کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2493598 1556650 2012 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The neurosteroid dehydroepiandrosterone (DHEA) protects the retina from AMPA-induced excitotoxicity: NGF TrkA receptor involvement
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
The neurosteroid dehydroepiandrosterone (DHEA) protects the retina from AMPA-induced excitotoxicity: NGF TrkA receptor involvement
چکیده انگلیسی

The aim of the present study was to investigate the neuroprotective properties of the endogenous neurosteroid dehydroepiandrosterone (DHEA) in an in vivo model of retinal excitotoxicity, and the involvement of Nerve Growth Factor (NGF) in its actions. Adult Sprague–Dawley rats (250–300 g) received intravitreally (RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid hydrobromide (AMPA; 42 nmol/eye) alone or in combination with DHEA (10−8, 10−7, 10−6 M), or PBS (50 mM, control group). To examine the involvement of NGF and its TrkA receptor in the pharmacological effects of DHEA, animals received AMPA and NGF (60 pg/eye) in the absence or presence of a TrkA receptor inhibitor (Calbiochem 648450, 10−6 M) or AMPA, DHEA (10−6 M) and TrkA receptor inhibitor (10−6, 10−5 M). Immunohistochemistry studies [choline acetyltransferase (ChAT), brain nitric oxide synthetase (bNOS), calbindin, and TUNEL] and fluorescence-activated cell sorting (FACS) were used to examine retinal cell loss and protection. TrkA receptor immunoreactivity (-IR) and colocalization studies with relevant markers were also performed. AMPA (42 nmol) treatment resulted in a loss of bNOS, ChAT and calbindin immunoreactivities 24 h after its administration. DHEA, administered intravitreally, protected the retina from excitotoxicity in a dose-dependent manner. This effect was mimicked by NGF, and reversed by the NGF TrkA receptor inhibitor. The TrkA receptor is expressed in ganglion cells of rat retina. TUNEL staining and FACS analysis substantiated the neuroprotective actions of DHEA. These results demonstrate for the first time that the neurosteroid DHEA, administered intravitreally, protects the retina from AMPA excitotoxicity. An NGF TrkA receptor mechanism appears to be involved in this neuroprotection.


► The neurosteroid DHEA provides retinal neuroprotection against AMPA excitotoxicity.
► The NGF TrkA receptor is involved in DHEA's actions.
► DHEA is a promising target for the treatment of the neurodegenerative component of retinal disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 62, Issues 5–6, April 2012, Pages 2106–2117
نویسندگان
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