PMID- 23228723
OWN - NLM
STAT- MEDLINE
DCOM- 20130722
LR  - 20211021
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1495
DP  - 2013 Feb 7
TI  - Early life nutrient restriction impairs blood-brain metabolic profile and 
      neurobehavior predisposing to Alzheimer's disease with aging.
PG  - 61-75
LID - S0006-8993(12)01844-6 [pii]
LID - 10.1016/j.brainres.2012.11.050 [doi]
AB  - Prenatal nutrient restriction (NR) culminating in intra-uterine growth 
      restriction (IUGR) with postnatal catch up growth leads to diabesity. In 
      contrast, postnatal NR with growth restriction (PNGR) superimposed on IUGR (IPGR) 
      protects young and aging adults from this phenotype. We hypothesized that 
      PNGR/IPGR will compromise the blood-brain metabolic profile impairing 
      neurobehavior and predisposing to Alzheimer's disease (AD). NR (50%) in late 
      gestation followed by cross-fostering of rat pups to either ad lib fed (CON) or 
      NR (50%) lactating mothers generated CON, IUGR, PNGR and IPGR male (M) and female 
      (F) offspring that were examined through the life span. In PNGR/IPGR plasma/CSF 
      glucose and lactate decreased while ketones increased in (M) and (F) (PN21, 
      PN50). In addition increased brain glucose transporters, Glut1 & Glut3, greater 
      brain derived neurotrophic factor (BDNF), reduced Glut4, with unchanged serotonin 
      transporter concentrations were noted in (F) (PN50-60). While (F) displayed more 
      hyperactivity, both (F) and (M) exhibited anxiety although socially and 
      cognitively unimpaired (PN25-28&50). Aging (15-17 m) (F) not (M), expressed low 
      plasma insulin, reduced brain IRS-2, pAkt, and pGSK-3beta(Ser9), unchanged pPDK1, 
      pTau or lipoprotein receptor related protein 1 (LRP1), higher glial fibrillary 
      acidic protein (GFAP) and spinophilin but a 10-fold increased amyloid-beta42. We 
      conclude that therapeutically superimposing PNGR on IUGR (IPGR) should be 
      carefully weighed in light of unintended consequences related to perturbed 
      neurobehavior and potential predilection for AD.
CI  - Copyright (c) 2012 Elsevier B.V. All rights reserved.
FAU - Tomi, Masatoshi
AU  - Tomi M
AD  - Department of Pediatrics, Division of Neonatology and Developmental Biology, 
      Neonatal Research Center, David Geffen School of Medicine UCLA, Los Angeles, CA 
      90095-1752, USA.
FAU - Zhao, Yuanzi
AU  - Zhao Y
FAU - Thamotharan, Shanthie
AU  - Thamotharan S
FAU - Shin, Bo-Chul
AU  - Shin BC
FAU - Devaskar, Sherin U
AU  - Devaskar SU
LA  - eng
GR  - R01 HD041230/HD/NICHD NIH HHS/United States
GR  - R01 HD025024/HD/NICHD NIH HHS/United States
GR  - HD 25024/HD/NICHD NIH HHS/United States
GR  - HD 33997/HD/NICHD NIH HHS/United States
GR  - R01 HD033997/HD/NICHD NIH HHS/United States
GR  - HD 41230/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121207
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
SB  - IM
MH  - Aging/metabolism
MH  - Alzheimer Disease/*etiology/metabolism/physiopathology
MH  - Animals
MH  - Anxiety
MH  - Brain/*metabolism
MH  - Caloric Restriction/*adverse effects
MH  - Disease Models, Animal
MH  - Female
MH  - Fetal Growth Retardation/metabolism/*physiopathology
MH  - Hyperkinesis/etiology
MH  - Male
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/metabolism/*physiopathology
MH  - Rats
PMC - PMC4174601
MID - NIHMS427702
EDAT- 2012/12/12 06:00
MHDA- 2013/07/23 06:00
PMCR- 2014/09/25
CRDT- 2012/12/12 06:00
PHST- 2012/03/23 00:00 [received]
PHST- 2012/11/05 00:00 [revised]
PHST- 2012/11/29 00:00 [accepted]
PHST- 2012/12/12 06:00 [entrez]
PHST- 2012/12/12 06:00 [pubmed]
PHST- 2013/07/23 06:00 [medline]
PHST- 2014/09/25 00:00 [pmc-release]
AID - S0006-8993(12)01844-6 [pii]
AID - 10.1016/j.brainres.2012.11.050 [doi]
PST - ppublish
SO  - Brain Res. 2013 Feb 7;1495:61-75. doi: 10.1016/j.brainres.2012.11.050. Epub 2012 
      Dec 7.