PMID- 12718448
OWN - NLM
STAT- MEDLINE
DCOM- 20030708
LR  - 20190823
IS  - 0364-3190 (Print)
IS  - 0364-3190 (Linking)
VI  - 28
IP  - 6
DP  - 2003 Jun
TI  - Chronic hypoxia in development selectively alters the activities of key enzymes 
      of glucose oxidative metabolism in brain regions.
PG  - 933-40
AB  - The immature brain is more resistant to hypoxia/ischemia than the mature brain. 
      Although chronic hypoxia can induce adaptive-changes on the developing brain, the 
      mechanisms underlying such adaptive changes are poorly understood. To further 
      elucidate some of the adaptive changes during postnatal hypoxia, we determined 
      the activities of four enzymes of glucose oxidative metabolism in eight brain 
      regions of hypoxic and normoxic rats. Litters of Sprague-Dawley rats were put 
      into the hypoxic chamber (oxygen level maintained at 9.5%) with their dams 
      starting on day 3 postnatal (P3). Age-matched normoxic rats were use as control 
      animals. In P10 hypoxic rats, lactate dehydrogenase (LDH) activity in cerebral 
      cortex, striatum, olfactory bulb, hippocampus, hypothalamus, pons and medulla, 
      and cerebellum was significantly increased (by 100%-370%) compared to those in 
      P10 normoxic rats. In P10 hypoxic rats, hexokinase (HK) activity in hypothalamus, 
      hippocampus, olfactory bulb, midbrain, and cerebral cortex was significantly 
      decreased (by 15%-30%). Neither alpha-ketoglutarate dehydrogenase complex (KGDHC, 
      which is believed to have an important role in the regulation of the 
      tricarboxylic acid [TCA] cycle flux) nor citrate synthase (CS) activity was 
      significantly decreased in the eight regions of P10 hypoxic rats compared to 
      those in P10 normoxic rats. In P30 hypoxic rats, LDH activity was only increased 
      in striatum (by 19%), whereas HK activity was only significantly decreased (by 
      30%) in this region. However, KGDHC activity was significantly decreased in 
      olfactory bulb, hippocampus, hypothalamus, cerebral cortex, and cerebellum (by 
      20%-40%) in P30 hypoxic rats compared to those in P30 normoxic rats. Similarly, 
      CS activity was decreased, but only in olfactory bulb, hypothalamus, and midbrain 
      (by 9%-21%) in P30 hypoxic rats. Our results suggest that at least some of the 
      mechanisms underlying the hypoxia-induced changes in activities of glycolytic 
      enzymes implicate the upregulation of HIF-1. Moreover, our observation that 
      chronic postnatal hypoxia induces differential effects on brain glycolytic and 
      TCA cycle enzymes may have pathophysiological implications (e.g., decreased in 
      energy metabolism) in childhood diseases (e.g., sudden infant death syndrome) in 
      which hypoxia plays a role.
FAU - Lai, James C K
AU  - Lai JC
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Idaho State 
      University, Pocatello, Idaho 83209-8334, USA. lai@otc.isu.edu
FAU - White, Brenda K
AU  - White BK
FAU - Buerstatte, Charles R
AU  - Buerstatte CR
FAU - Haddad, Gabriel G
AU  - Haddad GG
FAU - Novotny, Edward J Jr
AU  - Novotny EJ Jr
FAU - Behar, Kevin L
AU  - Behar KL
LA  - eng
GR  - P01 HD32573/HD/NICHD NIH HHS/United States
GR  - R01 NS34813/NS/NINDS NIH HHS/United States
GR  - P01 HD032573/HD/NICHD NIH HHS/United States
GR  - R01 NS034813/NS/NINDS NIH HHS/United States
GR  - P20 RR16454/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 1.2.4.2 (Ketoglutarate Dehydrogenase Complex)
RN  - EC 2.3.3.1 (Citrate (si)-Synthase)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Aging
MH  - Animals
MH  - Body Weight
MH  - Brain/*enzymology/growth & development
MH  - Citrate (si)-Synthase/*metabolism
MH  - Glucose/metabolism
MH  - Hexokinase/*metabolism
MH  - Hypoxia, Brain/*enzymology
MH  - Ketoglutarate Dehydrogenase Complex/*metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Organ Specificity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reference Values
EDAT- 2003/04/30 05:00
MHDA- 2003/07/09 05:00
CRDT- 2003/04/30 05:00
PHST- 2003/04/30 05:00 [pubmed]
PHST- 2003/07/09 05:00 [medline]
PHST- 2003/04/30 05:00 [entrez]
AID - 10.1023/a:1023235712524 [doi]
PST - ppublish
SO  - Neurochem Res. 2003 Jun;28(6):933-40. doi: 10.1023/a:1023235712524.