Brain-Derived Neurotrophic Factor Prevents Depressive-Like Behaviors in Early-Symptomatic YAC128 Huntington's Disease Mice.

Huntington disease (HD) is a neurodegenerative disorder caused by an expanded CAG repeat in the Huntington disease gene. The symptomatic stage of the disease is defined by the onset of motor symptoms. However, psychiatric disturbances, including depression, are common features of HD and can occur a decade before the manifestation of motor symptoms. We used the YAC128 transgenic mice (which develop motor deficits at a later stage, allowing more time to study depressive behaviors without the confounding effects of motor impairment) to test the effects of intranasal brain-derived neurotrophic factor (BDNF) treatment for 15 days in the occurrence of depressive-like behaviors. Using multiple well-validated behavioral tests, we found that BDNF treatment alleviated anhedonic and depressive-like behaviors in the YAC128 HD mice. Furthermore, we also investigated whether the antidepressant-like effects of BDNF were associated with an increase in adult hippocampal neurogenesis. However, BDNF treatment only increased cell proliferation and neuronal differentiation in the hippocampal dentate gyrus (DG) of wild-type (WT) mice, without altering these parameters in their YAC128 counterparts. Moreover, BDNF treatment did not cause an increase in the number of dendritic branches in the hippocampal DG when compared with animals treated with vehicle. In conclusion, our results suggest that non-invasive administration of BDNF via the intranasal route may have important therapeutic potential for treating mood disturbances in early-symptomatic HD patients.

Involvement of PI3K/Akt Signaling Pathway and Its Downstream Intracellular Targets in the Antidepressant-Like Effect of Creatine.

Creatine has been proposed to exert beneficial effects in the management of depression, but the cell signaling pathways implicated in its antidepressant effects are not well established. This study investigated the involvement of PI3K/Akt signaling pathway and its downstream intracellular targets in the antidepressant-like effect of creatine. The acute treatment of mice with creatine (1 mg/kg, po) increased the Akt and P70S6K phosphorylation, and HO-1, GPx and PSD95 immunocontents. The pretreatment of mice with LY294002 (10 nmol/mouse, icv, PI3K inhibitor), wortmannin (0.1 µg/mouse, icv, PI3K inhibitor), ZnPP (10 µg/mouse, icv, HO-1 inhibitor), or rapamycin (0.2 nmol/mouse, icv, mTOR inhibitor) prevented the antidepressant-like effect of creatine (1 mg/kg, po) in the TST. In addition, the administration of subeffective dose of either the selective GSK3 inhibitor AR-A014418 (0.01 µg/mouse, icv), the nonselective GSK3 inhibitor lithium chloride (10 mg/kg, po), or the HO-1 inductor CoPP (0.01 µg/mouse, icv), in combination with a subeffective dose of creatine (0.01 mg/kg, po) reduced the immobility time in the TST as compared with either drug alone. No treatment caused significant changes in the locomotor activity of mice. These results indicate that the antidepressant-like effect of creatine in the TST depends on the activation of Akt, Nrf2/HO-1, GPx, and mTOR, and GSK3 inhibition.

Green clay and aloe vera peel-off facial masks: response surface methodology applied to the formulation design.

This article describes the optimization of a peel-off facial mask formulation. An investigation was carried out on the parameters of the formulation that most affect the desirable characteristics of peel-off facial masks. Cereal alcohol had a significant effect on the drying time at concentrations of 1-12% (w/w). The applicability of the evaluated formulations was influenced by both carbomer (0-2.4%; w/w) and polyvinyl alcohol (PVA; 2.5-17.5%; w/w) content due to their ability to alter the formulation viscosity. Inverse concentrations of carbomer and PVA led to formulations with optimum viscosity for facial application. Film-forming performance was influenced only by the PVA concentration, achieving maximum levels at concentrations of around 11% (w/w). The optimized formulation, determined mathematically, contained 13% (w/w) PVA and 10% (w/w) cereal alcohol with no addition of carbomer. This formulation provided high levels of applicability and film-forming performance, the lowest drying time possible and excellent homogeneity of the green clay particles and aloe vera before and after drying. The preliminary stability study indicated that the optimized formulation is stable under normal storage conditions. The microbiological stability evaluation indicated that the preservative was efficient in terms of avoiding microbial growth. RSM was shown to be a useful statistical tool for the determination of the behavior of different compounds and their concentrations for the responses studied, allowing the investigation of the optimum conditions for the production of green clay and aloe vera peel-off facial masks.