EPA and DHA, but not ALA, have antidepressant effects with 17ß-estradiol injection via regulation of a neurobiological system in ovariectomized rats.

Our previous studies found that n-3 polyunsaturated fatty acids (PUFAs) and estrogen had synergistic antidepressant-like effects. The purpose of the present study was to investigate the hypothesis that three major n-3 PUFAs, α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), individually had antidepressant effects combined with 17ß-estradiol-3-benzoate (E) through a neurobiological pathway in ovariectomized rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0% n-3 PUFAs and 1% ALA, EPA and DHA relative to total energy intake for 12 weeks and were injected with corn oil or E every 4 days during the last 3 weeks. Supplementation of EPA, DHA and E increased serum concentrations of serotonin and climbing behavior, and decreased immobility during a forced swimming test. Supplementation with EPA, DHA and E also decreased hippocampal expressions of interleukin-6 and tumor necrosis factor-α, and increased cAMP response element binding protein, brain-derived neurotrophic factor (BDNF) and estrogen receptor-α. Immunofluorescence staining consistently showed elevated expressions of BDNF. Magnetic resonance spectroscopy showed that E increased glucose and decreased glutamate, glutamine and myo-inositol concentrations regardless of n-3 PUFA supplementation. In addition, supplementation with EPA, DHA and E decreased levels of nitrite and nitrate. However, ALA had no antidepressant effect. The present study suggested that the antidepressant-like effects of EPA and DHA supplementation and E injection could be due to the regulation of serotonergic neurotransmission and inflammatory cytokines rather than due to the antioxidative system. Supplementation with n-3 PUFA and E had the additional function of modulating neurometabolites in the hippocampus.

Serotonergic chemosensory neurons modify the C. elegans immune response by regulating G-protein signaling in epithelial cells.

The nervous and immune systems influence each other, allowing animals to rapidly protect themselves from changes in their internal and external environment. However, the complex nature of these systems in mammals makes it difficult to determine how neuronal signaling influences the immune response. Here we show that serotonin, synthesized in Caenorhabditis elegans chemosensory neurons, modulates the immune response. Serotonin released from these cells acts, directly or indirectly, to regulate G-protein signaling in epithelial cells. Signaling in these cells is required for the immune response to infection by the natural pathogen Microbacterium nematophilum. Here we show that serotonin signaling suppresses the innate immune response and limits the rate of pathogen clearance. We show that C. elegans uses classical neurotransmitters to alter the immune response. Serotonin released from sensory neurons may function to modify the immune system in response to changes in the animal's external environment such as the availability, or quality, of food.

Comparative morphology of serotonergic-like immunoreactive elements in the central nervous system of kinorhynchs (Kinorhyncha, Cyclorhagida).

Cycloneuralian taxa exhibit similar organ system architectures, providing informative characters of metazoan evolution, yet very few modern comparative descriptions of cellular and molecular homologies within and among those taxa are available. We immunolabeled and characterized elements of the serotonergic nervous system in the kinorhynchs Echinoderes spinifurca, Antygomonas paulae, and Zelinkaderes brightae using confocal laser scanning microscopy. Fluorescent markers targeting DNA were combined with observations of auto-fluorescent structures to guide interpretations of the internal and external anatomy in each species. Results show a common pattern of the central nervous system with a circumenteric brain divided into ring-shaped anterior and posterior neuronal somata and a central neuropil connected to a multi-stringed, longitudinal ventral nerve cord. Structural similarities and differences in the nervous systems of these species were observed and described, stressing the incomplete ring nature of the anterior region of the kinorhynch brain, the functional relationship between the brain and the movable introvert, and the number and arrangement of nerve strings and somata of the ventral nerve cord. The ventral cord ends in two ventrolateral cell bodies in E. spinifurca, and forms a terminal loop associated with a midterminal spine in A. paulae and Z. brightae. The possible functional and phylogenetic significance of these features and arrangements are discussed.