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Accumulation of N ‐Acetyl‐L‐Aspartate in the Brain of the Tremor Rat, a Mutant Exhibiting Absence‐Like Seizure and Spongiform Degeneration in the Central Nervous System
Author(s) -
Kitada Kazuhiro,
Akimitsu Tomohide,
Shigematsu Yosuke,
Kondo Akira,
Maihara Toshiro,
Yokoi Norihide,
Kuramoto Takashi,
Sasa Masashi,
Serikawa Tadao
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0742512.x
Subject(s) - neurodegeneration , mutant , central nervous system , neuroscience , biology , hippocampal formation , medicine , gene , biochemistry , disease
The tremor rat is a mutant that exhibits absence‐like seizure and spongiform degeneration in the CNS. By positional cloning, a genomic deletion was found within the critical region in which the aspartoacylase gene is located. Accordingly, no aspartoacylase expression was detected in any of the tissues examined, and abnormal accumulation of N ‐acetyl‐L‐aspartate (NAA) was shown in the mutant brain, in correlation with the severity of the vacuole formation. Therefore, the tremor rat may be regarded as a suitable animal model of human Canavan disease, characterized by spongy leukodystrophy that is caused by aspartoacylase deficiency. Interestingly, direct injection of NAA into normal rat cerebroventricle induced 4‐ to 10‐Hz polyspikes or spikewave‐like complexes in cortical and hippocampal EEG, concomitantly with behavior characterized by sudden immobility and staring. These results suggested that accumulated NAA in the CNS would induce neuroexcitation and neurodegeneration directly or indirectly.