PMID- 27640132
OWN - NLM
STAT- MEDLINE
DCOM- 20170627
LR  - 20191210
IS  - 1873-507X (Electronic)
IS  - 0031-9384 (Linking)
VI  - 167
DP  - 2016 Dec 1
TI  - Differential effects of early-life NMDA receptor antagonism on aspartame-impaired 
      insulin tolerance and behavior.
PG  - 209-221
LID - S0031-9384(16)30816-2 [pii]
LID - 10.1016/j.physbeh.2016.09.011 [doi]
AB  - We have previously showed that lifetime exposure to aspartame, commencing in 
      utero via the mother's diet, may impair insulin tolerance and cause behavioral 
      deficits in adulthood via mechanisms which are incompletely understood. The role 
      of the CNS in regulating glucose homeostasis has been highlighted by recent 
      delineation of the gut-brain axis, in which N-methyl-d-aspartic acid receptors 
      (NMDARs) are important in maintaining glucose homeostasis, in addition to 
      regulating certain aspects of behavior. Since the gut-brain axis can be modulated 
      by fetal programming, we hypothesized that early-life NMDAR antagonism may affect 
      aspartame-induced glucose deregulation in adulthood, and may alter the aspartame 
      behavioral phenotype. Accordingly, C57Bl/6J mice were chronically exposed to 
      aspartame commencing in utero, in the presence and absence of maternal 
      administration of the competitive NMDAR antagonist CGP 39551, from conception 
      until weaning. Drug/diet interactions in adulthood glucocentric and behavioral 
      parameters were assessed. Aspartame exposure elevated blood glucose and impaired 
      insulin-induced glucose disposal during an insulin tolerance test, which could be 
      normalized by NMDAR antagonism. The same effects were not observed in control 
      diet mice, suggesting an early-life drug/diet interaction. Behavioral analysis of 
      adult offspring indicated that NMDAR antagonism of control diet mice caused 
      hyperlocomotion and impaired spatial navigation. Conversely hypolocomotion, 
      reduced exploratory activity and increased anxiety-related behavior were apparent 
      in aspartame diet mice with early-life NMDAR antagonism. CONCLUSION: significant 
      drug/diet interactions in glucocentric and behavioral parameters were identified 
      in aspartame-exposed mice with early-life NMDAR antagonism. This suggests a 
      possible involvement of early NMDAR interactions in aspartame-impaired glucose 
      homeostasis and behavioral deficits.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Collison, Kate S
AU  - Collison KS
AD  - Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, PO 
      Box 3354, Riyadh 11211, Saudi Arabia. Electronic address: kate@kfshrc.edu.sa.
FAU - Inglis, Angela
AU  - Inglis A
AD  - Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, PO 
      Box 3354, Riyadh 11211, Saudi Arabia.
FAU - Shibin, Sherin
AU  - Shibin S
AD  - Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, PO 
      Box 3354, Riyadh 11211, Saudi Arabia.
FAU - Andres, Bernard
AU  - Andres B
AD  - Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, PO 
      Box 3354, Riyadh 11211, Saudi Arabia.
FAU - Ubungen, Rosario
AU  - Ubungen R
AD  - Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, PO 
      Box 3354, Riyadh 11211, Saudi Arabia.
FAU - Thiam, Jennifer
AU  - Thiam J
AD  - Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, PO 
      Box 3354, Riyadh 11211, Saudi Arabia.
FAU - Mata, Princess
AU  - Mata P
AD  - Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, PO 
      Box 3354, Riyadh 11211, Saudi Arabia.
FAU - Al-Mohanna, Futwan A
AU  - Al-Mohanna FA
AD  - Department of Cell Biology, King Faisal Specialist Hospital & Research Centre, PO 
      Box 3354, Riyadh 11211, Saudi Arabia.
LA  - eng
PT  - Journal Article
DEP - 20160915
PL  - United States
TA  - Physiol Behav
JT  - Physiology & behavior
JID - 0151504
RN  - 0 (Blood Glucose)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Sweetening Agents)
RN  - 127910-32-1 (CGP 39551)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
RN  - Z0H242BBR1 (Aspartame)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/*analogs & derivatives/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Aspartame/*adverse effects
MH  - Behavior, Animal/*drug effects
MH  - Blood Glucose/drug effects
MH  - Dark Adaptation/drug effects
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Exploratory Behavior/drug effects
MH  - Female
MH  - *Insulin Resistance
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/chemically induced/*physiopathology
MH  - Recognition, Psychology/drug effects
MH  - Statistics, Nonparametric
MH  - Sweetening Agents/*adverse effects
OTO - NOTNLM
OT  - Aspartame
OT  - Behavior
OT  - Gut-brain axis
OT  - Insulin tolerance
OT  - NMDA receptor antagonism
EDAT- 2016/10/25 06:00
MHDA- 2017/06/28 06:00
CRDT- 2016/09/19 06:00
PHST- 2016/04/25 00:00 [received]
PHST- 2016/08/09 00:00 [revised]
PHST- 2016/09/13 00:00 [accepted]
PHST- 2016/10/25 06:00 [pubmed]
PHST- 2017/06/28 06:00 [medline]
PHST- 2016/09/19 06:00 [entrez]
AID - S0031-9384(16)30816-2 [pii]
AID - 10.1016/j.physbeh.2016.09.011 [doi]
PST - ppublish
SO  - Physiol Behav. 2016 Dec 1;167:209-221. doi: 10.1016/j.physbeh.2016.09.011. Epub 
      2016 Sep 15.