PMID- 32601776
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20240226
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 41
IP  - 7
DP  - 2021 Oct
TI  - Roles and Interaction of the MAPK Signaling Cascade in Abeta25-35-Induced 
      Neurotoxicity Using an Isolated Primary Hippocampal Cell Culture System.
PG  - 1497-1507
LID - 10.1007/s10571-020-00912-4 [doi]
AB  - Alzheimer's disease (AD) is characterized with increased formation of amyloid-beta 
      (Abeta) in the brain. Abeta peptide toxicity is associated with disturbances of several 
      intracellular signaling pathways such as mitogen activated protein kinases 
      (MAPKs). The aim of this study was to investigate the role of MAPKs and their 
      interactions in Abeta-induced neurotoxicity using isolated hippocampal neurons from 
      the rat. Primary hippocampal cells were cultured in neurobasal medium for 4 days. 
      Cells were treated with Abeta25-35 and/or MAPKs inhibitors for 24 h. Cell viability 
      was determined by an MTT assay and phosphorylated levels of P38, JNK, and ERK 
      were measured by Western blots. Abeta treatment (10-40 microM) significantly decreased 
      hippocampal cell viability in a dose-dependent manner. Inhibition of P38 and ERK 
      did not restore cell viability, while JNK inhibition potentiated the Abeta-induced 
      neurotoxicity. Compared to the controls, Abeta treatment increased levels of 
      phosphorylated JNK, ERK, and c-Jun, while it had no effect on levels of 
      phosphorylated P38. In addition, P38 inhibition led to decreased expression 
      levels of phosphorylated ERK; inhibition of JNK resulted in decreased expression 
      of c-Jun; and inhibition of ERK, decreased phosphorylated levels of JNK. These 
      results strongly suggest that P38, ERK, and JNK are not independently involved in 
      Abeta-induced toxicity in the hippocampal cells. In AD, which is a multifactorial 
      disease, inhibiting a single member of the MAPK signaling pathway, does not seem 
      to be sufficient to mitigate Abeta-induced toxicity and thus their interactions with 
      each other or potentially with different signaling pathways should be taken into 
      account.
CI  - (c) 2020. Springer Science+Business Media, LLC, part of Springer Nature.
FAU - Iloun, Parisa
AU  - Iloun P
AD  - Physiology Department, School of Medicine, Shahid Beheshti University of Medical 
      Sciences, Tehran, Iran.
AD  - Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, 
      Tehran, Iran.
FAU - Hooshmandi, Etrat
AU  - Hooshmandi E
AD  - Clinical Neurology Research Center, Shiraz University of Medical Sciences, 
      Shiraz, Iran.
AD  - Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, 
      Velenjak, Chamran Exp. Way, P.O. Box 19615-1178, Tehran, Iran.
FAU - Gheibi, Sevda
AU  - Gheibi S
AD  - Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, 
      Tehran, Iran.
FAU - Kashfi, Khosrow
AU  - Kashfi K
AD  - Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of 
      Biomedical Education, City University of New York School of Medicine, New York, 
      USA.
FAU - Ghasemi, Rasoul
AU  - Ghasemi R
AUID- ORCID: 0000-0002-1394-6853
AD  - Physiology Department, School of Medicine, Shahid Beheshti University of Medical 
      Sciences, Tehran, Iran. rghasemi60@sbmu.ac.ir.
AD  - Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, 
      Tehran, Iran. rghasemi60@sbmu.ac.ir.
FAU - Ahmadiani, Abolhassan
AU  - Ahmadiani A
AD  - Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, 
      Velenjak, Chamran Exp. Way, P.O. Box 19615-1178, Tehran, Iran. 
      aahmadiani@yahoo.com.
LA  - eng
GR  - 958343/National Institute for Medical Research Development/
PT  - Journal Article
DEP - 20200629
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (25-35))
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Female
MH  - Hippocampus/*metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - MAP Kinase Signaling System/*physiology
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Neurons/metabolism
MH  - Neuroprotective Agents/pharmacology
MH  - Peptide Fragments/*metabolism
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects/physiology
MH  - Rats
OTO - NOTNLM
OT  - Alzheimer disease
OT  - Amyloid-beta
OT  - ERK
OT  - JNK
OT  - MAPK signaling pathway
OT  - P38
EDAT- 2020/07/01 06:00
MHDA- 2022/01/14 06:00
CRDT- 2020/07/01 06:00
PHST- 2020/01/29 00:00 [received]
PHST- 2020/06/22 00:00 [accepted]
PHST- 2020/07/01 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
PHST- 2020/07/01 06:00 [entrez]
AID - 10.1007/s10571-020-00912-4 [pii]
AID - 10.1007/s10571-020-00912-4 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2021 Oct;41(7):1497-1507. doi: 10.1007/s10571-020-00912-4. 
      Epub 2020 Jun 29.