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   J Neurochem 2000 Jul;75(1):314-20
   
Beneficial effects of dietary restriction on cerebral cortical synaptic
terminals: preservation of glucose and glutamate transport and mitochondrial
function after exposure to amyloid beta-peptide, iron, and 3-nitropropionic
acid.

    Guo Z, Ersoz A, Butterfield DA, Mattson MP
    
   Sanders-Brown Research Center on Aging. Department of Chemistry and
   Center of Membrane Sciences, University of Kentucky, Lexington,
   Kentucky, USA.
   
   Recent studies have shown that rats and mice maintained on a dietary
   restriction (DR) regimen exhibit increased resistance of neurons to
   excitotoxic, oxidative, and metabolic insults in experimental models
   of Alzheimer's, Parkinson's, and Huntington's diseases and stroke.
   Because synaptic terminals are sites where the neurodegenerative
   process may begin in such neurodegenerative disorders, we determined
   the effects of DR on synaptic homeostasis and vulnerability to
   oxidative and metabolic insults. Basal levels of glucose uptake were
   similar in cerebral cortical synaptosomes from rats maintained on DR
   for 3 months compared with synaptosomes from rats fed ad libitum.
   Exposure of synaptosomes to oxidative insults (amyloid beta-peptide
   and Fe(2+)) and a metabolic insult (the mitochondrial toxin
   3-nitropropionic acid) resulted in decreased levels of glucose uptake.
   Impairment of glucose uptake following oxidative and metabolic insults
   was significantly attenuated in synaptosomes from rats maintained on
   DR. DR was also effective in protecting synaptosomes against oxidative
   and metabolic impairment of glutamate uptake. Loss of mitochondrial
   function caused by oxidative and metabolic insults, as indicated by
   increased levels of reactive oxygen species and decreased
   transmembrane potential, was significantly attenuated in synaptosomes
   from rats maintained on DR. Levels of the stress proteins HSP-70 and
   GRP-78 were increased in synaptosomes from DR rats, consistent with
   previous data suggesting that the neuroprotective mechanism of DR
   involves a "preconditioning" effect. Collectively, our data provide
   the first evidence that DR can alter synaptic homeostasis in a manner
   that enhances the ability of synapses to withstand adversity.
   
   PMID: 10854276, UI: 20312884
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   Arch Neurol 1999 May;56(5):569-74
   
Increased basal ganglia iron levels in Huntington disease.

    Bartzokis G, Cummings J, Perlman S, Hance DB, Mintz J
    
   Department of Psychiatry, University of Arkansas for Medical Sciences,
   Central Arkansas Veterans Healthcare System, Little Rock 72114, USA.
   gbar@ucla.edu
   
   OBJECTIVE: To quantify in vivo brain ferritin iron levels in patients
   with Huntington disease (HD) and normal control subjects. DESIGN AND
   SUBJECTS: A magnetic resonance imaging method that can quantify
   ferritin iron levels with specificity in vivo was employed to study 11
   patients with HD and a matched group of 27 normal controls. Three
   basal ganglia structures (caudate, putamen, and globus pallidus) and 1
   comparison region (frontal lobe white matter) were evaluated. RESULTS:
   Basal ganglia iron levels were significantly increased (P<.002) in
   patients with HD, and this increase occurred early in the disease
   process. This was not a generalized phenomenon, as white matter iron
   levels were lower in patients with HD. CONCLUSIONS: The data suggest
   that increased iron levels may be related to the pattern of
   neurotoxicity observed in HD. Reducing the oxidative stress associated
   with increased iron levels may offer novel ways to delay the rate of
   progression and possibly defer the onset of HD.
   
   PMID: 10328252, UI: 99258804
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