Increased glutamate receptor and transporter expression in the cerebral cortex and striatum of Gcdh-/- mice: Possible implications for the neuropathology of glutaric acidemia type I

Valeska Lizzi Lagranha, Ursula Matte, Talita Giacomet De Carvalho, Bianca Seminotti, Carolina Coffi Pereira, David Koeller, Michael Woontner, Stephen I. Goodman, Diogo Onofre Gomes De Souza, Moacir Wajner

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

We determined mRNA expression of the ionotropic glutamate receptors NMDA (NR1, NR2A and NR2B subunits), AMPA (GluR2 subunit) and kainate (GluR6 subunit), as well as of the glutamate transporters GLAST and GLT1 in cerebral cortex and striatum of wild type (WT) and glutaryl-CoA dehydrogenase deficient (Gchh -/-) mice aged 7, 30 and 60 days. The protein expression levels of some of these membrane proteins were also measured. Overexpression of NR2A and NR2B in striatum and of GluR2 and GluR6 in cerebral cortex was observed in 7-day-old Gcdh-/-. There was also an increase of mRNA expression of all NMDA subunits in cerebral cortex and of NR2A and NR2B in striatum of 30-day-old Gcdh-/- mice. At 60 days of life, all ionotropic receptors were overexpressed in cerebral cortex and striatum of Gcdh-/- mice. Higher expression of GLAST and GLT1 transporters was also verified in cerebral cortex and striatum of Gcdh-/- mice aged 30 and 60 days, whereas at 7 days of life GLAST was overexpressed only in striatum from this mutant mice. Furthermore, high lysine intake induced mRNA overexpression of NR2A, NR2B and GLAST transcripts in striatum, as well as of GluR2 and GluR6 in both striatum and cerebral cortex of Gcdh-/- mice. Finally, we found that the protein expression of NR2A, NR2B, GLT1 and GLAST were significantly greater in cerebral cortex of Gcdh-/- mice, whereas NR2B and GLT1 was similarly enhanced in striatum, implying that these transcripts were translated into their products. These results provide evidence that glutamate receptor and transporter expression is higher in Gcdh-/- mice and that these alterations may be involved in the pathophysiology of GA I and possibly explain, at least in part, the vulnerability of striatum and cerebral cortex to injury in patients affected by GA I.

Original languageEnglish (US)
Article numbere90477
JournalPLoS One
Volume9
Issue number3
DOIs
StatePublished - Mar 4 2014

Fingerprint

neuropathology
Amino Acid Transport System X-AG
cerebral cortex
Glutamate Receptors
Cerebral Cortex
transporters
N-Methylaspartate
Messenger RNA
Glutaryl-CoA Dehydrogenase
mice
Ionotropic Glutamate Receptors
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Kainic Acid
Lysine
Membrane Proteins
Proteins
protein synthesis
Neuropathology
Glutaric Acidemia I
glutamate receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Increased glutamate receptor and transporter expression in the cerebral cortex and striatum of Gcdh-/- mice : Possible implications for the neuropathology of glutaric acidemia type I. / Lagranha, Valeska Lizzi; Matte, Ursula; De Carvalho, Talita Giacomet; Seminotti, Bianca; Pereira, Carolina Coffi; Koeller, David; Woontner, Michael; Goodman, Stephen I.; De Souza, Diogo Onofre Gomes; Wajner, Moacir.

In: PLoS One, Vol. 9, No. 3, e90477, 04.03.2014.

Research output: Contribution to journalArticle

Lagranha, Valeska Lizzi ; Matte, Ursula ; De Carvalho, Talita Giacomet ; Seminotti, Bianca ; Pereira, Carolina Coffi ; Koeller, David ; Woontner, Michael ; Goodman, Stephen I. ; De Souza, Diogo Onofre Gomes ; Wajner, Moacir. / Increased glutamate receptor and transporter expression in the cerebral cortex and striatum of Gcdh-/- mice : Possible implications for the neuropathology of glutaric acidemia type I. In: PLoS One. 2014 ; Vol. 9, No. 3.
@article{369bae45820d4a16a15c90fc262cec30,
title = "Increased glutamate receptor and transporter expression in the cerebral cortex and striatum of Gcdh-/- mice: Possible implications for the neuropathology of glutaric acidemia type I",
abstract = "We determined mRNA expression of the ionotropic glutamate receptors NMDA (NR1, NR2A and NR2B subunits), AMPA (GluR2 subunit) and kainate (GluR6 subunit), as well as of the glutamate transporters GLAST and GLT1 in cerebral cortex and striatum of wild type (WT) and glutaryl-CoA dehydrogenase deficient (Gchh -/-) mice aged 7, 30 and 60 days. The protein expression levels of some of these membrane proteins were also measured. Overexpression of NR2A and NR2B in striatum and of GluR2 and GluR6 in cerebral cortex was observed in 7-day-old Gcdh-/-. There was also an increase of mRNA expression of all NMDA subunits in cerebral cortex and of NR2A and NR2B in striatum of 30-day-old Gcdh-/- mice. At 60 days of life, all ionotropic receptors were overexpressed in cerebral cortex and striatum of Gcdh-/- mice. Higher expression of GLAST and GLT1 transporters was also verified in cerebral cortex and striatum of Gcdh-/- mice aged 30 and 60 days, whereas at 7 days of life GLAST was overexpressed only in striatum from this mutant mice. Furthermore, high lysine intake induced mRNA overexpression of NR2A, NR2B and GLAST transcripts in striatum, as well as of GluR2 and GluR6 in both striatum and cerebral cortex of Gcdh-/- mice. Finally, we found that the protein expression of NR2A, NR2B, GLT1 and GLAST were significantly greater in cerebral cortex of Gcdh-/- mice, whereas NR2B and GLT1 was similarly enhanced in striatum, implying that these transcripts were translated into their products. These results provide evidence that glutamate receptor and transporter expression is higher in Gcdh-/- mice and that these alterations may be involved in the pathophysiology of GA I and possibly explain, at least in part, the vulnerability of striatum and cerebral cortex to injury in patients affected by GA I.",
author = "Lagranha, {Valeska Lizzi} and Ursula Matte and {De Carvalho}, {Talita Giacomet} and Bianca Seminotti and Pereira, {Carolina Coffi} and David Koeller and Michael Woontner and Goodman, {Stephen I.} and {De Souza}, {Diogo Onofre Gomes} and Moacir Wajner",
year = "2014",
month = "3",
day = "4",
doi = "10.1371/journal.pone.0090477",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Increased glutamate receptor and transporter expression in the cerebral cortex and striatum of Gcdh-/- mice

