GluT-1) after transient retinal ischemia

S63

406

REMARKABLE

INCREASE IN GLUTAMATE-ASPARTATE TkWWORTER

TRANSIENT REXINAL ISCHECMIA.YASUMASA TOHYAM&* lDeDt.ol..

(GLAST/GluT-1) AFIER

OTORIl, 2, SHOICHI SHIMADA*, AND MASAYA

Osaka Univ. Medical School. Osaka. 565. Jw

Wept. of Wornv

L Neurosci,

Osaka Univ. Medical School. Q&a. 565. Jaoan. We have demommted the cellular localkticm

of glutamate-~

transporter(GLAST/GluT-1) mRNA in the rat retina

and its induction after transient ischemia by in situhyhridizatiun. GLAST mRNA was expressed in the inner two-thirds of the inner nuclear layer (INL) and in sparse small cells in the inner portion of the ganglion cell layer (GCL) of the adult rat retina. GLAST mRNA was also found in about 90 % of cells in the optic nerve head where more than 90 % of cells express glial fibrillary acidic protein (GFAP) mRNA. Moreover, experimental occlusion of the central retinal artery followed by qerfusion

for 48 h resulted in degeneration of neurons and a mkable

These findings suggest that GLAST may be expressed in Milkcells

incmase in GLAST mRNA expression in the INL. and astmcyks in the retina, and may play an important

role in ~legulatiooof extracellular glutamate coocentration especially under ischcmic conditions.

METHYLPHENYLPYRIDIUM ION ENHANCES GLUTAMATE-INDUCED CYTOTOXICI-N AGAINST 407 DOPAMINERGIC NEURONS IN CULTURED RAT MESENCEPHALON. HIDEYUKI SAWADAl. SHUN SHIMOHAMAI, JUN KIMURAl. TAKAO KAWAMURA2. AKINORI kAIKE2 AND YUTAKA TAMURA3, ‘De&. ofNeuro1 (Fllcultv ofMed.& ~kuum. (Facultv of Warm. and Sci.1 Kwto Univ.. 54 Slmumkkawaramachi, Sakvo-ku. Kvato, 603. Jauan. 3Deut. of Neuroharm,Fukuvama Univ. Facultv of Pharm. Sci.). Fukuvama 729-02. Japan. III Parkinson’s disease brains the reduction in mitochondrial activity is thought to play an important role in selective dopaminergic neuronal death. Methylphenylpyridium ieu (MPP+> suppresses mitoehondrial activity and causes neuronal death of depaminergic neurous. Using primary culture ‘of the rat ventral meseneqhalon, we investigated eytocoxicity iudueed by glutamate against dopaminergic and nondcpaminergic neurons with or without the pretreatment with MPP+. Brief exposure to 100 @4 glutamate showed similar cytatoxic ef%cts against bath dopaminergic and nondopaminergic neurcns. In the dopaminergic ne-urm~, MPP+ caused cytctoxicity that was not blocked by co-administraticn of MK-80 1. After pre&atm& with small doses of MPP+ that itself did not significantly reduce tbe number of surviving dopaminergic neurons, sub-lethal noses of glutamate caused severe cell damage restricted to dopaminergic neurons, suggesting that MPP+ enhances the glutamate-induced cytotoxicity only against dopaminergic neurons.

408 H I ROF u

PROTECTIVE EFFECTS OF IBUDILAST ON GLUTAMATE NEUROTOXICITY IN CULTURED 1 12 1.2 HOPPOCAMPAL NEURONS. YASU~.. Nn. KOJI TSUJI ,. 1 1.3 Departments of ‘Phvsioloev. ‘Orthpaedic Sureerv and MI MIYAZAKI AND KIY OS HI KATAOKA. . . . and Resusntoloev. Universitv. SCIIQQIof Me&me. Shleenobu. 791-02. w

The effect of ibudilast, which is a drug clinically used for improvement of cerebral circulation, on glutamate neurotoxicity was examined in cultured neurons from rat hippocampus. The extent of neuronal damage induced by the exposure to 250 ,uM glutamate for Smin was estimated by the activity of lactate dehydrogenase (LDH) released from degenerated neurons to the Ibudilast showed no cytotoxicity below the concentration of 43 PM The medium during 24 h post-exposure incubation. extent of LDH-release enhanced by the glutamate exposure decreased to 60% of the control level when 43 PM tbudilast was The protective effect was observed in a dose-dependent added into the preincubation-, exposure-, and postexposure-media. Among the three application periods, the postexposure application was most effective for the protection from manner. neurotoxicity.