Hippocampal and behavioral dysfunctions in a mouse model of environmental stress: normalization by agomelatine.

Stress-induced alterations in neuronal plasticity and in hippocampal functions have been suggested to be involved in the development of mood disorders. In this context, we investigated in the hippocampus the activation of intracellular signaling cascades, the expression of epigenetic markers and plasticity-related genes in a mouse model of stress-induced hyperactivity and of mixed affective disorders. We also determined whether the antidepressant drug agomelatine, a MT1/MT2 melatonergic receptor agonist/5-HT2C receptor antagonist, could prevent some neurobiological and behavioral alterations produced by stress. C57BL/6J mice, exposed for 3 weeks to daily unpredictable socio-environmental stressors of mild intensity, were treated during the whole procedure with agomelatine (50 mg kg(-1) per day, intraperitoneal). Stressed mice displayed robust increases in emotional arousal, vigilance and motor activity, together with a reward deficit and a reduction in anxiety-like behavior. Neurobiological investigations showed an increased phosphorylation of intracellular signaling proteins, including Atf1, Creb and p38, in the hippocampus of stressed mice. Decreased hippocampal level of the repressive epigenetic marks HDAC2 and H3K9me2, as well as increased level of the permissive mark H3K9/14ac suggested that chronic mild stress was associated with increased gene transcription, and clear-cut evidence was further indicated by changes in neuroplasticity-related genes, including Arc, Bcl2, Bdnf, Gdnf, Igf1 and Neurod1. Together with other findings, the present data suggest that chronic ultra-mild stress can model the hyperactivity or psychomotor agitation, as well as the mixed affective behaviors often observed during the manic state of bipolar disorder patients. Interestingly, agomelatine could normalize both the behavioral and the molecular alterations induced by stress, providing further insights into the mechanism of action of this new generation antidepressant drug.

Effects of elevated CO2 concentration and water deficit on fructan metabolism in Viguiera discolor Baker.

Elevated [CO2 ] is suggested to mitigate the negative effects of water stress in plants; however responses vary among species. Fructans are recognised as protective compounds against drought and other stresses, as well as having a role as reserve carbohydrates. We analysed the combined effects of elevated [CO2 ] and water deficit on fructan metabolism in the Cerrado species Viguiera discolor Baker. Plants were cultivated for 18 days in open-top chambers (OTC) under ambient (∼380 ppm), and high (∼760 ppm) [CO2 ]. In each OTC, plants were submitted to three treatments: (i) daily watering (control), (ii) withholding water (WS) for 18 days and (iii) re-watering (RW) on day 11. Analyses were performed at time 0 and days 5, 8, 11, 15 and 18. High [CO2 ] increased photosynthesis in control plants and increased water use efficiency in WS plants. The decline in soil water content was more distinct in WS 760 (WS under 760 ppm), although the leaf and tuberous root water status was similar to WS 380 plants (WS under 380 ppm). Regarding fructan active enzymes, 1-SST activity decreased in WS plants in both CO2 concentrations, a result consistent with the decline in photosynthesis and, consequently, in substrate availability. Under WS and both [CO2 ] treatments, 1-FFT and 1-FEH seemed to act in combination to generate osmotically active compounds and thus overcome water deficit. The proportion of hexoses to sucrose, 1-kestose and nystose (SKN) was higher in WS plants. In WS 760, this increase was higher than in WS 380, and was not accompanied by decreases in SKN at the beginning of the treatment, as observed in WS 380 plants. These results suggest that the higher [CO2 ] in the atmosphere contributed to maintain, for a longer period, the pool of hexoses and of low DP fructans, favouring the maintenance of the water status and plant survival under drought.

Fructan composition in adventitious tuberous roots of Viguiera discolor Baker (Asteraceae) as influenced by daylength.

Short (8-10h) photoperiods stimulated branching, flowering and enlargement of adventitious tuberous roots of Viguiera discolor Baker, a native plant of the Brazilian cerrado. Inulin was mostly accumulated in parenchyma cells associated with secondary xylem of tuberous roots. Accumulation was greater in plants grown under conditions that induce flowering (1) than in plants grown under conditions that do not induce flowering (NI) (photoperiods longer than 12 h), Although total fructan concentration was similar in both conditions [approx. 460 mg (g dry mass)-1 ], the amount of inulin in I was 10 times that of oligosaccharides, whereas in NI it was 6 times greater. In addition, the relative molecular mass of inulin was slightly lower in NI 16600) than in I (18600), but considerably higher than those reported for other Asteraceae (approx. 5500). The results suggest that flower-inductive conditions affect fructan metabolism in Viguiera discolor without altering the total fructose.