ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Activation of metabotropic glutamate receptor 5 (mGluR5) has been shown to reduce caspase-dependent apoptosis in primary neuronal cultures induced by staurosporine and etoposide. β-Amyloid (Aβ)-induced neurotoxicity in culture appears to be in part caspase mediated. In the present studies the effects of treatment with an mGluR5 agonist or antagonist on Aβ-induced neuronal apoptosis were examined in rat cortical neuronal cultures. Pretreatment with the selective mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) markedly reduced the number of apoptotic cells after exposure to Aβ (25–35), as well as associated LDH release. Blockade of mGluR5 by the selective antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP) attenuated these effects of CHPG. A similar neuroprotective effect of mGluR5 activation by CHPG was observed in cultures treated with full-length Aβ peptide (1–42). CHPG attenuated Aβ (25–35)-induced cytochrome c release and decreased levels of active caspase-3 protein. CHPG also reduced translocation of apoptosis-inducing factor (AIF) induced by Aβ (25–35). Thus, mGluR5 activation limits the release of mitochondrial proteins associated with induction of both caspase-dependent and -independent apoptosis.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.2004.02451.x
Permalink
