Mechanisms of excitotoxic neuronal death

Thursday. Sep 24, 1992 La Palms/B

X ICER Abstracts

PHYSIOLOGY/ PHARMACOLOGY

CODE. PP.8

SEPTEMBER

MECNANISMS RETINAL NEUROTRANSMITTERS NEuRoToxlcITY

CH

AND

JOSE SAHEL

NUMBER

TlME

PRESENTATION

1

3:oo

Mecha ‘sms of Excitotoxic S. Ro:hlman (USA)

Neuronal

3:25

Total C&rum Lacalization in Rat w Durin a lsch emia or Glutamate Toxicity M.S. Burns. CM. Panauoni and G.L Baker (USA)

3

3:50

] M. Wcber, E Kerrand. Dreyfus and J. Sahel

5

4:15

4:3s

There is now convincing evidence that glutamate (Glu) and other excitatory amino acids may play a role in the neuronal death that is seen in a variety of common diseases. such as These include acute conditions, stroke and hypoglycemia, as well as some chronic illnesses like Huntington's Disease. It is, therefore, important to try to understand the mechanism(s) by which Glu kills neurons.

Death

N. Bonaventure. (France)

NM D -in of Adult Rat: A model System Pharmacolc&al Studia R. Siliprandi (Italy)

OF WCITOTOXIC NEURONALDEATH

Departmnts of Neurology and Anatomy C Neurobiology, Washington University School of Medicine, St. Louis, Missouh, USA

(FRANCE)

2

4

611

1

24flHURSDAY

Cultured neurons exposed to toxic concentrations of Glu swell dramatically, but this is not always associated with irreversible injury. More damaging than the swelling is the entry of calcium, which also elevates the free intracellular calcium concentration. The correlation between calcium concentration and neuronal death is imperfect, however, because there are circumstances when calcium concentration climbs quite high with little neuronal death. We believe that actual calcium entry from the extracellular space is crucial for cell damage. While Glu neurotoxicity is largely attenuated by specific blockers of the N-methyl-Daspartate (NWA) receptor, we have recently found that drugs which eliminate fast Glu desensitization can dramatically increase Glu toxicity.

M.

for in Vivp

Melatonin Biosvnthesis in Chick Retid Photoreceotor Cells: Evidence for a Rod Pathwav -> Dooamine -> Cone Reg&uuty Mechanrsm P.M. luvonc. M. Taylor. J. Zawilska and K.B. Thorna< (USA)

2

TOTAL CALCIUM LOCALIZATION IN RAT ISCHEMIA OR GLUTAMATE EXCITOTOXICITY Burns. M.S.. Panatto i. C.M.. Baker. G.lk, Department

RETINAS

DURING

of Ophthnahnology,University of California, Davis,USA

Do total calcium levels increase in retinal cells damaged by conditions of glutamate toxicity or lack of oxygen in vitro? Is calcium increase localized to particular cells? Rat retinas were incubated in vitro in modified Ames’ medium under conditions of 95% N&S% CO, or 5 mM glutamate. Electrolyte levels were monitored by atomic absorption spectrometry and localization of calcium was studied with Secondary Ion Mass Spectrometty, using the stable isotope, 42Ca, to monitor calcium inflw. Total calcium levels increased in the incubated retinas as measured with atomic absorption spectrometry, and were apparent as early as 30 minutes of incubation. There was no specific localization in a particular cell layer as measured by Secondary Ion Mass Spectrometry. The intlux of 42-Ca, the stable isotope, into the retina was quite rapid (approximately 75% within 30 minutes)

as it exchanged

for the normally

abundant

40-C&

There

is also a

non-exchangeable pool of 40-Ca which persists in the retina up to 6 hrs incubation. Thus the histological picture of inner retinal swelling in ischemia and glutamate excitotoxicity calcium in this layer.

Supported

does

not correlate

with

a specific

increase

in part by a grant from the Office of Naval Research.

613

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