Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression

Abstract

Brain derived neurotrophic factor (BDNF) is linked to the pathophysiology of depression. We hypothesized that BDNF is one of the neurobiological pathways related to the augmentation effect of alpha-lipoic acid (ALA) when associated with antidepressants. Female mice were administered vehicle or CORT 20mg/kg during 14 days. From the 15th to 21st days the animals were divided in groups that were further administered: vehicle, desvenlafaxine (DVS) 10 or 20mg/kg, ALA 100 or 200mg/kg or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200 or DVS20+ALA200. ALA or DVS alone or in combination reversed CORT-induced increase in immobility time in the forced swimming test and decrease in sucrose preference, presenting, thus, an antidepressant-like effect. DVS10 alone reversed CORT-induced decrease in BDNF in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). The same was observed in the HC and ST of ALA200 treated animals. The combination of DVS and ALA200 reversed CORT-induced alterations in BDNF and even, in some cases, increased the levels of this neurotrophin when compared to vehicle-treated animals in HC and ST. Taken together, these results suggest that the combination of the DVS+ALA may be valuable for treating conditions in which BDNF levels are decreased, such as depression.

Antidepressant-like activity of red wine phenolic extracts in repeated corticosterone-induced depression mice via BDNF/TrkB/CREB signaling pathway

“…Circadian rhythm is modulated by corticosteroids secretion, which is regulated by the hypothalamuspituitary-adrenal gland axis (Llansola et al, 2013). It was observed in our study that repeated corticosterone treatment caused an elevation of serum corticosterone levels in mice, which was consistent with the previous studies (Sousa et al, 2015). This means that exogenous corticosterone results in an absolute increase in circulating serum corticosterone levels, an indicator of stress and depression in mice.…”

“…Corticosterone (TCI, Japan) was dissolved in saline containing 0.1% dimethyl sulfoxide (DMSO) and 0.1% Tween-80. Corticosterone was injected subcutaneously once a day, between 09:00 and 11:30 a.m. (Sousa et al, 2015), at 40 mg/kg in a volume of 1 ml/kg as this dose reliably increases depression-like behavior in mice without altering the nonspecific motor activity (Fenton et al, 2015). Control mice received the same volume of saline.…”

Anti-depressant effects of oil from fructus gardeniae via PKA-CREB-BDNF signaling

“…BDNF is one of the major downstream target genes of CREB, which is the most prevalent neurotropic factor in the cerebral dysfunction. BDNF is also acknowledged as one of the most extensively investigated target molecules controlling brain plasticity, survival, and differentiation in both periphery and central nervous system (CNS) [25]. Studies have shown that the non-polar extract of Gardenia Jasminoides has a rapid antidepressant activity, which mainly depends on the BDNF-TrkB signaling [9].…”

Mitochondrial Agents for Bipolar Disorder

“…In a corticosterone-induced model of depression in mice, ALA showed antidepressant properties and reversed brain-derived neurotrophic factor reduction in the hippocampus and striatum ( de Sousa et al, 2015 ). In a d-amphetamine-induced model of mania, ALA was able to both prevent and reverse symptoms with comparable efficiency to lithium ( Macêdo et al, 2012 ).…”