PMID- 36171057
OWN - NLM
STAT- MEDLINE
DCOM- 20221012
LR  - 20221214
IS  - 2373-2822 (Electronic)
IS  - 2373-2822 (Linking)
VI  - 9
IP  - 5
DP  - 2022 Sep-Oct
TI  - Prenatal THC Exposure Induces Sex-Dependent Neuropsychiatric Endophenotypes in 
      Offspring and Long-Term Disruptions in Fatty-Acid Signaling Pathways Directly in 
      the Mesolimbic Circuitry.
LID - ENEURO.0253-22.2022 [pii]
LID - 10.1523/ENEURO.0253-22.2022 [doi]
AB  - Despite increased prevalence of maternal cannabis use, little is understood 
      regarding potential long-term effects of prenatal cannabis exposure (PCE) on 
      neurodevelopmental outcomes. While neurodevelopmental cannabis exposure increases 
      the risk of developing affective/mood disorders in adulthood, the precise 
      neuropathophysiological mechanisms in male and female offspring are largely 
      unknown. Given the interconnectivity of the endocannabinoid (ECb) system and the 
      brain's fatty acid pathways, we hypothesized that prenatal exposure to 
      Delta(9)-tetrahydrocannabinol (THC) may dysregulate fetal neurodevelopment through 
      alterations of fatty-acid dependent synaptic and neuronal function in the 
      mesolimbic system. To investigate this, pregnant Wistar rats were exposed to 
      vehicle or THC (3 mg/kg) from gestational day (GD)7 until GD22. Anxiety-like, 
      depressive-like, and reward-seeking behavior, electrophysiology, and molecular 
      assays were performed on adult male/female offspring. Imaging of fatty acids 
      using matrix-assisted laser desorption/ionization imaging mass spectrometry 
      (MALDI IMS) was performed at prepubescence and adulthood. We report that PCE 
      induces behavioral, neuronal, and molecular alterations in the mesolimbic system 
      in male and female offspring, resembling neuropsychiatric endophenotypes. 
      Additionally, PCE resulted in profound dysregulation of critical fatty acid 
      pathways in the developing brain lipidome. Female progeny exhibited significant 
      alterations to fatty acid levels at prepubescence but recovered from these 
      deficits by early adulthood. In contrast, males exhibited persistent fatty acid 
      deficits into adulthood. Moreover, both sexes maintained enduring abnormalities 
      in glutamatergic/GABAergic function in the nucleus accumbens (NAc). These 
      findings identify several novel long-term risks of maternal cannabis use and 
      demonstrate for the first time, sex-related effects of maternal cannabinoid 
      exposure directly in the developing neural lipidome.
CI  - Copyright (c) 2022 Sarikahya et al.
FAU - Sarikahya, Mohammed H
AU  - Sarikahya MH
AUID- ORCID: 0000-0002-5511-2638
AD  - Addiction Research Group, Schulich School of Medicine and Dentistry, Western 
      University, London, Ontario N6A 5C1, Canada.
AD  - Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 
      3K7, Canada.
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
FAU - Cousineau, Samantha
AU  - Cousineau S
AD  - Departments of Biochemistry and Chemistry, Western University, London, Ontario 
      N6A 5C1, Canada.
FAU - De Felice, Marta
AU  - De Felice M
AD  - Addiction Research Group, Schulich School of Medicine and Dentistry, Western 
      University, London, Ontario N6A 5C1, Canada.
AD  - Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 
      3K7, Canada.
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
FAU - Lee, Kendrick
AU  - Lee K
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
AD  - Departments of Physiology and Pharmacology and Obstetrics and Gynaecology, 
      Western University, London, Ontario N6A 5C1, Canada.
AD  - St. Josephs Health Care, Children's Health Research Institute, London, Ontario 
      N6C 2R5, Canada.
FAU - Wong, Karen Kw
AU  - Wong KK
AD  - Addiction Research Group, Schulich School of Medicine and Dentistry, Western 
      University, London, Ontario N6A 5C1, Canada.
AD  - Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 
      3K7, Canada.
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
FAU - DeVuono, Marieka V
AU  - DeVuono MV
AD  - Addiction Research Group, Schulich School of Medicine and Dentistry, Western 
      University, London, Ontario N6A 5C1, Canada.
AD  - Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 
      3K7, Canada.
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
FAU - Jung, Tony
AU  - Jung T
AD  - Addiction Research Group, Schulich School of Medicine and Dentistry, Western 
      University, London, Ontario N6A 5C1, Canada.
