PMID- 35347586
OWN - NLM
STAT- MEDLINE
DCOM- 20220531
LR  - 20220718
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 59
IP  - 6
DP  - 2022 Jun
TI  - Inflammation and Nitro-oxidative Stress as Drivers of Endocannabinoid System 
      Aberrations in Mood Disorders and Schizophrenia.
PG  - 3485-3503
LID - 10.1007/s12035-022-02800-y [doi]
AB  - The endocannabinoid system (ECS) is composed of the endocannabinoid ligands 
      anandamide (AEA) and 2-arachidonoylgycerol (2-AG), their target cannabinoid 
      receptors (CB(1) and CB(2)) and the enzymes involved in their synthesis and 
      metabolism (N-acyltransferase and fatty acid amide hydrolase (FAAH) in the case 
      of AEA and diacylglycerol lipase (DAGL) and monoacylglycerol lipase (MAGL) in the 
      case of 2-AG). The origins of ECS dysfunction in major neuropsychiatric disorders 
      remain to be determined, and this paper explores the possibility that they may be 
      associated with chronically increased nitro-oxidative stress and activated 
      immune-inflammatory pathways, and it examines the mechanisms which might be 
      involved. Inflammation and nitro-oxidative stress are associated with both 
      increased CB(1) expression, via increased activity of the NADPH oxidases NOX4 and 
      NOX1, and increased CNR1 expression and DNA methylation; and CB(2) upregulation 
      via increased pro-inflammatory cytokine levels, binding of the transcription 
      factor Nrf2 to an antioxidant response element in the CNR2 promoter region and 
      the action of miR-139. CB(1) and CB(2) have antagonistic effects on redox 
      signalling, which may result from a miRNA-enabled negative feedback loop. The 
      effects of inflammation and oxidative stress are detailed in respect of AEA and 
      2-AG levels, via effects on calcium homeostasis and phospholipase A(2) activity; 
      on FAAH activity, via nitrosylation/nitration of functional cysteine and/or 
      tyrosine residues; and on 2-AG activity via effects on MGLL expression and MAGL. 
      Finally, based on these detailed molecular neurobiological mechanisms, it is 
      suggested that cannabidiol and dimethyl fumarate may have therapeutic potential 
      for major depressive disorder, bipolar disorder and schizophrenia.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Morris, Gerwyn
AU  - Morris G
AD  - IMPACT - the Institute for Mental and Physical Health and Clinical Translation, 
      School of Medicine, Barwon Health, Deakin University, Geelong, Australia.
FAU - Sominsky, Luba
AU  - Sominsky L
AD  - IMPACT - the Institute for Mental and Physical Health and Clinical Translation, 
      School of Medicine, Barwon Health, Deakin University, Geelong, Australia.
FAU - Walder, Kenneth R
AU  - Walder KR
AD  - IMPACT - the Institute for Mental and Physical Health and Clinical Translation, 
      School of Medicine, Barwon Health, Deakin University, Geelong, Australia.
FAU - Berk, Michael
AU  - Berk M
AD  - IMPACT - the Institute for Mental and Physical Health and Clinical Translation, 
      School of Medicine, Barwon Health, Deakin University, Geelong, Australia.
AD  - Orygen, The National Centre of Excellence in Youth Mental Health, Centre for 
      Youth Mental Health, Florey Institute for Neuroscience and Mental Health and the 
      Department of Psychiatry, The University of Melbourne, Melbourne, Australia.
FAU - Marx, Wolfgang
AU  - Marx W
AD  - IMPACT - the Institute for Mental and Physical Health and Clinical Translation, 
      School of Medicine, Barwon Health, Deakin University, Geelong, Australia.
FAU - Carvalho, Andre F
AU  - Carvalho AF
AD  - Campbell Family Mental Health Research Institute, CAMH, 33 Ursula Franklin 
      Street, Toronto, ON, Canada.
AD  - Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
AD  - Deakin University, Victoria, Australia.
FAU - Bortolasci, Chiara C
AU  - Bortolasci CC
AD  - IMPACT - the Institute for Mental and Physical Health and Clinical Translation, 
      School of Medicine, Barwon Health, Deakin University, Geelong, Australia.
FAU - Maes, Michael
AU  - Maes M
AD  - IMPACT - the Institute for Mental and Physical Health and Clinical Translation, 
      School of Medicine, Barwon Health, Deakin University, Geelong, Australia.
AD  - Department of Psychiatry, Faculty of Medicine, King Chulalongkorn Memorial 
      Hospital, Bangkok, Thailand.
AD  - Department of Psychiatry, Medical University of Plovdiv, Plovdiv, Bulgaria.
FAU - Puri, Basant K
AU  - Puri BK
AUID- ORCID: 0000-0001-6101-0139
AD  - University of Winchester and C.A.R, Cambridge, UK. bpuri@cantab.net.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220326
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Endocannabinoids)
RN  - 0 (MIRN139 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - EC 3.1.1.23 (Monoacylglycerol Lipases)
RN  - EC 3.5.- (Amidohydrolases)
SB  - IM
MH  - Amidohydrolases/metabolism
MH  - *Depressive Disorder, Major
MH  - Endocannabinoids/metabolism
MH  - Humans
MH  - Inflammation
MH  - *MicroRNAs/metabolism
MH  - Monoacylglycerol Lipases/metabolism
MH  - Oxidative Stress
MH  - Receptor, Cannabinoid, CB1/genetics/metabolism
MH  - *Schizophrenia
OTO - NOTNLM
OT  - Bipolar disorder
OT  - Cannabidiol
OT  - Dimethyl fumarate
OT  - Endocannabinoid system
OT  - Major depressive disorder
OT  - Schizophrenia
EDAT- 2022/03/30 06:00
MHDA- 2022/06/01 06:00
CRDT- 2022/03/29 05:48
PHST- 2021/03/08 00:00 [received]
PHST- 2022/03/13 00:00 [accepted]
PHST- 2022/03/30 06:00 [pubmed]
PHST- 2022/06/01 06:00 [medline]
PHST- 2022/03/29 05:48 [entrez]
AID - 10.1007/s12035-022-02800-y [pii]
AID - 10.1007/s12035-022-02800-y [doi]
PST - ppublish
SO  - Mol Neurobiol. 2022 Jun;59(6):3485-3503. doi: 10.1007/s12035-022-02800-y. Epub 
      2022 Mar 26.