Abstract
The mode of action of trans-resveratrol, a promising lead compound for the development of neuroprotective drugs, is unknown. Data from a functional genomics study were retrieved with the aim to find differentially expressed genes that may be involved in the benefits provided by trans-resveratrol. Genes that showed a significantly different expression (p<0.05, cut-off of a two-fold change) in mice fed with a control diet or a control diet containing trans-resveratrol were different in cortex, heart and skeletal muscle. In neocortex, we identified 4 up-regulated (Strap, Pkp4, Rab2a, Cpne3) and 22 down-regulated (Actn1, Arf3, Atp6v01, Atp1a3, Atp1b2, Cacng7, Crtc1, Dbn1, Dnm1, Epn1, Gfap, Hap, Mark41, Rab5b, Nrxn2, Ogt, Palm, Ptprn2, Ptprs, Syn2, Timp2, Vamp2) genes upon trans-resveratrol consumption. Network analysis of gene products provided evidence of plakophilin 4 up-regulation as a triggering factor for down-regulation of events related to synaptic vesicle transport and neurotransmitter release via underexpression of dynamin1 and Vamp2 (synaptobrevin 2) as node-gene drivers. Analysis by RT-qPCR of some of the selected genes in a glioma cell line showed that dynamin 1 mRNA was down-regulated even in acute trans-resveratrol treatments. Taken all together, these results give insight on the glial-neuronal networks involved in the neuroprotective role of trans-resveratrol.
Highlights
Phytochemicals are in the front line to combat oxidative stress, mainly in the central nervous system (CNS), which loses detoxification potential upon aging
The main objective of this work was to study whether RSV affects gene expression in the brain and how this can be related with neuroprotection in neurodegenerative diseases
Our first aim was to analyze whether the effect of RSV in gene expression impacted on the same genes in the three different tissues
Summary
Phytochemicals are in the front line to combat oxidative stress, mainly in the central nervous system (CNS), which loses detoxification potential upon aging. Aging is the main risk factor in the two most prevalent neurodegenerative diseases in Western societies with high life expectances: Parkinson’s (PD) and Alzheimer’s (AD) [1]. Unlike AD [2], PD patients have efficacious therapies that address symptoms but do not result in neuroprotection, i.e. they not impede disease progression [3,4]. 3, 5, 40-trihydroxy-stilbene, commonly known as resveratrol, is among the most promising natural compounds with neuroprotective potential. Interest in resveratrol came from noticing that part of the benefits Mediterranean diet were due to consumption of wine, which is considered the main natural source of the compound. Resveratrol naturally exists in cis- and trans-configurations trans-resveratrol (RSV) seems to be the most biologically active isomer
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