PMID- 30564080
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1611-2156 (Print)
IS  - 1611-2156 (Electronic)
IS  - 1611-2156 (Linking)
VI  - 17
DP  - 2018
TI  - Everolimus, a mammalian target of rapamycin inhibitor, ameliorated 
      streptozotocin-induced learning and memory deficits via neurochemical alterations 
      in male rats.
PG  - 999-1017
LID - 10.17179/excli2018-1626 [doi]
AB  - Everolimus (EVR), as a rapamycin analog, is a selective inhibitor of the 
      mammalian target of rapamycin (mTOR) kinase and its associated signaling pathway. 
      mTOR is a serine/threonine protein kinase and its hyperactivity is involved in 
      the pathophysiology of Alzheimer's disease (AD) and associated cognitive 
      deficits. The present study evaluated the impact of EVR, on cognitive functions, 
      hippocampal cell loss, and neurochemical parameters in the 
      intracerebroventricular streptozotocin (icv-STZ) model of AD rats. EVR (1 and 5 
      mg/kg) was administered for 21 days following the single administration of STZ (3 
      mg/kg, icv) or for 7 days on days 21-28 post-STZ injection after establishment of 
      cognitive dysfunction. Cognitive deficits (passive avoidance and spatial memory), 
      oxidative stress parameters, acetylcholinesterase (AChE) activity, and percentage 
      of cell loss were evaluated in the hippocampus. Chronic administration (1 and 5 
      mg/kg for 21 days from the day of surgery and icv-STZ infusion) or acute 
      injection (5 mg/kg for 7 days after establishment of cognitive impairment) of EVR 
      significantly attenuated cognitive dysfunction, neuronal loss, oxidative stress 
      and AChE activity in the hippocampus of STZ-AD rats. In conclusion, our study 
      showed that EVR could prevent or improve deteriorations in behavioral, 
      biochemical and histopathological features of the icv-STZ rat model of AD. 
      Therefore, inhibition of the hyperactivated mTOR may be an important therapeutic 
      target for AD.
FAU - Fanoudi, Sahar
AU  - Fanoudi S
AD  - Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical 
      Sciences, Mashhad, Iran.
AD  - Pharmacological Research Center of Medicinal Plants, Mashhad University of 
      Medical Sciences, Mashhad, Iran.
FAU - Hosseini, Mahmoud
AU  - Hosseini M
AD  - Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research 
      Center, Mashhad University of Medical Sciences, Mashhad, Iran.
FAU - Alavi, Mohaddeseh Sadat
AU  - Alavi MS
AD  - Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical 
      Sciences, Mashhad, Iran.
AD  - Pharmacological Research Center of Medicinal Plants, Mashhad University of 
      Medical Sciences, Mashhad, Iran.
FAU - Boroushaki, Mohammad Taher
AU  - Boroushaki MT
AD  - Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical 
      Sciences, Mashhad, Iran.
AD  - Pharmacological Research Center of Medicinal Plants, Mashhad University of 
      Medical Sciences, Mashhad, Iran.
FAU - Hosseini, Azar
AU  - Hosseini A
AD  - Pharmacological Research Center of Medicinal Plants, Mashhad University of 
      Medical Sciences, Mashhad, Iran.
FAU - Sadeghnia, Hamid R
AU  - Sadeghnia HR
AD  - Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical 
      Sciences, Mashhad, Iran.
AD  - Pharmacological Research Center of Medicinal Plants, Mashhad University of 
      Medical Sciences, Mashhad, Iran.
AD  - Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research 
      Center, Mashhad University of Medical Sciences, Mashhad, Iran.
LA  - eng
PT  - Journal Article
DEP - 20181029
PL  - Germany
TA  - EXCLI J
JT  - EXCLI journal
JID - 101299402
PMC - PMC6295637
OTO - NOTNLM
OT  - Alzheimer's disease (AD)
OT  - acetylcholinesterase
OT  - everolimus
OT  - mTOR
OT  - oxidative stress
OT  - streptozotocin
EDAT- 2018/12/20 06:00
MHDA- 2018/12/20 06:01
PMCR- 2018/10/29
CRDT- 2018/12/20 06:00
PHST- 2018/08/16 00:00 [received]
PHST- 2018/10/05 00:00 [accepted]
PHST- 2018/12/20 06:00 [entrez]
PHST- 2018/12/20 06:00 [pubmed]
PHST- 2018/12/20 06:01 [medline]
PHST- 2018/10/29 00:00 [pmc-release]
AID - 2018-1626 [pii]
AID - Doc999 [pii]
AID - 10.17179/excli2018-1626 [doi]
PST - epublish
SO  - EXCLI J. 2018 Oct 29;17:999-1017. doi: 10.17179/excli2018-1626. eCollection 2018.