Acute Inflammation Induces Neuroendocrine and Opioid Receptor Genes Responses in the Seabass Dicentrarchus labrax Brain

Abstract

Simple Summary It is generally accepted (in mammals and in teleost fish, too) that stressful conditions affect the performance of an immune response. What is still far from being known is at what extend does an immune process affects the neuroendocrine system. Vaccination for instance, is nowadays a common practice in aquaculture and little is known about its physiological implications other than immunization. Here is a first approach to the study of the European seabass' brain gene expression patterns in response to a peripheral inflammatory process. Genes related to the stress response were focused, along with those related to the opioid system. Increased expression of certain genes suggests the activation of a stress response triggered by inflammatory signals. Additionally, contrasting expression patterns of the same gene (increased vs decreased) in the different brain regions (as well as the time needed for changes to happen) point at different functions. These results clearly show the reactivity of different brain responses to an immune response, highlighting the importance of further studies on downstream implications (behavior, feeding, welfare, reproduction). In fish, as observed in mammals, any stressful event affects the immune system to a larger or shorter extent. The neuroendocrine-immune axis is a bi-directional network of mobile compounds and their receptors that are shared between both systems (neuroendocrine and immune) and that regulate their respective responses. However, how and to what extent immunity modulates the neuroendocrine system is not yet fully elucidated. This study was carried out to understand better central gene expression response patterns in a high-valued farmed fish species to an acute peripheral inflammation, focusing on genes related to the hypothalamus-pituitary-interrenal axis and the opioid system. European seabass, Dicentrarchus labrax, were intra-peritoneally injected with either Freund's Incomplete Adjuvant to induce a local inflammatory response or Hanks Balances Salt Solution to serve as the control. An undisturbed group was also included to take into account the effects due to handling procedures. To evaluate the outcomes of an acute immune response, fish were sampled at 4, 24, 48, and 72 h post-injection. The brain was sampled and dissected for isolation of different regions: telencephalon, optic tectum, hypothalamus, and pituitary gland. The expression of several genes related to the neuroendocrine response was measured by real-time PCR. Data were statistically analyzed by ANOVA and discriminant analyses to obtain these genes' responsiveness for the different brain regions. Serotonergic receptors were upregulated in the telencephalon, whereas the optic tectum inhibited these transcription genes. The hypothalamus showed a somewhat delayed response in which serotonin and glucocorticoid receptors were concerned. Still, the hypothalamic corticotropin-releasing hormone played an important role in differentiating fish undergoing an inflammatory response from those not under such conditions. Opioid receptors gene expression increased in both the hypothalamus and the telencephalon, while in the optic tectum, most were downregulated. However, no changes in the pituitary gland were observed. The different brain regions under immune stimulation demonstrated clear, distinct responses regarding gene transcription rates as well as the time period needed for the effect to occur.

Further, more integrative studies are required to associate functions to the evaluated genes more safely and better understand the triggering mechanisms.