PMID- 17663144
OWN - NLM
STAT- MEDLINE
DCOM- 20070914
LR  - 20131121
IS  - 1881-6096 (Print)
IS  - 1881-6096 (Linking)
VI  - 59
IP  - 7
DP  - 2007 Jul
TI  - [Disruption of amino acid metabolism in astrocyte and neurological 
      disorders--possible implication of abnormal glia-neuron network in 
      homocystineuria].
PG  - 731-7
AB  - CBS is a vitamin B6-dependent transsulfuration enzyme needed to synthesize 
      cysteine from methionine, catalyzing the condensation of serine with homocysteine 
      to form cystathionine. A deficiency of CBS causes homocystinuria (MIM 236200), 
      one of the most prevalent inborn errors, characterized by mental retardation, 
      seizures, psychiatric disturbances, skeletal abnormalities and vascular 
      disorders. Patients with CBS deficiency exhibit a major biochemical abnormality, 
      hyperhomocysteinemia (HHcy), a condition associated with highly elevated plasma 
      homocysteine levels. HHcy is recognized as a risk factor for several neurological 
      diseases, such as cognitive impairment, dementia and Alzheimer's disease. 
      Although the link between CBS deficiency and homocystinuria was first described 
      over 40 years ago and mental retardation was the first clinical feature of the 
      disease to be classified, very little is known about the role of CBS in the CNS. 
      Here we show the regional and cellular distribution of CBS in the adult and 
      developing mouse brain. In the adult mouse brain, CBS was expressed ubiquitously, 
      but most intensely in the cerebellar molecular layer and hippocampal dentate 
      gyrus. Immunohistochemical analysis revealed that CBS is preferentially expressed 
      in cerebellar Bergmann glia and in astrocytes throughout the brain. At early 
      developmental stages, CBS was expressed in neuroepithelial cells in the 
      ventricular zone, but its expression changed to radial glial cells and then to 
      astrocytes during the late embryonic and neonatal periods. Moreover, CBS was 
      significantly accumulated in reactive astrocytes in the hippocampus after kainic 
      acid-induced seizures, and cerebellar morphological abnormalities were observed 
      in CBS-deficient mice. These results support the role of CBS in the development 
      and maintenance of the CNS, and suggest that radial glia/astrocyte dysfunction 
      might be involved in the complex neuropathological features associated with 
      abnormal homocysteine metabolism.
FAU - Enokido, Yasushi
AU  - Enokido Y
AD  - Department of Neuropathology, Medical Research Institute, Tokyo Medical and 
      Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
LA  - jpn
PT  - English Abstract
PT  - Journal Article
PT  - Review
PL  - Japan
TA  - Brain Nerve
JT  - Brain and nerve = Shinkei kenkyu no shinpo
JID - 101299709
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Animals
MH  - Astrocytes/*physiology
MH  - Brain/growth & development
MH  - *Cell Communication
MH  - Cystathionine beta-Synthase/deficiency/genetics/physiology
MH  - DNA Damage
MH  - Homocysteine/metabolism
MH  - Homocystinuria/*etiology
MH  - Humans
MH  - Mental Disorders/etiology
MH  - Mice
MH  - Nervous System Diseases/etiology
MH  - Neurons/*physiology
RF  - 34
EDAT- 2007/08/01 09:00
MHDA- 2007/09/15 09:00
CRDT- 2007/08/01 09:00
PHST- 2007/08/01 09:00 [pubmed]
PHST- 2007/09/15 09:00 [medline]
PHST- 2007/08/01 09:00 [entrez]
PST - ppublish
SO  - Brain Nerve. 2007 Jul;59(7):731-7.