PMID- 33775777
OWN - NLM
STAT- MEDLINE
DCOM- 20220124
LR  - 20220124
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 408
DP  - 2021 Jun 25
TI  - Imipramine alleviates memory impairment and hippocampal apoptosis in STZ-induced 
      sporadic Alzheimer's rat model: Possible contribution of MAPKs and insulin 
      signaling.
PG  - 113260
LID - S0166-4328(21)00148-0 [pii]
LID - 10.1016/j.bbr.2021.113260 [doi]
AB  - Alzheimer's disease (AD) is the most common age-related neurodegenerative 
      disease, associated with several pathophysiological complaints. Impaired insulin 
      signaling in the brain, is one of the important characteristic features of AD 
      which is accompanied by cognitive deficits. According to the multifactorial and 
      complicated pathology of AD, no modifying therapy has been approved yet. 
      Imipramine is a kind of tricyclic antidepressant with reported anti-inflammatory 
      and anti-oxidant effects in the brain. There are controversial studies about the 
      effect of this drug on spatial memory. This study investigates the effect of 
      imipramine on streptozotocin (STZ) induced memory impairment in rats. Pursuing 
      this objective, rats were treated with imipramine 10 or 20 mg/kg i.p. once a day 
      for 14 days. 24 h after the last injection, memory function was evaluated by the 
      Morris water maze (MWM) test in 4 consecutive days. Then, hippocampi were removed 
      and the activity of caspase-3, mitogen activated protein kinases (MAPKs) family 
      and inhibitory phosphorylation of insulin receptor substrate-1 (IRS-1(ser307)) 
      were analyzed using Western blotting. Results showed that imipramine prevents 
      memory impairment in STZ induced rats and this improvement was accompanied with 
      an increase in ERK activity, reduction of caspase-3 and JNK activity, as well as 
      partial restoration of P38 and IRS-1 activity. In conclusion, our study 
      demonstrated that at least some members of the MAPK family are involved in the 
      neuroprotective effect of imipramine.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Javadpour, Pegah
AU  - Javadpour P
AD  - Department of Physiology, Faculty of Medicine, Shahid Beheshti University of 
      Medical Sciences, Tehran, Iran; Neurophysiology Research Center, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran.
FAU - Askari, Sahar
AU  - Askari S
AD  - Department of Physiology, Faculty of Medicine, Shahid Beheshti University of 
      Medical Sciences, Tehran, Iran; Neurophysiology Research Center, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran.
FAU - Rashidi, Fatemeh Sadat
AU  - Rashidi FS
AD  - Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, 
      Tehran, Iran.
FAU - Dargahi, Leila
AU  - Dargahi L
AD  - Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, 
      Tehran, Iran.
FAU - Ahmadiani, Abolhassan
AU  - Ahmadiani A
AD  - Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, 
      Tehran, Iran.
FAU - Ghasemi, Rasoul
AU  - Ghasemi R
AD  - Department of Physiology, Faculty of Medicine, Shahid Beheshti University of 
      Medical Sciences, Tehran, Iran; Neurophysiology Research Center, Shahid Beheshti 
      University of Medical Sciences, Tehran, Iran. Electronic address: 
      Rghasemi60@sbmu.ac.ir.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210326
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Insulin)
RN  - 5W494URQ81 (Streptozocin)
RN  - OGG85SX4E4 (Imipramine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/*pharmacology
MH  - Alzheimer Disease/chemically induced/*drug therapy/metabolism
MH  - Animals
MH  - Antibiotics, Antineoplastic/pharmacology
MH  - Behavior, Animal/drug effects
MH  - Disease Models, Animal
MH  - Hippocampus/*drug effects/metabolism
MH  - Imipramine/*pharmacology
MH  - Insulin/*metabolism
MH  - MAP Kinase Signaling System/*drug effects
MH  - Male
MH  - Memory Disorders/chemically induced/*drug therapy/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Streptozocin/pharmacology
OTO - NOTNLM
OT  - Imipramine
OT  - Insulin receptor substrate proteins
OT  - MAP kinase signaling system
OT  - Memory disorders
OT  - Streptozotocin
EDAT- 2021/03/30 06:00
MHDA- 2022/01/27 06:00
CRDT- 2021/03/29 05:55
PHST- 2020/12/23 00:00 [received]
PHST- 2021/02/11 00:00 [revised]
PHST- 2021/03/20 00:00 [accepted]
PHST- 2021/03/30 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/03/29 05:55 [entrez]
AID - S0166-4328(21)00148-0 [pii]
AID - 10.1016/j.bbr.2021.113260 [doi]
PST - ppublish
SO  - Behav Brain Res. 2021 Jun 25;408:113260. doi: 10.1016/j.bbr.2021.113260. Epub 
      2021 Mar 26.