Neuroprotection by taurine in ethanol-induced apoptosis in the developing cerebellum.
BACKGROUND
Acute ethanol administration leads to massive apoptotic neurodegeneration in the developing central nervous system. We studied whether taurine is neuroprotective in ethanol-induced apoptosis in the mouse cerebellum during the postnatal period.


METHODS
The mice were divided into three groups: ethanol-treated, ethanol+taurine-treated and controls. Ethanol (20% solution) was administered subcutaneously at a total dose of 5 g/kg (2.5 g/kg at time 1 h and 2.5 g/kg at 3 h) to the ethanol and ethanol+taurine groups. The ethanol+taurine group also received two injections of taurine (1 g/kg each, at time zero and at 4 h). To estimate apoptosis, immunostaining for activated caspase-3 and TUNEL staining were made in the mid-sagittal sections containing lobules I-X of the cerebellar vermis at 12 or 8 hours after the first taurine injection. Changes in the blood taurine level were monitored at each hour by reverse-phase high-performance liquid chromatography (HPLC).


RESULTS
Ethanol administration induced apoptosis of Purkinje cells on P4 in all cerebellar lobules, most extensively in lobules IX and X, and on P7 increased the number of activated caspase-3-immunoreactive and TUNEL-positive cells in the internal layer of the cerebellum. Administration of taurine significantly decreased the number of activated caspase-3-immunoreactive and TUNEL-positive cells in the internal layer of the cerebellum on P7, but had no effect on Purkinje cells in P4 mice. The high initial taurine concentration in blood of the ethanol+taurine group diminished dramatically during the experiment, not being different at 13 h from that in the controls.


CONCLUSIONS
We conclude that the neuroprotective action of taurine is not straightforward and seems to be different in different types of neurons and/or requires prolonged maintenance of the high taurine concentration in blood plasma.
Taranukhin
Andrey G
AG
Brain Research Center, University of Tampere Medical School, Tampere, Finland. andrey.taranukhin@uta.fi
Taranukhina
Elena Y
EY
Saransaari
Pirjo
P
Podkletnova
Irina M
IM
Pelto-Huikko
Markku
M
Oja
Simo S
SS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced*; D018696:Neuroprotective Agents / Q000097:blood / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D013654:Taurine / Q000097:blood / Q000494:pharmacology*
D002492:Central Nervous System Depressants; D018696:Neuroprotective Agents; D013654:Taurine; D000431:Ethanol; D053148:Caspase 3
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