PMID- 27746712
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210109
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 10
DP  - 2016
TI  - N-Methyl D-Aspartate Receptor Antagonist Kynurenic Acid Affects Human Cortical 
      Development.
PG  - 435
LID - 435
AB  - Kynurenic acid (KYNA), a neuroactive metabolite of tryptophan degradation, acts 
      as an endogenous N-methyl-D-aspartate receptor (NMDAR) antagonist. Elevated 
      levels of KYNA have been observed in pregnant women after viral infections and 
      are considered to play a role in neurodevelopmental disorders. However, the 
      consequences of KYNA-induced NMDAR blockade in human cortical development still 
      remain elusive. To study the potential impact of KYNA on human neurodevelopment, 
      we used an in vitro system of multipotent cortical progenitors, i.e., radial glia 
      cells (RGCs), enriched from human cerebral cortex at mid-gestation (16-19 
      gestational weeks). KYNA treatment significantly decreased RGCs proliferation and 
      survival by antagonizing NMDAR. This alteration resulted in a reduced number of 
      cortical progenitors and neurons while number and activation of astrocytes 
      increased. KYNA treatment reduced differentiation of RGCs into GABAergic neurons, 
      while differentiation into glutamatergic neurons was relatively spared. 
      Furthermore, in mixed cortical cultures KYNA triggered an inflammatory response 
      as evidenced by increased levels of the pro-inflammatory cytokine IL-6. In 
      conclusion, elevated levels of KYNA play a significant role in human RGC fate 
      determination by antagonizing NMDARs and by activating an inflammatory response. 
      The altered cell composition observed in cell culture following exposure to 
      elevated KYNA levels suggests a mechanism for impairment of cortical circuitry 
      formation in the fetal brain after viral infection, as seen in neurodevelopmental 
      disorders such as schizophrenia.
FAU - Bagasrawala, Inseyah
AU  - Bagasrawala I
AD  - Department of Neuroscience, University of Connecticut Health Farmington, CT, USA.
FAU - Zecevic, Nada
AU  - Zecevic N
AD  - Department of Neuroscience, University of Connecticut Health Farmington, CT, USA.
FAU - Radonjic, Nevena V
AU  - Radonjic NV
AD  - Department of Psychiatry, University of Connecticut Health Farmington, CT, USA.
LA  - eng
GR  - G0700089/MRC_/Medical Research Council/United Kingdom
GR  - R37 DA023999/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20160930
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC5043058
OTO - NOTNLM
OT  - KYNA
OT  - NMDARs
OT  - cerebral cortex
OT  - cortical progenitor cells
OT  - human fetal brain
OT  - neurogenesis
OT  - tissue culture
EDAT- 2016/10/18 06:00
MHDA- 2016/10/18 06:01
PMCR- 2016/01/01
CRDT- 2016/10/18 06:00
PHST- 2016/06/06 00:00 [received]
PHST- 2016/09/08 00:00 [accepted]
PHST- 2016/10/18 06:00 [entrez]
PHST- 2016/10/18 06:00 [pubmed]
PHST- 2016/10/18 06:01 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2016.00435 [doi]
PST - epublish
SO  - Front Neurosci. 2016 Sep 30;10:435. doi: 10.3389/fnins.2016.00435. eCollection 
      2016.