Neuroprotective effect of small heat shock protein, Hsp27, after acute and chronic alcohol administration.
Alcohol induces degeneration of neurons and inhibits neurogenesis in the brain. Small heat shock proteins are able to protect neurons in cerebral ischemia and oxidative stress. In this study, we investigated the neuroprotective effect of small heat shock protein, Hsp27, after acute and chronic ethanol administrations using transgenic mice overexpressing the human Hsp27 protein. Transgenic mice and wild-type littermates were injected with 2 g/kg ethanol intraperitoneally, and then motor coordination and muscle strength were analyzed using different behavioral tests, such as footprint analysis, balance beam, and inverted screen tests. Ethanol-injected transgenic mice showed similar footprints to control saline-injected mice, did not fall of the beam, and were able to climb to the top of the inverted screen, while wild-type mice showed ataxia and incoordination after ethanol injection. The effect of Hsp27 on chronic ethanol consumption was also investigated. Drinking water of mice was replaced by a 20% ethanol solution for 5 weeks, and then brain sections were stained with Fluoro Jade C staining. We found significantly lesser amount of degenerating neurons in the brain of ethanol-drinking transgenic mice compared to wild-type mice. We conclude that Hsp27 can protect neurons against the acute and chronic toxic effects of ethanol.
Toth
Melinda Erzsebet
ME
Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, P.O. Box 521, 6701, Szeged, Hungary.
Gonda
Szilvia
S
Vigh
Laszlo
L
Santha
Miklos
M
D000428:Alcohol Drinking; D000818:Animals; D001522:Behavior, Animal; D000431:Ethanol / Q000633:toxicity*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism*
D055551:HSP27 Heat-Shock Proteins; D018696:Neuroprotective Agents; D000431:Ethanol
Biochim Biophys Acta. 2005 Dec 30;1720(1-2):92-8
16472556
Cell Physiol Biochem. 2006;17(3-4):97-110
16543726
Prog Neurobiol. 1998 Nov;56(4):385-431
9775400
Psychopharmacology (Berl). 1984;83(3):272-6
6433390
Psychopharmacology (Berl). 1977 Apr 29;52(2):201-6
407605
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13504-9
12368478
Mol Cell Biol. 1988 Dec;8(12):5059-71
3072471
J Biol Chem. 2000 Mar 3;275(9):6664-72
10692476
J Neurochem. 2002 Apr;81(2):355-64
12064483
Brain Res. 2005 Feb 21;1035(1):24-31
15713273
J Biol Chem. 2003 May 30;278(22):19956-65
12639970
Proc Natl Acad Sci U S A. 2007 May 8;104(19):7945-50
17470815
J Biol Chem. 1996 Jul 12;271(28):16510-4
8663291
FEBS J. 2008 Mar;275(6):1296-308
18279381
J Appl Physiol (1985). 2003 Oct;95(4):1338-51
12704090
Arch Biochem Biophys. 2005 Apr 15;436(2):346-54
15797247
Cell Stress Chaperones. 2009 Jan;14(1):105-11
18663603
Cell Mol Life Sci. 2007 Feb;64(3):294-306
17187175
J Biol Chem. 2007 Sep 21;282(38):28149-56
17664274
FEBS J. 2005 Dec;272(23):6077-86
16302971
Circ Res. 2003 Jun 27;92(12):e87-100
12775586
Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2192-7
9122170
Neuroreport. 1999 Jan 18;10(1):93-6
10094140
FEBS Lett. 1992 Nov 30;313(3):307-13
1332886
Dig Dis Sci. 2008 Mar;53(3):606-13
17763949
J Biol Chem. 1999 Feb 19;274(8):5061-9
9988753
Nat Rev Neurosci. 2005 Jan;6(1):11-22
15611723
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3098-103
11248038
Biochim Biophys Acta. 2008 Jul-Aug;1778(7-8):1653-64
18371297