Neuronal and Astroglial Localization of Glucocorticoid Receptor GRα in Adult Zebrafish Brain (Danio rerio).

Glucocorticoid receptor α (GRα), a ligand-regulated transcription factor, mainly activated by cortisol in humans and fish, mediates neural allostatic and homeostatic functions induced by different types of acute and chronic stress, and systemic inflammation. Zebrafish GRα is suggested to have multiple transcriptional effects essential for normal development and survival, similarly to mammals. While sequence alignments of human, monkey, rat, and mouse GRs have shown many GRα isoforms, we questioned the protein expression profile of GRα in the adult zebrafish (Danio rerio) brain using an alternative model for stress-related neuropsychiatric research, by means of Western blot, immunohistochemistry and double immunofluorescence. Our results identified four main GRα-like immunoreactive bands (95 kDa, 60 kDa, 45 kDa and 35 kDa), with the 95 kDa protein showing highest expression in forebrain compared to midbrain and hindbrain. GRα showed a wide distribution throughout the antero-posterior zebrafish brain axis, with the most prominent labeling within the telencephalon, preoptic, hypothalamus, midbrain, brain stem, central grey, locus coeruleus and cerebellum. Double immunofluorescence revealed that GRα is coexpressed in TH+, ß2-AR+ and vGLUT+ neurons, suggesting the potential of GRα influences on adrenergic and glutamatergic transmission. Moreover, GRα was co-localized in midline astroglial cells (GFAP+) within the telencephalon, hypothalamus and hindbrain. Interestingly, GRα expression was evident in the brain regions involved in adaptive stress responses, social behavior, and sensory and motor integration, supporting the evolutionarily conserved features of glucocorticoid receptors in the zebrafish brain.

Early life stress induces long-term changes in limbic areas of a teleost fish: the role of catecholamine systems in stress coping.

Early life stress (ELS) shapes the way individuals cope with future situations. Animals use cognitive flexibility to cope with their ever-changing environment and this is mainly processed in forebrain areas. We investigated the performance of juvenile gilthead seabream, previously subjected to an ELS regime. ELS fish showed overall higher brain catecholaminergic (CA) signalling and lower brain derived neurotrophic factor (bdnf) and higher cfos expression in region-specific areas. All fish showed a normal cortisol and serotonergic response to acute stress. Brain dopaminergic activity and the expression of the α2Α adrenergic receptor were overall higher in the fish homologue to the lateral septum (Vv), suggesting that the Vv is important in CA system regulation. Interestingly, ELS prevented post-acute stress downregulation of the α2Α receptor in the amygdala homologue (Dm3). There was a lack of post-stress response in the ß2 adrenergic receptor expression and a downregulation in bdnf in the Dm3 of ELS fish, which together indicate an allostatic overload in their stress coping ability. ELS fish showed higher neuronal activity (cfos) post-acute stress in the hippocampus homologue (Dlv) and the Dm3. Our results show clear long-term effects on limbic systems of seabream that may compromise their future coping ability to environmental challenges.

Evidence of dysregulated affect indicated by high alexithymia in obstructive sleep apnea.

Alexithymia refers to dysregulation of affect characterized by difficulty in identifying and expressing emotions. Obstructive sleep apnea (OSA) is characterized by increased medical/psychiatric comorbidity and possibly by affect dysregulation. In the present case-control study, we examined alexithymia levels with the Toronto Alexithymia Scale (TAS-20) in 23 psychiatrically uncomplicated OSA outpatients and 23 same gender controls one-to-one matched for age, education and subjective depressive symptomatology. General health/quality of life was assessed with the Short-Form 36 Health Survey (SF-36) in the patient group. Hierarchical multivariate regression models were used to evaluate the association of alexithymia with the presence of OSA, and clinical and polysomnographic parameters of this condition. TAS-20 total and subscale scores were associated positively with Beck Depression Inventory (BDI)-21 and negatively with SF-36 scores. After adjusting for all confounders, OSA was positively associated with total TAS-20 score, 'expressing feelings' and 'externally oriented thinking' subscales. The latter was associated with increased sleepiness and reduced blood oxygenation in the OSA group. Finally, 'difficulty describing feelings' and 'externally oriented thinking' significantly predicted risk for OSA. Alexithymia is higher in non-psychiatrically ill patients with OSA compared with carefully matched controls even after adjustment for subjective depressive symptoms and demographic confounders. Total alexithymia is associated with greater subjective depression and poor general health/quality of life, while 'externally oriented thinking' is associated with disease severity and together with 'difficulty describing feelings' may be vulnerability factors for OSA, although reverse causality cannot be excluded.