Involvement of estrogen receptors in the resveratrol-mediated increase in dopamine transporter in human dopaminergic neurons and in striatum of female mice.

Treatment with resveratrol (RSV) has been shown to protect vulnerable neurons after various brain injuries and in neurodegenerative diseases. The mechanisms for the effects of RSV in brain are not fully understood, but RSV may affect the expression of various gene products. RSV is structurally related to the synthetic estrogen, diethylstilbestrol so the effects of RSV may be gender-specific. Here we studied the role of RSV in the regulation of dopamine transporter (DAT) in the striatum using male and female mice. The basic levels of DAT in the striatum showed no sex difference, but the levels increased significantly by RSV (20 mg/kg i.p.) in female but not in male mice. Pretreatment of mice…

FGF-2/FGFR1 neurotrophic system expression level and its basal activation do not account for the age-dependent decline of precursor cell proliferation in the subventricular zone of rat brain

It is largely accepted that neurogenesis in the adult brain decreases with age and reduced levels of local neurotrophic support is speculated to be a contributing factor. Among neurotrophic factors involved on neurogenesis, we focused our attention on the neurotrophic system fibroblast growth factor-2 (FGF-2) and its receptor FGFR1, a potent modulator of precursor cell proliferation. In the present work, we aimed to analyse if potential age-dependent changes of the FGF-2/FGFR1 neurotrophic system may give account for the age-dependent decline of precursor cell proliferation in the neurogenic region of the subventricular zone (SVZ) in the rat brain. Using in situ hybridization and western bl…

Activation of PGC-1 protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease

Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) is a transcriptional coactivator that is a master regulator of oxidative stress and mitochondrial metabolism. Mitochondrial dysfunction and oxidative stress occur in Parkinson’s disease (PD), but little is known about the molecular mechanisms controlling these events. We report that transgenic mice overexpressing PGC-1 in dopaminergic neurons are resistant against cell degeneration induced by the neurotoxin MPTP. The increase in neuronal viability was accompanied by elevated levels of mitochondrial antioxidants SOD2 and Trx2 in the substantia nigra of transgenic mice. To modulate PGC-1, we employed the small molecula…

Analysis of connexin (Cx36 and Cx45) expression in the carotid body, adrenal medulla and enteric neurons of both mouse and rat

Cx36 and Cx45 are considered the main connexins expressed in neuronal cells of central nervous system (Belluardo N. et al. Brain Res. 2000)), but at present no complete data are available on their expression in the neurons of crest-derived neuroendocrine organ, such as the adrenal medulla, the carotid body and the enteric nervous system. Therefore the present study was undertaken to evaluate using immunohistochemistry and western blotting procedures, both in rat and mouse, whether Cx36 and Cx45 were expressed in neuronal cells of the carotid body, adrenal medulla and myenteric plexus at ileum and colon level. In the carotid body of both mouse and rat only Cx45 was found expressed as diffuse…

Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease

Mitochondrial dysfunction and oxidative stress occur in Parkinson’s disease (PD), but little is known about the molecular mechanisms controlling these events. Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) is a transcriptional coactivator that is a master regulator of oxidative stress and mitochondrial metabolism. We show here that transgenic mice overexpressing PGC-1α in dopaminergic neurons are resistant against cell degeneration induced by the neurotoxin MPTP. The increase in neuronal viability was accompanied by elevated levels of mitochondrial antioxidants SOD2 and Trx2 in the substantia nigra of transgenic mice. PGC-1α overexpression also protected against MP…

HISTONE DEACETYLASE INHIBITORS SENSITIZE HEPATOMA CELLS TO TRAIL_INDUCED APOPTOSIS

Il trattamento con RSV e l’espressione transgenica di PGC-1α proteggono i neuroni dopaminergici nel modello MPTP murino del morbo di Parkinson. Resveratrol treatment and transgenic expression of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease.

Resveratrol increases DAT expression levels in the striatum of female mouse and its effect is mediated by estrogen receptors

Resveratrol (3,4',5-trihydroxystilbene, RSV), a phytoalexins with a stilbene skeleton, exhibits a wide range of biological actions that includes neuroprotective effect against neurodegenerative diseases. In a previous study on RSV neuroprotective effects in mouse Parkinson’s model, we unexpectedly observed an upregulation of DAT in the striatum of female mice treated with RSV. Here we aimed to study in depth the effect of RSV on DAT expression, and additionally to verify the potential involvement of estrogen receptor activation by RSV, according with its striking similarity to the synthetic estrogen diethylstilbestrol. Daily repeated injection of RSV (20 mg/kg i.p.) for four days led, eight…