PMID- 19270429
OWN - NLM
STAT- MEDLINE
DCOM- 20090526
LR  - 20190911
IS  - 1347-8613 (Print)
IS  - 1347-8613 (Linking)
VI  - 109
IP  - 3
DP  - 2009 Mar
TI  - Glycine transporter blockade ameliorates motor ataxia in a mouse model of 
      spinocerebellar atrophy.
PG  - 444-8
AB  - Ataxic movement, the common major symptom of spinocerebellar atrophy, has been 
      considered to involve impaired glutamatergic excitatory neurotransmission in the 
      cerebellum. Considering the therapeutic importance of ataxia control, we assessed 
      the effectiveness of increasing the extracellular concentration of glycine by 
      administering it exogenously or via blockade of glycine transporter 1, using its 
      selective inhibitors sarcosine and 
      N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine (NFPS), for 
      amelioration of motor ataxia in a mouse model of spinocerebellar atrophy 
      developing after neonatal treatment with cytosine beta-D-arabinofuranoside. 
      Intracerebroventricular (i.c.v.) injection of sarcosine (3, 10, and 30 microg) 
      and NFPS (0.01 and 0.03 microg) reduced the number of falls without affecting 
      spontaneous motor activity, and therefore the falling index [(number of falls / 
      spontaneous motor activity) x 100], and dose-dependently ameliorated ataxic 
      movements. Similar effects were observed upon i.c.v. injection of D-serine (1 and 
      10 microg), an agonist of the glycine-recognition site of the 
      N-methyl-D-aspartate (NMDA) receptor. However, exogenously injected glycine (1, 
      3, and 10 microg, i.c.v.) only weakly ameliorated the ataxic movements at 3 
      microg. These results suggest the therapeutic relevance of GlyT1 inhibitors for 
      amelioration of motor ataxia in spinocerebellar atrophy by increasing the 
      endogenous concentration of glycine near the glycine-recognition site of the NMDA 
      receptor.
FAU - Tanabe, Mitsuo
AU  - Tanabe M
AD  - Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, 
      Nagoya City University, Japan. mitana@phar.nagoya-cu.ac.jp
FAU - Nakano, Tomoharu
AU  - Nakano T
FAU - Honda, Motoko
AU  - Honda M
FAU - Ono, Hideki
AU  - Ono H
LA  - eng
PT  - Journal Article
DEP - 20090307
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (Glycine Plasma Membrane Transport Proteins)
RN  - 0 
      (N-(3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)-3-(4'-phenylphenoxy)propyl)sarcosine)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 04079A1RDZ (Cytarabine)
RN  - 452VLY9402 (Serine)
RN  - TE7660XO1C (Glycine)
RN  - Z711V88R5F (Sarcosine)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cytarabine
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Glycine/administration & dosage/pharmacology
MH  - Glycine Plasma Membrane Transport Proteins/*antagonists & inhibitors
MH  - Injections, Intraventricular
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Receptors, N-Methyl-D-Aspartate/drug effects/metabolism
MH  - Sarcosine/administration & dosage/*analogs & derivatives/*pharmacology
MH  - Serine/administration & dosage/pharmacology
MH  - Spinocerebellar Ataxias/*drug therapy/physiopathology
EDAT- 2009/03/10 09:00
MHDA- 2009/05/27 09:00
CRDT- 2009/03/10 09:00
PHST- 2009/03/10 09:00 [entrez]
PHST- 2009/03/10 09:00 [pubmed]
PHST- 2009/05/27 09:00 [medline]
AID - JST.JSTAGE/jphs/08329FP [pii]
AID - 10.1254/jphs.08329fp [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2009 Mar;109(3):444-8. doi: 10.1254/jphs.08329fp. Epub 2009 Mar 
      7.