activation, but AT1 blockade and subsequent hypothalamus-pituitary-adrenal axis 
      deactivation associated with changes in primarily cortical gene expression. This 
      study confirms the dual activities of TLM that controls hypertension and 
      cognition through AT1 blockade.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Wincewicz, D
AU  - Wincewicz D
AD  - Department of Clinical Pharmacology, Medical University of Bialystok, Waszyngtona 
      15a, 15274 Bialystok, Poland; Department of Psychiatry, Medical University of 
      Bialystok, Poland. Electronic address: d.wincewicz@gmail.com.
FAU - Juchniewicz, A
AU  - Juchniewicz A
AD  - Department of Clinical Molecular Biology, Medical University of Bialystok, 
      Poland.
FAU - Waszkiewicz, N
AU  - Waszkiewicz N
AD  - Department of Psychiatry, Medical University of Bialystok, Poland.
FAU - Braszko, J J
AU  - Braszko JJ
AD  - Department of Clinical Pharmacology, Medical University of Bialystok, Waszyngtona 
      15a, 15274 Bialystok, Poland.
LA  - eng
PT  - Journal Article
DEP - 20160701
PL  - United States
TA  - Pharmacol Biochem Behav
JT  - Pharmacology, biochemistry, and behavior
JID - 0367050
RN  - 0 (2-chloro-5-nitrobenzanilide)
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Anilides)
RN  - 0 (Benzimidazoles)
RN  - 0 (Benzoates)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - U5SYW473RQ (Telmisartan)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology
MH  - Anilides/pharmacology
MH  - Animals
MH  - Benzimidazoles/*pharmacology
MH  - Benzoates/*pharmacology
MH  - Body Weight/drug effects
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Corticosterone/blood
MH  - Exploratory Behavior/drug effects
MH  - Hippocampus/metabolism
MH  - Hypothalamo-Hypophyseal System/*physiology
MH  - Male
MH  - Memory Disorders/*prevention & control
MH  - Pituitary-Adrenal System/*physiology
MH  - Prefrontal Cortex/drug effects/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Stress, Psychological/*psychology
MH  - Telmisartan
MH  - Up-Regulation
OTO - NOTNLM
OT  - ARB
OT  - Angiotensin II
OT  - BDNF
OT  - GW9662
OT  - PPAR-gamma
OT  - Stress
OT  - Telmisartan
EDAT- 2016/07/05 06:00
MHDA- 2017/08/18 06:00
CRDT- 2016/07/05 06:00
PHST- 2016/02/15 00:00 [received]
PHST- 2016/06/10 00:00 [revised]
PHST- 2016/06/29 00:00 [accepted]
PHST- 2016/07/05 06:00 [entrez]
PHST- 2016/07/05 06:00 [pubmed]
PHST- 2017/08/18 06:00 [medline]
AID - S0091-3057(16)30110-1 [pii]
AID - 10.1016/j.pbb.2016.06.010 [doi]
PST - ppublish
SO  - Pharmacol Biochem Behav. 2016 Sep;148:108-18. doi: 10.1016/j.pbb.2016.06.010. 
      Epub 2016 Jul 1.