BDNF-GSK-3β-β-Catenin Pathway in the mPFC Is Involved in Antidepressant-Like Effects ofMorinda officinalisOligosaccharides in Rats

Abstract

Background Morinda officinalis oligosaccharides have been reported to exert neuroprotective and antidepressant-like effects in the forced swim test in mice. However, the mechanisms that underlie the antidepressant-like effects of Morinda officinalis oligosaccharides are unclear.MethodsChronic unpredictable stress and forced swim test were used to explore the antidepressant-like effects of Morinda officinalis oligosaccharides and resilience to stress in rats. The phosphoinositide-3 kinase inhibitor LY294002 was microinjected in the medial prefrontal cortex to explore the role of glycogen synthase kinase-3β in the antidepressant-like effects of Morinda officinalis oligosaccharides. The expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase 3β, β-catenin, and synaptic proteins was determined in the medial prefrontal cortex and the orbitofrontal cortex by western blot.ResultsWe found that Morinda officinalis oligosaccharides effectively ameliorated chronic unpredictable stress-induced depression-like behaviors in the sucrose preference test and forced swim test. The Morinda officinalis oligosaccharides also significantly rescued chronic unpredictable stress-induced abnormalities in the brain-derived neurotrophic factor-glycogen synthase kinase-3β-β-catenin pathway and synaptic protein deficits in the medial prefrontal cortex but not orbitofrontal cortex. The activation of glycogen synthase kinase-3β by the phosphoinositide-3 kinase inhibitor LY294002 abolished the antidepressant-like effects of Morinda officinalis oligosaccharides in the forced swim test. Naïve rats that were treated with Morinda officinalis oligosaccharides exhibited resilience to chronic unpredictable stress, accompanied by increases in the expression of brain-derived neurotrophic factor, phosphorylated-Ser9-glycogen synthase kinase-3β, and β-catenin in the medial prefrontal cortex.ConclusionOur findings indicate that the brain-derived neurotrophic factor-glycogen synthase kinase-3β-β-catenin pathway in the medial prefrontal cortex may underlie the antidepressant-like effect of Morinda officinalis oligosaccharides and resilience to stress.

Morinda officinalis oligosaccharides ameliorate depressive‐like behaviors in poststroke rats through upregulating GLUT3 to improve synaptic activity

“…MOOs have been reported to possess antidepressive and neurotrophic properties. 22,24,57 MOOs promote many beneficial processes including neuron survival, 24,58 and also increase protein level of monoamines, as well as BDNF in the hippocampus. 58 However, the antidepressive effect of MOOs in PSD models has not been tested.…”

“…Several studies have reported that MOOs can upregulate monoamine levels in rodent depression models, as well as brain-derived neurotrophic factor (BDNF), which are all hallmarks of amelioration of depression. 20,22 MOOs have also been reported to enhance energy metabolism and inhibit neuronal apoptosis. 23,24 In this study, we found MOOs could ameliorate depressive-like behaviors and glucose metabolism in the medial prefrontal cortex (mPFC) of PSD rat models through upregulating GLUT3 expression, which ultimately enhanced the synaptic activity.…”

<p>The Role of Brain Derived Neurotrophic Factor in HIV-Associated Neurocognitive Disorder: From the Bench-Top to the Bedside</p>

“…BDNF inhibits GSK3B activity by binding to TrKB to activate PI3K and Akt. 57 BDNF modulation may therefore be a mechanism by which GSK3B inhibitors like Lithium and sodium valproate ameliorate HIV-1 mediated neurotoxicity. 55…”

Decreased Density of Perineuronal Net in Prelimbic Cortex Is Linked to Depressive-Like Behavior in Young-Aged Rats

“…The protocols for sample preparation and Western blot were based on previous studies (Xu et al, 2017;Han et al, 2019). One day after the behavioral tests, the rats were decapitated and the brains were rapidly extracted and frozen in −60 • C N-hexane.…”