Hippocampus Metabolic Disturbance and Autophagy Deficiency in Olfactory Bulbectomized Rats and the Modulatory Effect of Fluoxetine

Abstract

An olfactory bulbectomy (OBX) rodent is a widely-used model for depression (especially for agitated depression). The present study aims to investigate the hippocampus metabolic profile and autophagy-related pathways in OBX rats and to explore the modulatory roles of fluoxetine. OBX rats were given a 30-day fluoxetine treatment after post-surgery rehabilitation, and then behavioral changes were evaluated. Subsequently, the hippocampus was harvested for metabonomics analysis and Western blot detection. As a result, OBX rats exhibited a significantly increased hyperemotionality score and declined spatial memory ability. Fluoxetine reduced the hyperemotional response, but failed to restore the memory deficit in OBX rats. Sixteen metabolites were identified as potential biomarkers for the OBX model including six that were rectified by fluoxetine. Disturbed pathways were involved in amino acid metabolism, fatty acid metabolism, purine metabolism, and energy metabolism. In addition, autophagy was markedly inhibited in the hippocampus of OBX rats. Fluoxetine could promote autophagy by up-regulating the expression of LC3 II, beclin1, and p-AMPK/AMPK, and down-regulating the levels of p62, p-Akt/Akt, p-mTOR/mTOR, and p-ULK1/ULK1. Our findings indicated that OBX caused marked abnormalities in hippocampus metabolites and autophagy, and fluoxetine could partly redress the metabolic disturbance and enhance autophagy to reverse the depressive-like behavior, but not the memory deficits in OBX rats.

Nutritional Indices for Assessing Fatty Acids: A Mini-Review

“…Epidemiological studies and clinical trials showed that fatty acids are associated with cardiovascular diseases [ 1 , 2 , 3 , 4 , 5 ], neurological diseases [ 6 , 7 , 8 , 9 ], non-alcoholic fatty liver disease [ 10 , 11 , 12 , 13 ], allergic diseases [ 14 , 15 , 16 ], and so on. Evidence from metabolomics experiments indicates that they participate in the metabolic pathways of related diseases [ 8 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. For example, the free FA profile was found to be altered in both leukemia and pre-leukemic diseases, particularly C14:0, C16:0, and C18:0 [ 26 ].…”

EA Ameliorated Depressive Behaviors in CUMS Rats and Was Related to Its Suppressing Autophagy in the Hippocampus

“…Hence, autophagy was inhibited in the hippocampus of OBX rats (a depression animal model) and upregulated by fluoxetine (a widely used antidepressant belonging to selective serotonin reuptake inhibitors (SSRIs)) with reversal of depressive-like behavior and enhanced expression of LC3-II, Beclin1, etc. [ 13 ]. Other studies also presented decreased autophagic markers [ 14 , 15 ].…”

Ocimum basilicum (Basil) Modulates Apoptosis and Neurogenesis in Olfactory Pulp of Mice Exposed to Chronic Unpredictable Mild Stress

“…Olfactory dysfunction is considered a premotor sign of neurodegeneration that appears early in the degenerative process as in Alzheimer disease and Parkinson disease ( 30 , 31 ). Moreover, the olfactory bulbectomy of rats has been validated as a model of depression over the past 30 years, suggesting a close relationship between MOB and depression ( 15 – 17 ). Reviewing literature showed that the, pathophysiology of MOB induced by CUMS is still unclear.…”

“…Although the relationship between MOB and depression was recently reported ( 15 – 17 ), the CUMS-induced dysfunction of MOB is not clearly described. Therefore, the current research was designed to evaluate the CUMS-induced alterations occurred in MOB in mice exposed to mild chronic depression and the efficacy of inhalation of O. basilicum essential oils in improving these changes as well as understand the possible mechanism underlying this effect.…”