T2 - Possible implications for the neuropathology of glutaric acidemia type I

AU - Lagranha, Valeska Lizzi

AU - Matte, Ursula

AU - De Carvalho, Talita Giacomet

AU - Seminotti, Bianca

AU - Pereira, Carolina Coffi

AU - Koeller, David

AU - Woontner, Michael

AU - Goodman, Stephen I.

AU - De Souza, Diogo Onofre Gomes

AU - Wajner, Moacir

PY - 2014/3/4

Y1 - 2014/3/4

N2 - We determined mRNA expression of the ionotropic glutamate receptors NMDA (NR1, NR2A and NR2B subunits), AMPA (GluR2 subunit) and kainate (GluR6 subunit), as well as of the glutamate transporters GLAST and GLT1 in cerebral cortex and striatum of wild type (WT) and glutaryl-CoA dehydrogenase deficient (Gchh -/-) mice aged 7, 30 and 60 days. The protein expression levels of some of these membrane proteins were also measured. Overexpression of NR2A and NR2B in striatum and of GluR2 and GluR6 in cerebral cortex was observed in 7-day-old Gcdh-/-. There was also an increase of mRNA expression of all NMDA subunits in cerebral cortex and of NR2A and NR2B in striatum of 30-day-old Gcdh-/- mice. At 60 days of life, all ionotropic receptors were overexpressed in cerebral cortex and striatum of Gcdh-/- mice. Higher expression of GLAST and GLT1 transporters was also verified in cerebral cortex and striatum of Gcdh-/- mice aged 30 and 60 days, whereas at 7 days of life GLAST was overexpressed only in striatum from this mutant mice. Furthermore, high lysine intake induced mRNA overexpression of NR2A, NR2B and GLAST transcripts in striatum, as well as of GluR2 and GluR6 in both striatum and cerebral cortex of Gcdh-/- mice. Finally, we found that the protein expression of NR2A, NR2B, GLT1 and GLAST were significantly greater in cerebral cortex of Gcdh-/- mice, whereas NR2B and GLT1 was similarly enhanced in striatum, implying that these transcripts were translated into their products. These results provide evidence that glutamate receptor and transporter expression is higher in Gcdh-/- mice and that these alterations may be involved in the pathophysiology of GA I and possibly explain, at least in part, the vulnerability of striatum and cerebral cortex to injury in patients affected by GA I.

AB - We determined mRNA expression of the ionotropic glutamate receptors NMDA (NR1, NR2A and NR2B subunits), AMPA (GluR2 subunit) and kainate (GluR6 subunit), as well as of the glutamate transporters GLAST and GLT1 in cerebral cortex and striatum of wild type (WT) and glutaryl-CoA dehydrogenase deficient (Gchh -/-) mice aged 7, 30 and 60 days. The protein expression levels of some of these membrane proteins were also measured. Overexpression of NR2A and NR2B in striatum and of GluR2 and GluR6 in cerebral cortex was observed in 7-day-old Gcdh-/-. There was also an increase of mRNA expression of all NMDA subunits in cerebral cortex and of NR2A and NR2B in striatum of 30-day-old Gcdh-/- mice. At 60 days of life, all ionotropic receptors were overexpressed in cerebral cortex and striatum of Gcdh-/- mice. Higher expression of GLAST and GLT1 transporters was also verified in cerebral cortex and striatum of Gcdh-/- mice aged 30 and 60 days, whereas at 7 days of life GLAST was overexpressed only in striatum from this mutant mice. Furthermore, high lysine intake induced mRNA overexpression of NR2A, NR2B and GLAST transcripts in striatum, as well as of GluR2 and GluR6 in both striatum and cerebral cortex of Gcdh-/- mice. Finally, we found that the protein expression of NR2A, NR2B, GLT1 and GLAST were significantly greater in cerebral cortex of Gcdh-/- mice, whereas NR2B and GLT1 was similarly enhanced in striatum, implying that these transcripts were translated into their products. These results provide evidence that glutamate receptor and transporter expression is higher in Gcdh-/- mice and that these alterations may be involved in the pathophysiology of GA I and possibly explain, at least in part, the vulnerability of striatum and cerebral cortex to injury in patients affected by GA I.

UR - http://www.scopus.com/inward/record.url?scp=84897052921&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897052921&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0090477

DO - 10.1371/journal.pone.0090477

M3 - Article

C2 - 24594605

AN - SCOPUS:84897052921

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 3

M1 - e90477

ER -