Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection

Xu, Yun; Zhang, Wenri; Klaus, Judith A.; Young, Jennifer M.; Koerner, Ines P.; Sheldahl, Laird C; Hurn, Patricia D.; Martínez-Murillo, Francisco; Alkayed, Nabil J.

doi:10.1073/pnas.0602932103

Cited by 108 publications

(100 citation statements)

References 44 publications

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“…A recent study showed that CART is highly induced by E in the cerebral cortex during ischemia, suggesting that the up-regulation of this neuropeptide by E may play a role in neuroprotection (Xu et al 2006). In our study without insult, CART mRNA was decreased by E administration but there was no effect on the peptide.…”

Section: Cart Estrogen and Neuroprotectionmentioning

confidence: 99%

Unique responses of midbrain CART neurons in macaques to ovarian steroids

et al. 2008

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CART (cocaine and amphetamine regulated transcript) is a neuropeptide involved in the control of several physiological processes, such as response to psychostimulants, food intake, depressive diseases and neuroprotection. It is robustly expressed in the brain, mainly in regions that control emotional and stress responses and it is regulated by estrogen in the hypothalamus. There is a distinct population of CART neurons located in the vicinity of the Edinger-Westphal nucleus of the midbrain that also colocalize urocortin-1. The aims of this study were 1) to determine the distribution of CART immunoreactive neurons in the monkey midbrain, 2) to examine the effects of estrogen (E) and progesterone (P) on midbrain CART mRNA and peptide expression and 3) to determine whether midbrain CART neurons contain steroid receptors. Adult female rhesus monkeys (Macaca mulatta) were spayed and either treated with placebo (OVX), estrogen alone (E), progesterone alone (P) or E + P. Animals were prepared (a) for RNA extraction followed by microarray analysis and quantitative (q) RT-PCR (n=3/group); (b) for immunohistochemical analysis of CART and CART +tryptophan hydroxylase (TPH), CART+estrogen receptors (ER) or CART+progesterone receptors (n=5/group) and (c) for western blots (n=3/group). Both E− and E+P-administration decreased CART gene expression on the microarray and with qRT-PCR. Stereological analysis of CART immunostaining at five levels of the Edinger-Westphal nucleus indicated little effect of E or E + P administration on the area of CART immunostaining. However, P administration increased CARTimmunopositive area in comparison to the OVX control group with Student's t-test, but not with ANOVA. CART 55-102 detection on western blot was unchanged by hormone administration. ERβand PR were detected in CART neurons and CART fibers appeared to innervate TPH-positive serotonin neurons in the dorsal raphe. In summary, E decreased CART mRNA, but this effect did not translate to the protein level. Moreover, P administration alone had a variable effect on CART mRNA, but it caused an increase in CART immunostaining. Together, the data suggest that CART neurons in the midbrain have a unique steroid response, which may be mediated by nuclear receptors, neuroactive steroids or interneurons.

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Section: Cart Estrogen and Neuroprotectionmentioning

confidence: 99%

Unique responses of midbrain CART neurons in macaques to ovarian steroids

et al. 2008

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“…Primary cortical neuron culture was carried out as described (Xu et al, 2006). Briefly, neurons were isolated from each embryonic cortex (E15-E17 wild-type B6 mouse) and maintained in Neurobasal media supplemented with B27 (Invitrogen, Carlsbad, CA, USA) and 25 nM glutamine at 37°C in a humidified 5% CO 2 incubator.…”

Section: Primary Cortical Neuron Culture and Treatmentmentioning

confidence: 99%

Hopeahainol A attenuates memory deficits by targeting β‐amyloid in APP/PS1 transgenic mice

Zhu

et al. 2012

Aging Cell

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SummaryIncreasing evidence demonstrates that amyloid beta (Ab) elicits mitochondrial dysfunction and oxidative stress, which contributes to the pathogenesis of Alzheimer's disease (AD). Identification of the molecules targeting Ab is thus of particular significance in the treatment of AD. Hopeahainol A (HopA), a polyphenol with a novel skeleton obtained from Hopea hainanensis, is potentially acetylcholinesterase-inhibitory and anti-oxidative in H 2 O 2 -treated PC12 cells. In this study, we reported that HopA might bind to Ab 1-42 directly and inhibit the Ab 1-42 aggregation using a combination of molecular dynamics simulation, binding assay, transmission electron microscopic analysis and staining technique. We also demonstrated that HopA decreased the interaction between Ab 1-42 and Ab-binding alcohol dehydrogenase, which in turn reduced mitochondrial dysfunction and oxidative stress in vivo and in vitro. In addition, HopA was able to rescue the long-term potentiation induction by protecting synaptic function and attenuate memory deficits in APP/PS1 mice. Our data suggest that HopA might be a promising drug for therapeutic intervention in AD.

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“…CART codes for a peptide that has been implicated in a variety of brain functions, including the protection offered by estradiol against ischemic brain injury in stroke and other neurodegenerative diseases (Xu et al, 2006). CART was found to be 2-fold overexpressed in pooled samples from infected animals vs. the control pool.…”

Section: Degeneration Of Synapses Associated De Genes In Bse-infectedmentioning

confidence: 99%

Microarray analysis in caudal medulla of cattle orally challenged with bovine spongiform encephalopathy

Almeida

Basu²,

Williams³

et al. 2011

Genet. Mol. Res.

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ABSTRACT. Bovine spongiform encephalopathy (BSE) is a fatal disorder in cattle characterized by progressive neurodegeneration of the central nervous system. We investigated the molecular mechanisms involved in neurodegeneration during prion infection through the identification of genes that are differentially expressed (DE) between experimentally infected and non-challenged cattle. Gene expression of caudal medulla from control and orally infected animals was compared by microarray analysis using 24,000 bovine oligonucleotides representing 16,846 different genes to identify DE genes associated with BSE disease. In total, 182 DE genes were identified between normal and BSE-infected tissues (>2.0-fold change, P < 0.01); 81 DE genes had gene ontology functions, which included synapse function, calcium ion regulation, immune and inflammatory response, apoptosis, and cytoskeleton organization; 13 of these genes were found to be involved in 26 different Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The expression of five DE genes associated with synapse function (tachykinin, synuclein, neuropeptide Y, cocaine, ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 10 (4): 3948-3962 (2011) Microarray analysis of DE genes in BSE-infected medulla 3949amphetamine-responsive transcript, and synaptosomal-associated protein 25 kDa) and three DE genes associated with calcium ion regulation (parvalbumin, visinin-like, and cadherin) was further validated in the medulla tissue of cattle at different infection times (6, 12, 42, and 45 months post-infection) by qRT-PCR. These data will contribute to a better understanding of the molecular mechanisms of neuropathology in bovine species.

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Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection

Cited by 108 publications

References 44 publications

Unique responses of midbrain CART neurons in macaques to ovarian steroids

Unique responses of midbrain CART neurons in macaques to ovarian steroids

Hopeahainol A attenuates memory deficits by targeting β‐amyloid in APP/PS1 transgenic mice

Microarray analysis in caudal medulla of cattle orally challenged with bovine spongiform encephalopathy

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