AD  - Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 
      3K7, Canada.
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
FAU - Rodriguez-Ruiz, Mar
AU  - Rodriguez-Ruiz M
AD  - Addiction Research Group, Schulich School of Medicine and Dentistry, Western 
      University, London, Ontario N6A 5C1, Canada.
AD  - Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 
      3K7, Canada.
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
FAU - Ng, Tsun Hay Jason
AU  - Ng THJ
AD  - Addiction Research Group, Schulich School of Medicine and Dentistry, Western 
      University, London, Ontario N6A 5C1, Canada.
AD  - Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 
      3K7, Canada.
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
FAU - Gummerson, Dana
AU  - Gummerson D
AD  - Addiction Research Group, Schulich School of Medicine and Dentistry, Western 
      University, London, Ontario N6A 5C1, Canada.
AD  - Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 
      3K7, Canada.
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
FAU - Proud, Emma
AU  - Proud E
AD  - Addiction Research Group, Schulich School of Medicine and Dentistry, Western 
      University, London, Ontario N6A 5C1, Canada.
AD  - Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 
      3K7, Canada.
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
FAU - Hardy, Daniel B
AU  - Hardy DB
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
AD  - Departments of Physiology and Pharmacology and Obstetrics and Gynaecology, 
      Western University, London, Ontario N6A 5C1, Canada.
AD  - St. Josephs Health Care, Children's Health Research Institute, London, Ontario 
      N6C 2R5, Canada.
FAU - Yeung, Ken K-C
AU  - Yeung KK
AD  - Departments of Biochemistry and Chemistry, Western University, London, Ontario 
      N6A 5C1, Canada.
FAU - Rushlow, Walter
AU  - Rushlow W
AD  - Addiction Research Group, Schulich School of Medicine and Dentistry, Western 
      University, London, Ontario N6A 5C1, Canada.
AD  - Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 
      3K7, Canada.
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
AD  - Department of Psychiatry, Western University, London, Ontario N6A 3K7, Canada.
FAU - Laviolette, Steven R
AU  - Laviolette SR
AD  - Addiction Research Group, Schulich School of Medicine and Dentistry, Western 
      University, London, Ontario N6A 5C1, Canada steven.laviolette@schulich.uwo.ca.
AD  - Department of Anatomy and Cell Biology, Western University, London, Ontario N6A 
      3K7, Canada.
AD  - St. Josephs Health Care, Lawson Health Research Institute, London, Ontario N6C 
      2R5, Canada.
AD  - Department of Psychiatry, Western University, London, Ontario N6A 3K7, Canada.
LA  - eng
GR  - PJT-159586/CIHR/Canada
GR  - CRU1126/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221010
PL  - United States
TA  - eNeuro
JT  - eNeuro
JID - 101647362
RN  - 0 (Cannabinoid Receptor Agonists)
RN  - 0 (Cannabinoids)
RN  - 0 (Endocannabinoids)
RN  - 0 (Fatty Acids)
RN  - 7J8897W37S (Dronabinol)
SB  - IM
MH  - Animals
MH  - Cannabinoid Receptor Agonists
MH  - *Cannabinoids
MH  - Dronabinol/toxicity
MH  - Endocannabinoids
MH  - Endophenotypes
MH  - Fatty Acids
MH  - Female
MH  - Humans
MH  - Male
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction
PMC - PMC9557330
OTO - NOTNLM
OT  - MALDI IMS
OT  - electrophysiology
OT  - lipidomics
OT  - mesolimbic system
OT  - prenatal cannabis exposure
OT  - sex differences
EDAT- 2022/09/29 06:00
MHDA- 2022/10/13 06:00
PMCR- 2022/10/07
CRDT- 2022/09/28 21:12
PHST- 2022/06/27 00:00 [received]
PHST- 2022/08/02 00:00 [revised]
PHST- 2022/08/22 00:00 [accepted]
PHST- 2022/09/29 06:00 [pubmed]
PHST- 2022/10/13 06:00 [medline]
PHST- 2022/09/28 21:12 [entrez]
PHST- 2022/10/07 00:00 [pmc-release]
AID - ENEURO.0253-22.2022 [pii]
AID - eN-NWR-0253-22 [pii]
AID - 10.1523/ENEURO.0253-22.2022 [doi]
PST - epublish
SO  - eNeuro. 2022 Oct 10;9(5):ENEURO.0253-22.2022. doi: 10.1523/ENEURO.0253-22.2022. 
      Print 2022 Sep-Oct.