Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency

• Published in: Neuroscience letters 2004-03, Vol.358 (1), p.29-32
• Main Authors: Surendran, S, Ezell, E.L, Quast, M.J, Wei, J, Tyring, S.K, Michals-Matalon, K, Matalon, R
• Format: Article
• Language: English
• Subjects: Alanine aminotransferase; Aldehyde Oxidoreductases - deficiency; Aldehyde Oxidoreductases - genetics; Animals; Biological and medical sciences; Canavan disease; Canavan Disease - enzymology; Canavan Disease - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Fundamental and applied biological sciences. Psychology; Glutamate dehydrogenase; Intellectual Disability - enzymology; Intellectual Disability - genetics; Medical sciences; Mice; Mice, Knockout; Muscle Hypotonia - enzymology; Muscle Hypotonia - genetics; Neurology; Succinate; Succinate semialdehyde dehydrogenase; Vertebrates: nervous system and sense organs; α-Ketoglutarate dehydrogenase complex
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2003.12.105

Canavan disease (CD) is an autosomal recessive disorder caused by aspartoacylase deficiency leading to accumulation of N-acetylaspartic acid and spongy degeneration of the brain. The mouse model for CD showed low levels of glutamate and γ-aminobutyric acid (GABA) in the brain. Whether the low levels of glutamate and GABA observed in the CD mouse brain lead to abnormal production of glutamate-GABA associated enzymes and resulting succinate production is not obvious. While glutamate dehydrogenase and α-ketoglutarate dehydrogenase complex activities are lower in the cerebellum and brain stem of the CD mouse, alanine aminotransferase and succinate semialdehyde dehydrogenase (SSADH) activities and succinate level are similar to the levels observed in the wild type. Deficiency of SSADH has been suggested to be associated with mental retardation and hypotonia, similar to the clinical features of CD. The normal SSADH activity in the CD mouse brain suggests that mental retardation and hypotonia seen in the CD mouse is not due to SSADH activity and if documented also in patients with CD.