PMID- 37772463
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20240519
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 101
IP  - 12
DP  - 2023 Dec
TI  - Increased hippocampal cannabinoid 1 receptor expression is associated with 
      protection from severe seizures in pregnant mice with reduced uterine perfusion 
      pressure.
PG  - 1884-1899
LID - 10.1002/jnr.25244 [doi]
AB  - Eclampsia, new-onset seizures in pregnancy, can complicate preeclampsia, a 
      hypertensive pregnancy disorder. The mechanisms contributing to increased risk of 
      seizures in preeclampsia are not fully known. One mechanism could be abnormal 
      endocannabinoid system (ECS) activity and impaired neuromodulation. Indeed, 
      increased placental cannabinoid receptor 1 (CB1R) expression and reduced serum 
      anandamide, a CB1R ligand, have been reported in preeclampsia patients. We 
      hypothesized that reduced uterine perfusion pressure (RUPP), used to mimic 
      preeclampsia, leads to changes in hippocampal CB1R expression, and that 
      manipulating CB1R activity will change seizure severity in RUPP mice. Pregnant 
      mice underwent sham or RUPP surgery on gestational day (GD)13.5. On GD18.5, mice 
      received: no drug treatment, pentylenetetrazol (PTZ, 40 mg/kg), Rimonabant 
      (10 mg/kg) + PTZ, or 2-AG (1 mg/kg) + PTZ. Behaviors were video recorded (15 min 
      for Rimonabant and 2-AG, followed by 30 min for PTZ), and the hippocampus was 
      harvested. The expression of CB1R and ECS proteins was measured in hippocampal 
      homogenates, synaptosomes, and cytosol. Hippocampal CB1R increased in homogenates 
      and cytosolic fraction, and was unchanged in synaptosomes of RUPP mice. Increased 
      CB1R colocalization on glutamate-releasing neurons within hippocampal CA1 was 
      observed in RUPP mice. Rimonabant modestly increased seizure scores over time in 
      RUPP mice. PTZ after rimonabant pretreatment increased seizure scores and 
      duration, while reducing latency in sham mice, with little to no change in RUPP 
      mice. Furthermore, RUPP mice had lower seizure scores over time than sham 
      following CB1R blockade and activation. These data suggest that RUPP modifies 
      CB1R activity prior to seizure induction, which protects mice from worse seizure 
      outcomes.
CI  - (c) 2023 Wiley Periodicals LLC.
FAU - Jones-Muhammad, Maria
AU  - Jones-Muhammad M
AD  - Program in Neuroscience, University of Mississippi Medical School, Jackson, 
      Mississippi, USA.
FAU - Pryor, Tyranny
AU  - Pryor T
AD  - Department of Neurology, University of Mississippi Medical School, Jackson, 
      Mississippi, USA.
FAU - Shao, Qingmei
AU  - Shao Q
AD  - Department of Neurology, University of Mississippi Medical School, Jackson, 
      Mississippi, USA.
FAU - Freeman, Kevin B
AU  - Freeman KB
AD  - Department of Psychiatry and Human Behavior, University of Mississippi Medical 
      School, Jackson, Mississippi, USA.
FAU - Warrington, Junie P
AU  - Warrington JP
AUID- ORCID: 0000-0001-5626-8872
AD  - Department of Neurology, University of Mississippi Medical School, Jackson, 
      Mississippi, USA.
LA  - eng
GR  - R25 HL145817/HL/NHLBI NIH HHS/United States
GR  - R56 HL159447/HL/NHLBI NIH HHS/United States
GR  - P30 GM103328/GM/NIGMS NIH HHS/United States
GR  - F99 NS129125/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230929
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Cannabinoids)
RN  - RML78EN3XE (Rimonabant)
RN  - 0 (Receptors, Cannabinoid)
SB  - IM
EIN - J Neurosci Res. 2024 Apr;102(4):e25326. PMID: 38629284
MH  - Humans
MH  - Rats
MH  - Mice
MH  - Pregnancy
MH  - Animals
MH  - Female
MH  - *Pre-Eclampsia
MH  - Placenta
MH  - Rats, Sprague-Dawley
MH  - *Cannabinoids
MH  - Rimonabant/pharmacology
MH  - Receptors, Cannabinoid
MH  - Disease Models, Animal
MH  - Seizures/chemically induced
MH  - *Hypertension
MH  - Blood Pressure/physiology
MH  - Perfusion
MH  - Ischemia
OTO - NOTNLM
OT  - eclampsia
OT  - endocannabinoid system
OT  - pregnancy
OT  - seizure
OT  - synaptosomes
EDAT- 2023/09/29 06:43
MHDA- 2023/12/17 09:45
CRDT- 2023/09/29 05:33
PHST- 2023/08/11 00:00 [revised]
PHST- 2023/06/19 00:00 [received]
PHST- 2023/09/04 00:00 [accepted]
PHST- 2023/12/17 09:45 [medline]
PHST- 2023/09/29 06:43 [pubmed]
PHST- 2023/09/29 05:33 [entrez]
AID - 10.1002/jnr.25244 [doi]
PST - ppublish
SO  - J Neurosci Res. 2023 Dec;101(12):1884-1899. doi: 10.1002/jnr.25244. Epub 2023 Sep 
      29.