Neurochemistry in shiverer mouse depicted on MR spectroscopy.
OBJECTIVE
To evaluate the neurochemical changes associated with hypomyelination, especially to clarify whether increased total N-acetylaspartate (tNAA) with decreased choline (Cho) observed in the thalamus of msd mice with the plp1 mutation is a common finding for hypomyelinating disorders.


METHODS
We performed magnetic resonance imaging (MRI) and proton MR spectroscopy ((1) H-MRS) of the thalamus and cortex of postnatal 12-week shiverer mice devoid of myelin basic protein (mbp), heterozygous and wild-type mice with a 7.0T magnet. Luxol Fast Blue staining and immunohistochemical analysis with anti-Mbp, Gfap, Olig2, and NeuN antibodies were also performed.


RESULTS
In the thalamus, decreased Cho and normal tNAA were observed in shiverer mice. In the cortex, tNAA, Cho, and glutamate were decreased in shiverer mice. Histological and immunohistochemical analysis of shiverer mice brains revealed hypomyelination in the thalamus, white matter, and cortex; astrogliosis and an increased number of total oligodendrocytes in the white matter; and a decreased number of neurons in the cortex.


CONCLUSIONS
The reduction of Cho on (1) H-MRS might be a common marker for hypomyelinating disorders. A normal tNAA level in the thalamus of shiverer mice might be explained by the presence of mature oligodendrocytes, which enable neuron-to-oligodendrocyte NAA transport or NAA catabolism.
Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan; Department of Pediatrics, Kameda Medical Center, Kamogawa, Japan; Department of Radiology, Toho University Sakura Medical Center, Sakura, Japan.
Jun-ichi
J
Takanashi
Nobuhiro
N
Nitta
Nobuaki
N
Iwasaki
Shigeyoshi
S
Saito
Ryuta
R
Tanaka
A James
AJ
Barkovich
Ichio
I
Aoki
D026922:Amino Acid Transport Systems, Acidic / Q000172:deficiency* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D017920:Antiporters / Q000172:deficiency* / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D002794:Choline / Q000378:metabolism*; D004195:Disease Models, Animal; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008813:Mice, Inbred ICR; D008818:Mice, Neurologic Mutants; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000473:pathology; D004676:Myelin Basic Protein / Q000378:metabolism; D009448:Neurochemistry / Q000379:methods; D011596:Psychomotor Disorders / Q000378:metabolism* / Q000473:pathology; D013788:Thalamus / Q000378:metabolism / Q000473:pathology; D066127:White Matter / Q000378:metabolism / Q000473:pathology
D026922:Amino Acid Transport Systems, Acidic; D017920:Antiporters; D004676:Myelin Basic Protein; D001224:Aspartic Acid; C000179:N-acetylaspartate; D002794:Choline
N-acetylaspartate; choline; hypomyelination; magnetic resonance spectroscopy; myelin basic protein; shiverer mouse