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

Abstract

Poststroke depression (PSD) is one of the most common psychiatric diseases afflicting stroke survivors, yet the underlying mechanism is poorly understood. The pathophysiology of PSD is presumably multifactorial, involving ischemia‐induced disturbance in the context of psychosocial distress. The homeostasis of glucose metabolism is crucial to neural activity. In this study, we showed that glucose consumption was decreased in the medial prefrontal cortex (mPFC) of PSD rats. The suppressed glucose metabolism was due to decreased glucose transporter‐3 (GLUT3) expression, the most abundant and specific glucose transporter of neurons. We also found Morinda officinalis oligosaccharides (MOOs), approved as an antidepressive Chinese medicine, through upregulating GLUT3 expression in the mPFC, improved glucose metabolism, and enhanced synaptic activity, which ultimately ameliorated depressive‐like behavior in PSD rats. We further confirmed the mechanism that MOOs induce GLUT3 expression via the PKA/pCREB pathway in PSD rats. Our work showed that MOOs treatment is capable of restoring GLUT3 level to improve depressive‐like behaviors in PSD rats. We also propose GLUT3 as a potential therapeutic target for PSD and emphasize the importance of metabolism disturbance in PSD pathology.

WITHDRAWN: Morinda officinalis oligosaccharides alleviate depressive-like behaviors in post-stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation

“…This study was performed under the Institutional Guidelines of the Animal Care and Use Committee, Huazhong University of Science and Technology. To produce the PSD model, transient middle cerebral artery occlusion (tMCAO) operation was performed on Male Sprague-Dawley rats (250-280 g) in accordance with previously described procedures [7]. The lament was withdrawn for reperfusion after 2 hours of tMCAO.…”

“…Immuno uorescence was performed as described [7]. The rats' brains were xed with 4% paraformaldehyde and then cut into 20 mm sections.…”

“…In our previous study, we found that PSD rats showed suppressed glucose metabolism due to decreased glucose transporter-3 expression in the neurons of medial prefrontal cortex but not in the hippocampus, which was responsible for the occurrence of PSD [7]. However, hippocampus is demonstrated to be an important regulator of emotion and cognition in the brain [8,9], and evidence has also suggested the correlation among depression, hippocampal in ammation and stroke.…”

Morinda officinalis oligosaccharides alleviate depressive‐like behaviors in post‐stroke rats via suppressing NLRP3 inflammasome to inhibit hippocampal inflammation

“…Immunofluorescence was performed as previously described. 7 The rats' brains were fixed with 4% paraformaldehyde and then cut into 20-mm sections. The following primary antibodies were used:…”

Electroacupuncture Ameliorates Depressive-Like Behaviors in Poststroke Rats via Activating the tPA/BDNF/TrkB Pathway

“…4 However, SSRI administration raises the risk of cerebral hemorrhage and other side effects. 5 It has been suggested that brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiological mechanisms of PSD. 6 Decreased concentration of serum BDNF has been demonstrated in patients with PSD.…”