title: Dietary restriction affects striatal glutamate in the MPTP-induced mouse model of nigrostriatal degeneration.
abstract: One month following subchronic treatment with the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg/kg/d x 7 days), there is a decrease in the extracellular level of striatal glutamate. It has been reported that following dietary restriction (DR) (fed on alternate days) of C57BL/6 mice, MPTP administration resulted in a reduction in the loss of tyrosine hydroxylase-positive neurons within the substantia nigra pars compacta (SN-PC) compared to the ad libitum (AL)-fed MPTP-treated mice. However, there have been no reports of whether the MPTP-induced alterations in brain neurochemistry or morphology can be similarly attenuated by DR if initiated after administration of the toxin. In the MPTP/AL group there is a decrease in the extracellular level of striatal glutamate compared to the Vehicle/AL group. However, 21 days of DR starting 1 day after the last subchronic dose of MPTP results in a reversal in the extracellular level of striatal glutamate compared to the MPTP/AL group. DR alone resulted in a decrease in extracellular striatal glutamate. There was no change in the relative density of the glutamate transporter, GLT-1, within the striatum or SN-PC between any of the groups, suggesting that the alterations in striatal extracellular glutamate were not due to a change in this specific transporter. There was an increase in the density of nerve terminal glutamate immunolabeling in the MPTP/AL and MPTP/DR groups compared to the Vehicle/AL group. There was a similar decrease in the relative density of tyrosine hydroxylase immunolabeling within the striatum and the SN-PC in both the MPTP/AL and MPTP/DR groups compared to the Vehicle/AL group. Since a decrease in the activity of the corticostriatal glutamate pathway has been reported in both Parkinson's disease and in animal models of nigrostriatal loss, these data suggest that DR initiated after the partial loss of striatal dopamine appears to reverse the decrease in striatal glutamate.
authors.affiliation: Research Services, Neurocytology Lab, V.A. Medical Center, Portland, Oregon 97239, USA.
authors.forename: Haley K
authors.initials: HK
authors.lastname: Holmer
authors.forename: Modjgan
authors.initials: M
authors.lastname: Keyghobadi
authors.forename: Cynthia
authors.initials: C
authors.lastname: Moore
authors.forename: Rachelle A
authors.initials: RA
authors.lastname: Menashe
authors.forename: Charles K
authors.initials: CK
authors.lastname: Meshul
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D031204:Caloric Restriction; D003342:Corpus Striatum / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D004298:Dopamine / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D027342:Excitatory Amino Acid Transporter 2 / Q000187:drug effects / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism; D005508:Food Deprivation / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D046529:Microscopy, Electron, Transmission; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013378:Substantia Nigra / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine