Foliar application of methyl jasmonate and methyl jasmonate supported on nanoparticles: Incidence on grape phenolic composition over two seasons.

Tools to address the mismatch between technological and phenolic maturity of grapes are needed. Application of elicitors could be an effective alternative. This work compares the effect of the application of methyl jasmonate (MeJ) in conventional form and, as a novelty, in the form of MeJ-doped nanoparticles (ACP-MeJ) on the phenolic composition of Tempranillo grapes. Results showed that, regardless of season, both treatments increased the grape total phenols content. In 2019, most of the anthocyanins, and to a lesser extent the flavanols, increased with the application of MeJ, and several hydroxycinnamic acids increased in the grapes treated with ACP-MeJ, with dose 10 times lower than those of the MeJ conventional. In 2020, anthocyanins were not affected by the treatments, but total flavanols, flavonols, hydroxybenzoic acid, and stilbenes increased after ACP-MeJ application. Thus, foliar application of ACP-MeJ could serve to increase grape phenolic composition, reducing maturity decoupling and the environmental impact.

Aqueous extract of pomegranate enriched in ellagitannins prevents anxiety-like behavior and metabolic changes induced by cafeteria diet in an animal model of menopause.

Women around menopause are vulnerable to present psychiatric and metabolic disorders; thus, therapies that contribute to treat both pathologies are required. Previous reports showed that an aqueous extract of pomegranate (Punica granatum), enriched in ellagitannins, exerts an antidepressant-like effect in ovariectomized rats. We analyze whether this aqueous extract of P. granatum (AE-PG) prevents the anxiety-like behavior induced by a cafeteria diet (CAF) in middle-aged ovariectomized rats at the same time that it prevents an increase in body weight, glucose, lipids, and the changes on mRNA expression of the peroxisome proliferator-activated receptor-gamma (PPAR-γ) in the liver. Also, the effects of AE-PG on the protein levels of PPAR-γphospho-PPAR-γ, extracellular signal-regulated protein kinase (ERK1/2) and phospho-ERK1/2 were measured in the hippocampus and amygdala. CAF induced anxiety-like behavior, augmented lipids and glucose blood levels, body weight, visceral fat, insulin resistance, and decreased mRNA expression of PPAR-γ in the liver. In rats fed with the CAF, AE-PG prevented the anxiety-like behavior, reduced body weight, lowered lipid levels, reduced insulin resistance, and increased PPAR-γ mRNA expression in the liver. In the hippocampus, ERK1/2 but not PPAR-γ protein levels were decreased by CAF, while AE-PG prevented these effects. In the amygdala, CAF increased the phosphorylation of PPARγ, and AE-PG prevented it. In contrast, AE-PG rescued the decreased ERK1/2 protein level in the hippocampus caused by CAF. In conclusion, AE-PG treatment prevented anxiogenic and metabolic effects induced by CAF, and its effects appear to be mediated by ERK1/2 and PPARγ depending on the brain area studied.

Pharmacological inhibition of DNA methyltransferase 1 promotes neuronal differentiation from rodent and human nasal olfactory stem/progenitor cell cultures.

Nasal olfactory stem and neural progenitor cells (NOS/PCs) are considered possible tools for regenerative stem cell therapies in neurodegenerative diseases. Neurogenesis is a complex process regulated by extrinsic and intrinsic signals that include DNA-methylation and other chromatin modifications that could be experimentally manipulated in order to increase neuronal differentiation. The aim of the present study was the characterization of primary cultures and consecutive passages (P2-P10) of NOS/PCs isolated from male Swiss-Webster (mNOS/PCs) or healthy humans (hNOS/PCs). We evaluated and compared cellular morphology, proliferation rates and the expression pattern of pluripotency-associated markers and DNA methylation-associated gene expression in these cultures. Neuronal differentiation was induced by exposure to all-trans retinoic acid and forskolin for 7 days and evaluated by morphological analysis and immunofluorescence against neuronal markers MAP2, NSE and MAP1B. In response to the inductive cues mNOS/PCs expressed NSE (75.67%) and MAP2 (35.34%); whereas the majority of the hNOS/PCs were immunopositive to MAP1B. Treatment with procainamide, a specific inhibitor of DNA methyltransferase 1 (DNMT1), increases in the number of forskolin'/retinoic acid-induced mature neuronal marker-expressing mNOS/PCs cells and enhances neurite development in hNOS/PCs. Our results indicate that mice and human nasal olfactory stem/progenitors cells share pluripotency-related gene expression suggesting that their application for stem cell therapy is worth pursuing and that DNA methylation inhibitors could be efficient tools to enhance neuronal differentiation from these cells.

Dehydroepiandrosterone increases the number and dendrite maturation of doublecortin cells in the dentate gyrus of middle age male Wistar rats exposed to chronic mild stress.

Aging increases the vulnerability to stress and risk of developing depression. These changes have been related to a reduction of dehydroepiandrosterone (DHEA) levels, an adrenal steroid with anti-stress effects. Also, adult hippocampal neurogenesis decreases during aging and its alteration or impaired is related to the development of depression. Besides, it has been hypothesized that DHEA increases the formation of new neurons. However, it is unknown whether treatment with DHEA in aging may stimulate the dendrite maturation of newborn neurons and reversing depressive-like signs evoked by chronic stress exposure. Here aged male rats (14 months old) were subjected to a scheme of chronic mild stress (CMS) during six weeks, received a treatment with DHEA from the third week of CMS. Changes in body weight and sucrose preference (SP) were measured once a week. DHEA levels were measured in serum, identification of doublecortin-(DCX)-, BrdU- and BrdU/NeuN-labeled cells was done in the dentate gyrus of the hippocampus. CMS produced a gradual reduction in the body weight, but no changes in the SP were observed. Treatment enhanced levels of DHEA, but lack of recovery on body weight of stressed rats. Aging reduced the number of DCX-, BrdU- and BrdU/NeuN- cells but DHEA just significantly increased the number of DCX-cells in rats under CMS and controls, reaching levels of young non-stressed rats (used here as a reference of an optimal status of health). In rats under CMS, DHEA facilitated dendritic maturation of immature new neurons. Our results reveal that DHEA improves neural plasticity even in conditions of CMS in middle age rats. Thus, this hormone reverted the decrement of DCX-cells caused during normal aging.

Green tea compound epigallo-catechin-3-gallate (EGCG) increases neuronal survival in adult hippocampal neurogenesis in vivo and in vitro.

Epigallo-catechin-3-gallate (EGCG), found in the leaves of Camellia sinensis (green tea), has antioxidant- and scavenger-functions and acts neuroprotectively. It has been publicized as anti-aging remedy but data on potential cellular mechanisms are scarce. Recent studies claimed that EGCG specifically promotes neural precursor cell proliferation in the dentate gyrus of C57Bl/6 mice, without changes at the level of immature and mature new neurons. We here analyzed the effects of EGCG on adult hippocampal neurogenesis in male Balb/C mice and saw a different pattern. Two weeks of treatment with EGCG (0, 0.625, 1.25, 2.5, 5 and 10mg/kg) showed a dose-response curve that peaked at 2.5mg/kg of EGCG with significantly increased cell survival without affecting cell proliferation but decreasing apoptotic cells. Also, EGCG increased the population of doublecortin-(DCX)-expressing cells that comprises the late intermediate progenitor cells (type-2b and -3) as well as immature neurons. After EGCG treatment, the young DCX-positive neurons showed more elaborated dendritic trees. EGCG also significantly increased net neurogenesis in the adult hippocampus and increased the hippocampal levels of phospho-Akt. Ex vivo, EGCG exerted a direct effect on survival and neuronal differentiation of adult hippocampal precursor cells, which was absent, when PI3K, a protein upstream of Akt, was blocked. Our results thus support a pro-survival and a pro-neurogenic role of EGCG. In the context of the conflicting published results, however, potential genetic modifiers must be assumed. These might help to explain the overall variability of study results with EGCG. Our data do indicate, however, that natural compounds such as EGCG can in principle modulate brain plasticity.