PMID- 37514044
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230801
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 15
IP  - 7
DP  - 2023 Jul 1
TI  - Dysregulation of Amino Acid Transporters in a Rat Model of TLR7-Mediated Maternal 
      Immune Activation.
LID - 10.3390/pharmaceutics15071857 [doi]
LID - 1857
AB  - Maternal immune activation (MIA) during pregnancy is linked to neurodevelopmental 
      disorders in humans. Similarly, the TLR7 agonist imiquimod alters 
      neurodevelopment in rodents. While the mechanisms underlying MIA-mediated 
      neurodevelopmental changes are unknown, they could involve dysregulation of amino 
      acid transporters essential for neurodevelopment. Therefore, we sought to 
      determine the nature of such transporter changes in both imiquimod-treated rats 
      and human placentas during infection. Pregnant rats received imiquimod on 
      gestational day (GD)14. Transporter expression was measured in placentas and 
      fetal brains via qPCR (GD14.5) and immunoblotting (GD16). To monitor function, 
      fetal brain amino acid levels were measured by HPLC on GD16. Gene expression in 
      the cortex of female fetal brains was further examined by RNAseq on GD19. In 
      human placentas, suspected active infection was associated with decreased ASCT1 
      and SNAT2 protein expression. Similarly, in imiquimod-treated rats, ASCT1 and 
      SNAT2 protein was also decreased in male placentas, while EAAT2 was decreased in 
      female placentas. CAT3 was increased in female fetal brains. Consistent with 
      this, imiquimod altered amino acid levels in fetal brains, while RNAseq 
      demonstrated changes in expression of several genes implicated in autism. Thus, 
      imiquimod alters amino acid transporter levels in pregnant rats, and similar 
      changes occur in human placentas during active infection. This suggests that 
      changes in expression of amino acid transporters may contribute to effects 
      mediated by MIA toward altered neurodevelopment.
FAU - McColl, Eliza R
AU  - McColl ER
AD  - Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University 
      of Toronto, 144 College St, Toronto, ON M5S 3M2, Canada.
FAU - Henderson, Jeffrey T
AU  - Henderson JT
AD  - Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University 
      of Toronto, 144 College St, Toronto, ON M5S 3M2, Canada.
FAU - Piquette-Miller, Micheline
AU  - Piquette-Miller M
AUID- ORCID: 0000-0002-3847-8224
AD  - Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University 
      of Toronto, 144 College St, Toronto, ON M5S 3M2, Canada.
LA  - eng
GR  - PJT-169195/CAPMC/CIHR/Canada
GR  - GSD-164238/CAPMC/CIHR/Canada
PT  - Journal Article
DEP - 20230701
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC10385561
OTO - NOTNLM
OT  - amino acid transporters
OT  - autism
OT  - infection
OT  - neurodevelopment
OT  - neurodevelopmental disorders
OT  - placenta
OT  - pregnancy
COIS- The authors declare no conflict of interest.
EDAT- 2023/07/29 11:45
MHDA- 2023/07/29 11:46
PMCR- 2023/07/01
CRDT- 2023/07/29 01:39
PHST- 2023/06/01 00:00 [received]
PHST- 2023/06/16 00:00 [revised]
PHST- 2023/06/26 00:00 [accepted]
PHST- 2023/07/29 11:46 [medline]
PHST- 2023/07/29 11:45 [pubmed]
PHST- 2023/07/29 01:39 [entrez]
PHST- 2023/07/01 00:00 [pmc-release]
AID - pharmaceutics15071857 [pii]
AID - pharmaceutics-15-01857 [pii]
AID - 10.3390/pharmaceutics15071857 [doi]
PST - epublish
SO  - Pharmaceutics. 2023 Jul 1;15(7):1857. doi: 10.3390/pharmaceutics15071857.