Incensole acetate reduces depressive-like behavior and modulates hippocampal BDNF and CRF expression of submissive animals

Abstract

Incensole acetate (IA), a constituent of Boswellia resin ('frankincense'), was previously demonstrated to exhibit an antidepressive-like effect in the Forced Swim Test (FST) in mice following single dose administration (50 mg/kg). Here, we show that acute administration of considerably lower dose (10 mg/kg) IA to selectively bred mice, showing prominent submissive behavior, exerted significant antidepressant-like effects in the FST. Furthermore, chronic administration of 1 or 5 mg/kg per day of IA for three consecutive weeks dose- and time-dependently reduced the submissiveness of the mice in the Dominant-Submissive Relationship test, developed to screen the chronic effect of antidepressants. This behavioral effect was concomitant to reduced serum corticosterone levels, dose-dependent down-regulation of corticotropin releasing factor and up-regulation of brain derived neurotrophic factor transcripts IV and VI expression in the hippocampus. These data suggest that IA modulates the hypothalamic-pituitary-adrenal (HPA) axis and influences hippocampal gene expression, leading to beneficial behavioral effects supporting its potential as a novel treatment of depressive-like disorders.

Impact of the Association of a High Fructose Diet and Chronic Mild Stress on Metabolic and Affective Disorders in Male Rat

“…This structure receives nerve fibers from the CRF neurons of PVN of the hypothalamus, central amygdala, and innervates the PVN with noradrenergic nerve fibers [27]. Following exposure to CMS or the combination of a high-fructose diet and CMS, depressive behavior is well established as confirmed by the decrease in sucrose preference, these results are in accordance with current literature [28] [29]. The major system that responds to stress is the corticotropic axis.…”

Endocannabinoid Receptor Deficiency Affects Maternal Care and Alters the Dam's Hippocampal Oxytocin Receptor and Brain‐Derived Neurotrophic Factor Expression

“…We also measured hippocampal BDNF mRNA expression, a well established correlate of stress . Early studies showed that acute or chronic stress decreased BDNF expression in the hippocampus of rodents .…”

Placental glucocorticoid receptor and 11β-hydroxysteroid dehydrogenase-2 recruitment indicates impact of prenatal adversity upon postnatal development in mice

“…Nonetheless, the serum corticosterone concentrations of PRStreated dams showed no inter-strain differences, in agreement with our unpublished findings indicating Dom and Sub mice to undergo similar acute-phase serum corticosterone elevations in response to acute stressors such as restraint or water immersion. The heightened sensitivity to stress of Sub mice has been more apparent in their long-term adaptation to stress (Gross & Pinhasov, 2016;Gross et al, 2017;Moussaieff et al, 2012), as seen presently in markedly heightened serum corticosterone concentrations following repeated restraint stress on GD19 (Figure 2(B)). Thus, the current findings enabled measurement of the subsequent influence of strain-dependent differences in effects of PRS upon developmental programing.…”

“…Mice were culled between 09:00 and 12:00 h, the nadir of corticosterone concentrations among mice maintained in the current colony illumination conditions (Amico, Mantella, Vollmer, & Li, 2004). Circulating corticosterone concentrations were measured in serum samples prepared from trunk blood collected immediately after euthanasia with CO 2 inhalation (Fomby, Wheat, Hatter, Tuttle, & Black, 2004) and stored on ice for 1 h before centrifuging at 3500g for 7 min, as previously (Gross, Nesher, Tikhonov, Raz, & Pinhasov, 2013;Moussaieff et al, 2012), and stored at À20 C for <1 month before analysis using a commercial ELISA kit (DRG EIA-4164, Marburg, Germany; average. inter-and intra-assay CV: 6.01 and 3.09%; assay sensitivity: 0.57 ng/ml) detecting total serum corticosterone (Kinn Rod, Harkestad, Jellestad, & Murison, 2017;Mattos et al, 2013).…”