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Striatal modulation of cAMP‐response‐element‐binding protein (CREB) after excitotoxic lesions: implications with neuronal vulnerability in Huntington's disease
Author(s) -
Giampà Carmela,
DeMarch Zena,
D'Angelo Vincenza,
Morello Maria,
Martorana Alessandro,
Sancesario Giuseppe,
Bernardi Giorgio,
Fusco Francesca R.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.04545.x
Subject(s) - creb , quinolinic acid , striatum , endocrinology , medicine , calretinin , neuroscience , neuroprotection , biology , cholinergic , dopamine , biochemistry , amino acid , tryptophan , immunohistochemistry , gene , transcription factor
Recent evidence has shown that the activity of cAMP responsive element‐binding protein (CREB) and of CREB‐binding protein (CBP) is decreased in Huntington's disease (HD) [Steffan et al . (2000) Proc. Natl Acad. Sci. USA , 97, 6763–6768; Gines et al . (2003) Hum. Mol. Genet. , 12, 497–508; Rouaux et al . (2004) Biochem. Pharmacol. , 68, 1157–1164; Sugars et al . (2004) J. Biol. Chem. , 279, 4988–4999]. Such decrease is thought to reflect the impaired energy metabolism observed in a HD mouse model, where a decline in striatum cAMP levels has been observed [Gines et al . (2003) Hum. Mol. Genet. , 12, 497–508]. Increased levels of CREB have also been demonstrated to exert neuroprotective functions [Lonze & Ginty (2002) Neuron , 35, 605–623; Lonze et al . (2002) Neuron , 34, 371–385]. Our study aimed to investigate the distribution of CREB in the neuronal subpopulations of the striatum in normal rats compared to the HD model of quinolinic acid lesion. Twenty‐five Wistar rats were administered quinolinic acid 100 m m into the right striatum, and killed after 24 h, 48 h, 1 week, 2 weeks, and six weeks, respectively. The contralateral striata were used as controls. Dual‐label immunofluorescence was employed using antibodies against phosphorylated CREB and each of the different neuronal subpopulations markers. Our results show that activated CREB levels decrease progressively in projection neurons and parvalbumin (PARV) and calretinin (CALR) interneurons, whereas such levels remain stable in cholinergic and somatostatin interneurons. Thus, we speculate that the ability of cholinergic interneurons to maintain their levels of CREB after excitotoxic lesions is one of the factors determining their protection in Huntington's disease.