Increased Phospholipase A2 Activity and Inflammatory Response But Decreased Nerve Growth Factor Expression in the Olfactory Bulbectomized Rat Model of Depression: Effects of Chronic Ethyl-Eicosapentaenoate Treatment

Abstract

An increased inflammatory response and deficient synthesis of neurotrophic factors (NTFs) may contribute to the etiology of depression. However, the interrelationship between inflammation and NTFs is unknown. Recently, ethyl-eicosapentaenoate (EPA) has been used to treat depression. The mechanism by which EPA benefits depression is also unclear. Using the olfactory bulbectomized (OB) rat model of depression, this study evaluated two pathways from bulbectomy to the induction of depression-like changes (the inflammation-hypothalamic-pituitary-adrenal axis-stress response pathway and inflammation-nerve growth factor-memory pathway) and the effect of EPA on these pathways. When compared with sham-operated rats fed a control diet, significantly increased locomotor and rearing activities in an "open field," impaired memory in the Morris water maze, increased expression of corticotrophin-releasing factor (CRF), and increased secretion of corticosterone were found in OB rats. mRNA expression of nerve growth factor (NGF) was significantly lower in the hippocampus, and phospholipase A2 (PLA2) was higher in the hypothalamus; this change was associated with increased interleukin-1␤ (IL-1␤) and prostaglandin E2 (PGE2) in the serum and brain. EPA treatments normalized these behavioral impairments and reduced CRF expression and corticosterone secretion. EPA also reduced serum concentrations of IL-1␤ and PGE2, but reversed NGF reduction. Similar to the effects of EPA, the anti-inflammatory drug celecoxib significantly reduced blood PGE2, IL-1␤, and corticosterone concentrations and increased NGF expression in OB rats. Furthermore, anti-NGF treatment blocked EPA effects on behavior. These results suggest that an interaction exists between inflammation and NGF in the depression model. EPA may improve depression via its anti-inflammation properties and the upregulation of NGF.

Toward Omics-Based, Systems Biomedicine, and Path and Drug Discovery Methodologies for Depression-Inflammation Research

“…This is corroborated by reports that nutraceuticals with anti-inflammatory and anti-O&NS effects, which multi-target these pathways [e.g. ω3 PUFAs, zinc, N-acetyl cysteine and curcumin] may have a clinical efficacy in depression and reduce depressive-like behaviors in animal models [4,[78][79][80][81].…”

Exposure to Hypobaric Hypoxia and Reoxygenation Induces Transient Anxiety-Like Behavior in Rat

“…Depressive disorders are marked by chronic depressed mood, inability to experience pleasure, withdrawal of interest, feelings of worthlessness and suicidal tendencies [22,23]. Recent studies shows that stress induced disturbance in cognitive processes, especially impairment of learning and memory functions accelerate onset and development of depressive mood state [24,25]. However, the underlying mechanisms are not clearly understood.…”

“…However, studies in other acute stress model such as restraint and chronic unpredictable mild stress (CUMS) induces anxiety-like behaviors which leads to depressive mood state on prolonged exposure [27][28][29]. Unpredictable chronic mild stress results in depression like behavior in rats and has been used as a well accepted model to study molecular mechanisms underlying depressive disorders [25].…”

The Protective Effects of Omega - 3 Fatty Acids On Prefrontal Cortex Of Brain In Rats

“…25 IL -1 beta ve TNF -alfa gibi proinflamatuar sitokinlerin oluşumu, omega -3 yağ asitleri tarafından azaltılır. 26 Lonergan ve ark.27'nın sıçanlar üzerinde yürütmüş oldukları bir çalışmada, gama radyasyon maruziyeti sonucunda hipokampusta oluşan nöronal hasar üzerine EPA'nın koruyucu bir etki sergilediğini göstermişlerdir. 27 Yine Martin ve ark.28'ları, radyasyon ve yaşa bağlı beyinde oluşan apopitotik zedelenmeler üzerine, EPA'nın elle tutulur düzeyde tamir edici etkisinin olduğunu ortaya koymuşlardır.…”