Impaired expression of excitatory amino acid transporter 2 (EAAT2) and glutamate homeostasis in canine necrotizing meningoencephalitis.
To clarify the involvement of excitatory and inhibitory amino acids in canine necrotizing meningoencephalitis (NME), glutamate, aspartate, taurine and gamma-aminobutylic acid (GABA) were determined in the cerebrospinal fluids (CSF) from eight NME cases and ten healthy controls. NME dogs exhibited significantly higher concentrations of glutamate and aspartate than those in controls (p<0.001 and p<0.001, respectively), while there was no difference in taurine or GABA between the two groups. When fetal canine astrocytes were cultured for 24 hr in the presence of NME-CSF, supernatant concentrations of glutamate, aspartate and taurine were significantly elevated. Simultaneously, expression of excitatory amino acid transporter 2 (EAAT2) mRNA was significantly reduced in the astrocytes without change in EAAT1 mRNA. Hence, reduced expression of EAAT2 and impaired glutamate homeostasis may contribute to the pathogenesis of NME.
Pham
Ngoc-Thi
NT
Laboratory of Veterinary Clinical Pathobiology, Department of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Matsuki
Naoaki
N
Shibuya
Masahiro
M
Tamahara
Satoshi
S
Ono
Kenichiro
K
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism; D004283:Dog Diseases / Q000134:cerebrospinal fluid / Q000378:metabolism*; D004285:Dogs; D027341:Excitatory Amino Acid Transporter 1 / Q000096:biosynthesis / Q000235:genetics; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D004684:Leukoencephalitis, Acute Hemorrhagic / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000662:veterinary*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D013654:Taurine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013654:Taurine; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid