N-3 polyunsaturated fatty acids and 17β-estradiol injection induce antidepressant-like effects through regulation of serotonergic neurotransmission in ovariectomized rats

Jin, Youri; Park, Yongsoon

doi:10.1016/j.jnutbio.2015.04.005

Cited by 28 publications

(12 citation statements)

References 42 publications

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“…Several reports have shown that n-3 PUFAs could increase CREB expression and pCREB in depression animal models [59]. In agreement with these reports, DHA and EPA increased pCREB in patient-derived astrocytes, except that CREB expression was not altered by n-3 PUFAs in this study.…”

Section: Discussionsupporting

confidence: 92%

N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells

Wang

Sheridan

et al. 2020

Preprint

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30Evidence from epidemiological and laboratory studies, as well as randomized placebo-controlled 31 trials, suggests supplementation with n-3 polyunsaturated fatty acids (PUFAs) may be efficacious 32 for treatment of major depressive disorder (MDD). The mechanisms underlying n-3 PUFAs 33 potential therapeutic properties remain unknown. There are suggestions in the literature that glial 34 hypofunction is associated with depressive symptoms and that antidepressants may normalize 35 glial function. In this study, iPSC-derived neuronal stem cell lines were generated from 36 individuals with MDD. Astrocytes differentiated from patient-derived neuronal stem cells 37 (iNSCs) were verified by GFAP. Cells were treated with eicosapentaenoic acid (EPA), 38 docosahexaenoic acid (DHA) and stearic acid (SA). During astrocyte differentiation, we found 39 that n-3 PUFAs increased GFAP expression and GFAP positive cell formation. BDNF and 40 GDNF production were increased in the astrocytes derived from patients subsequent to n-3 41 PUFA treatment. Stearic Acid (SA) treatment did not have this effect. CREB activity 42 (phosphorylated CREB) was also increased by DHA and EPA but not by SA. Furthermore, when 43 these astrocytes were treated with n-3 PUFAs, the cAMP antagonist, RP-cAMPs did not block n-44 3 PUFA CREB activation. However, the CREB specific inhibitor (666-15) diminished BDNF 45 and GDNF production induced by n-3 PUFA, suggesting CREB dependence. Together, these 46 results suggested that n-3 PUFAs facilitate astrocyte differentiation, and may mimic effects of 47 some antidepressants by increasing production of neurotrophic factors. The CREB-dependence 48 and cAMP independence of this process suggests a manner in which n-3 PUFA could augment 49 antidepressant effects. These data also suggest a role for astrocytes in both MDD and 50 antidepressant action. 51 52 53Major depressive disorder (MDD) is the most common psychiatric disorder, with almost 54 one in six individuals experiencing at least one depressive episode at some point in their lifetime. 55It is currently the leading cause of disability worldwide [1, 2]. While effective treatments exist, 56 about one third of patients treated with antidepressants do not reach symptomatic remission [3, 57 4]. While some of these non-remitters may respond to ketamine or other rescue strategies, 58 additional therapeutic options are needed. 59Brain regions and even cell-types contributing to MDD are not well established [4]. 60Evidence from clinical, preclinical and post-mortem studies suggests that dysfunction and 61 degeneration of astrocytes may be one of potential candidates, and astrocytes may also represent 62 a potential therapeutic target for MDD [5][6][7][8]. Antidepressants, including SSRIs and ketamine, 63 increase brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor 64 (GDNF) expression in primary cultured animal astrocytes [9][10][11]. Substantial evidence suggested 65 that astrocytes might be the main resource of antidepressant...

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Section: Discussionsupporting

confidence: 92%

N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells

Wang

Sheridan

et al. 2020

Preprint

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“…Another study shows that EPA and DHA present similar antidepressants effects of 17β-estradiol by regulating serotonergic neurotransmission and decreasing the synthesis of inflammatory cytokines [15].…”

Section: Discussionmentioning

confidence: 96%

Determination of Omega-3/Omega-6 Ratio in Swine Brain Homogenate as an Animal Model for Human Nervous Tissue

Tero-Vescan

Ősz

Vari

et al. 2016

Acta Medica Marisiensis

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Objectives: The purpose of the study was to determine the omega-3/omega-6 ratio in swine brain homogenate by HPLC with UV detection and to discuss the values obtained by comparison to the human species. Materials and methods: Determinations were performed by HPLC method using as mobile phase an isocratic mixture (A:B -5:95) of mobile phase A = 25% acetonitrile in water and B = acetonitrile with a flow-rate of 1.2 mL/min and UV detection at 205nm. Chromatographic column: Phenomenex C8 150x4.6 mm 5μm. 50 g swine brain was hydrolyzed with 100 mL 0.5N HCl, the organic phase was extracted in 50 mL hexane, concentrated by evaporation and resumed in 200 μL acetonitrile. Results: Polyunsaturated fatty acids were separated as follows arachidonic acid (AA) -Rt = 2.69 min, docosahexaenoic acid (DHA) -Rt = 3.12 min and eicosapentaenoic acid (EPA) -Rt = 3.97 min. The following omega-3/omega-6 ratios were calculated (DHA + EPA)/ AA = 0.572 ± 0.451, EPA/AA = 0.027 ± 0.015 and DHA/AA = 0.689 ± 0.612. Conclusions: The values obtained for these ratios should be balanced, but in reality they are in favor of the ratio denominator. Considering the physiological and nutritional similarities and that an accurate diagnosis of neurodegenerative disease is set in post-mortem, swine brain homogenate could serve as an animal model for human nervous tissue.

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“…Likely, the best characterized evidence of the DHA and E2 interplay in humans is the demonstration of a higher prevalence rate of depression following DHA deficiency and ovarian hormonal dysregulation (Davis et al, 2010 ). Indeed, it has been reported a synergistic antidepressant action of DHA and E2 in the regulation of serotonergic neurotransmission through brain-derived neurotrophic factor (BDNF) and inflammatory cytokines (Jin and Park, 2015 ). These antidepressant-like effects were specific of DHA since its precursor alpha-linolenic acid did not show any effect in serotonergic circuits (Choi and Park, 2017 ).…”

Section: Estrogen As Lipostatic Agent In Neuronal Membranesmentioning

confidence: 99%

Estrogen Interactions With Lipid Rafts Related to Neuroprotection. Impact of Brain Ageing and Menopause

Marín

Dı́az

2018

Front. Neurosci.

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Estrogens (E2) exert a plethora of neuroprotective actions against aged-associated brain diseases, including Alzheimer's disease (AD). Part of these actions takes place through binding to estrogen receptors (ER) embedded in signalosomes, where numerous signaling proteins are clustered. Signalosomes are preferentially located in lipid rafts which are dynamic membrane microstructures characterized by a peculiar lipid composition enriched in gangliosides, saturated fatty acids, cholesterol, and sphingolipids. Rapid E2 interactions with ER-related signalosomes appear to trigger intracellular signaling ultimately leading to the activation of molecular mechanisms against AD. We have previously observed that the reduction of E2 blood levels occurring during menopause induced disruption of ER-signalosomes at frontal cortical brain areas. These molecular changes may reduce neuronal protection activities, as similar ER signalosome derangements were observed in AD brains. The molecular impairments may be associated with changes in the lipid composition of lipid rafts observed in neurons during menopause and AD. These evidences indicate that the changes in lipid raft structure during aging may be at the basis of alterations in the activity of ER and other neuroprotective proteins integrated in these membrane microstructures. Moreover, E2 is a homeostatic modulator of lipid rafts. Recent work has pointed to this relevant aspect of E2 activity to preserve brain integrity, through mechanisms affecting lipid uptake and local biosynthesis in the brain. Some evidences have demonstrated that estrogens and the docosahexaenoic acid (DHA) exert synergistic effects to stabilize brain lipid matrix. DHA is essential to enhance molecular fluidity at the plasma membrane, promoting functional macromolecular interactions in signaling platforms. In support of this, DHA detriment in neuronal lipid rafts has been associated with the most common age-associated neuropathologies, namely AD and Parkinson disease. Altogether, these findings indicate that E2 may participate in brain preservation through a dual membrane-related mechanism. On the one hand, E2 interacting with ER related signalosomes may protect against neurotoxic insults. On the other hand, E2 may exert lipostatic actions to preserve lipid balance in neuronal membrane microdomains. The different aspects of the emerging multifunctional role of estrogens in membrane-related signalosomes will be discussed in this review.

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N-3 polyunsaturated fatty acids and 17β-estradiol injection induce antidepressant-like effects through regulation of serotonergic neurotransmission in ovariectomized rats

Cited by 28 publications

References 42 publications

N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells

N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells

Determination of Omega-3/Omega-6 Ratio in Swine Brain Homogenate as an Animal Model for Human Nervous Tissue

Estrogen Interactions With Lipid Rafts Related to Neuroprotection. Impact of Brain Ageing and Menopause

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