PMID- 36454179
OWN - NLM
STAT- MEDLINE
DCOM- 20230405
LR  - 20230407
IS  - 2378-8763 (Electronic)
IS  - 2378-8763 (Linking)
VI  - 8
IP  - 2
DP  - 2023 Apr
TI  - Cannabidiol Protects Striatal Neurons by Attenuating Endoplasmic Reticulum 
      Stress.
PG  - 299-308
LID - 10.1089/can.2022.0090 [doi]
AB  - Introduction: The aggregation of misfolded proteins in the endoplasmic reticulum 
      (ER) is a pathological trait shared by many neurodegenerative disorders. This 
      aggregation leads to the persistent activation of the unfolded protein response 
      (UPR) and ultimately apoptosis as a result of ER stress. Cannabidiol (CBD) has 
      been demonstrated to be neuroprotective in various cellular and animal models of 
      neurodegeneration, which has been attributed to its antioxidant and 
      anti-inflammatory properties. However, little is known about the role of CBD in 
      the context of protein folding and ER stress. The purpose of this study was to 
      investigate whether CBD is neuroprotective against an in vitro model of ER 
      stress. Materials and Methods: Using different exposure models, mouse striatal 
      STHdh(Q7/Q7) cells were exposed to either the ER stress inducer thapsigargin (TG) 
      and/or CBD. Cell viabilities assays were used to investigate the effect of CBD 
      pre-treatment, co-treatment, and post-treatment on TG-induced cell death. 
      Real-time quantitative polymerase chain reaction was used to measure changes in 
      ER stress regulators and UPR genes such as glucose-regulated protein-78 (GRP78), 
      mesencephalic astrocyte-derived neurotrophic factor (MANF), B cell lymphoma 2 
      (BCL-2), BCL-2 interacting mediator of cell death (BIM), and caspase-12. Results: 
      Cell viability increased significantly when cells were pre-treated with CBD 
      before TG exposure. An increase in the gene expression of pro-survival ER 
      chaperone GRP78 and ER-resident neurotrophic factor MANF coincided with this 
      effect and decreased ER-mediated pro-apoptotic markers such as BIM, and 
      caspase-12 was observed. Conclusions: These data suggest that CBD pre-treatment 
      is neuroprotective against TG-induced cell death. Understanding the role of ER 
      stress in CBD-driven neuroprotection provides insight into the therapeutic 
      potential of CBD and the role of ER dysfunction in neurodegenerative disorders.
FAU - Patel, Vidhi
AU  - Patel V
AUID- ORCID: 0000-0001-6890-6528
AD  - Department of Psychiatry and Behavioural Neurosciences, McMaster University, 
      Hamilton, Ontario, Canada.
FAU - Abu-Hijleh, Fahed
AU  - Abu-Hijleh F
AD  - Department of Psychiatry and Behavioural Neurosciences, McMaster University, 
      Hamilton, Ontario, Canada.
FAU - Rigg, Nicolette
AU  - Rigg N
AD  - Department of Psychiatry and Behavioural Neurosciences, McMaster University, 
      Hamilton, Ontario, Canada.
FAU - Mishra, Ram
AU  - Mishra R
AD  - Department of Psychiatry and Behavioural Neurosciences, McMaster University, 
      Hamilton, Ontario, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221128
PL  - United States
TA  - Cannabis Cannabinoid Res
JT  - Cannabis and cannabinoid research
JID - 101684827
RN  - 19GBJ60SN5 (Cannabidiol)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - EC 3.4.22.- (Caspase 12)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (MANF protein, mouse)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Cannabidiol/pharmacology
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Caspase 12
MH  - Endoplasmic Reticulum Stress
MH  - Nerve Growth Factors/genetics/metabolism/pharmacology
MH  - Neurons
MH  - Proto-Oncogene Proteins c-bcl-2/pharmacology
OTO - NOTNLM
OT  - cannabidiol
OT  - endoplasmic reticulum stress
OT  - neuroprotection
OT  - thapsigargin
OT  - unfolded protein response
EDAT- 2022/12/02 06:00
MHDA- 2023/04/05 06:42
CRDT- 2022/12/01 10:33
PHST- 2023/04/05 06:42 [medline]
PHST- 2022/12/02 06:00 [pubmed]
PHST- 2022/12/01 10:33 [entrez]
AID - 10.1089/can.2022.0090 [doi]
PST - ppublish
SO  - Cannabis Cannabinoid Res. 2023 Apr;8(2):299-308. doi: 10.1089/can.2022.0090. Epub 
      2022 Nov 28.