PMID- 33011197
OWN - NLM
STAT- MEDLINE
DCOM- 20211026
LR  - 20211026
IS  - 1873-2747 (Electronic)
IS  - 0361-9230 (Linking)
VI  - 165
DP  - 2020 Dec
TI  - Involvement of endoplasmic reticulum stress in amyloid beta ((1-42))-induced 
      Alzheimer's like neuropathological process in rat brain.
PG  - 108-117
LID - S0361-9230(20)30644-4 [pii]
LID - 10.1016/j.brainresbull.2020.09.022 [doi]
AB  - Amyloid-beta (Abeta) accumulation in the brain is a pathological hallmark of 
      Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress has been implicated 
      in aetiology of neurodegenerative disorders. We studied the involvement of ER 
      stress in Abeta-induced neuronal degeneration in rat brain to correlate it with 
      cellular and molecular modifications in Abeta-induced Alzheimer's like 
      neuropathological process. Abeta ((1-42)) (5 mug) was administered by bilateral 
      intracerebroventricular (icv) injection in the brain of adult male Wistar rats. 
      Acetylcholinesterase (AChE) activity and histological alterations were observed 
      in different brain regions. ER stress-associated proteins- glucose regulated 
      protein-78 (GRP78), eukaryotic translation initiation factor-2alpha (eIF2alpha) and 
      growth arrest and DNA damage-inducible protein-153 (GADD153), neuronal marker- 
      microtubule associated protein-2 (MAP-2) and microglial protein- ionized calcium 
      binding adaptor molecule-1 (Iba-1) were measured by western blot. Reduced 
      glutathione (GSH), nitrite level and levels of caspase-12 and caspase-3 were also 
      measured. ER stress inhibitor, salubrinal (1 mg/kg, intraperitoneally, ip) was 
      used to assess the specific role of ER stress. Abeta ((1-42))-induced increase in 
      AChE activity, GRP78 and GADD protein levels, dephosphorylation of eIF2-alpha and 
      caspase-12 and caspase-3 levels and decrease in GSH and MAP-2 levels were 
      attenuated by salubrinal. Increase in Iba-1 protein and nitrite levels after Abeta 
      ((1-42)) administration were partially attenuated by salubrinal. Abeta 
      ((1-42))-induced histological alterations were correlated with findings of ER 
      stress. Results of present study implicate ER stress as a potential molecular 
      mechanism in Abeta-induced Alzheimer's like neuropathology which could serve as 
      surrogate biomarker for study of AD progression and efficacy of therapeutic 
      interventions for AD management.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Goswami, Poonam
AU  - Goswami P
AD  - Molecular Toxicology Laboratory, Department of Medical Elementology and 
      Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
FAU - Afjal, Mohd Amir
AU  - Afjal MA
AD  - Molecular Toxicology Laboratory, Department of Medical Elementology and 
      Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
FAU - Akhter, Juheb
AU  - Akhter J
AD  - Molecular Toxicology Laboratory, Department of Medical Elementology and 
      Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
FAU - Mangla, Anuradha
AU  - Mangla A
AD  - Molecular Toxicology Laboratory, Department of Medical Elementology and 
      Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
FAU - Khan, Jasim
AU  - Khan J
AD  - Molecular Toxicology Laboratory, Department of Medical Elementology and 
      Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India; 
      Currently at the School of Medicine, University of Alabama at Birmingham, 
      Birmingham, Alabama 35233, USA.
FAU - Parvez, Suhel
AU  - Parvez S
AD  - Molecular Neurobiology Laboratory, Department of Medical Elementology and 
      Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
FAU - Raisuddin, Sheikh
AU  - Raisuddin S
AD  - Molecular Toxicology Laboratory, Department of Medical Elementology and 
      Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India. 
      Electronic address: sraisuddin@jamiahamdard.ac.in.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201001
PL  - United States
TA  - Brain Res Bull
JT  - Brain research bulletin
JID - 7605818
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (GRP78 protein, rat)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Nitrites)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Acetylcholinesterase/metabolism
MH  - Alzheimer Disease/*metabolism/pathology
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Brain/*metabolism/pathology
MH  - Endoplasmic Reticulum Stress/*physiology
MH  - Glutathione/metabolism
MH  - Heat-Shock Proteins/metabolism
MH  - Male
MH  - Neurons/*metabolism/pathology
MH  - Nitrites/metabolism
MH  - Oxidative Stress/physiology
MH  - Peptide Fragments/*metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Apoptosis
OT  - Glial activation
OT  - Oxidative stress
OT  - Salubrinal
OT  - Unfolded protein response
EDAT- 2020/10/05 06:00
MHDA- 2021/10/27 06:00
CRDT- 2020/10/04 20:22
PHST- 2020/04/24 00:00 [received]
PHST- 2020/09/10 00:00 [revised]
PHST- 2020/09/25 00:00 [accepted]
PHST- 2020/10/05 06:00 [pubmed]
PHST- 2021/10/27 06:00 [medline]
PHST- 2020/10/04 20:22 [entrez]
AID - S0361-9230(20)30644-4 [pii]
AID - 10.1016/j.brainresbull.2020.09.022 [doi]
PST - ppublish
SO  - Brain Res Bull. 2020 Dec;165:108-117. doi: 10.1016/j.brainresbull.2020.09.022. 
      Epub 2020 Oct 1.