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BackgroundAdult hippocampal neurogenesis has been implicated in the mechanism of antidepressant action, and neurotrophic factors can mediate the neurogenic changes underlying these effects. The neurotrophic factor neuregulin-1 (NRG1) is involved in many aspects of brain development, from cell fate determination to neuronal maturation. However, nothing is known about the influence of NRG1 on neurodevelopmental processes occurring in the mature hippocampus.MethodsAdult male mice were given subcutaneous NRG1 or saline to assess dentate gyrus proliferation and neurogenesis, as well as cell fate determination. Mice also underwent behavioral testing. Expression of ErbB3 and ErbB4 NRG1 receptors in newborn dentate gyrus cells was assessed at various time points between birth and maturity. The phenotype of ErbB-expressing progenitor cells was also characterized with cell type-specific markers.ResultsThe current study shows that subchronic peripheral NRG1β administration selectively increased cell proliferation (by 71%) and neurogenesis (by 50%) in the caudal dentate gyrus within the ventral hippocampus. This pro-proliferative effect did not alter neuronal fate, and may have been mediated by ErbB3 receptors, which were expressed by newborn dentate gyrus cells from cell division to maturity and colocalized with SOX2 in the subgranular zone. Furthermore, four weeks after cessation of subchronic treatment, animals displayed robust antidepressant-like behavior in the absence of changes in locomotor activity, whereas acute treatment did not produce antidepressant effects.ConclusionsThese results show that neuregulin-1β has pro-proliferative, neurogenic and antidepressant properties, further highlight the importance of peripheral neurotrophic factors in neurogenesis and mood, and support the role of hippocampal neurogenesis in mediating antidepressant effects.

he relationship between stress and disease is now well established, but was not always recognised. The word 'stress' is used in physics to refer to the interaction between a force and the resistance to counter that force, and it was Hans Selye who first incorporated this term into the medical lexicon to describe the "nonspecific response of the body to any demand ". Selye, who is known as the 'father of stress research', disavowed the study of specific disease signs and symptoms, unlike others before him, and instead focused on universal patient reactions to illness. His concept of stress impacted scientific and lay communities alike, in fields as diverse as endocrinology, complementary medicine, animal breeding and social psychology.

Plasma aldosterone, deoxycorticosterone (DOC), 18-hydroxy-deoxycorticosterone (18OH-DOC), and corticosterone were measured in Dahl salt-sensitive (S) and salt-resistant (R) rats. Plasma corticosterone and DOC were not different between strains but plasma aldosterone was decreased and plasma 18OH-DOC increased in S compared to R. Plasma renin activity and urinary kallikrein excretion were both lower in S than R. Urinary kallikrein is known to vary directly with mineralocorticoid activity and 18OH-DOC is a weak mineralocorticoid. The lower urinary kallikrein in the presence of elevated 18OH-DOC could mean that urinary kallikrein differences between S and R are under independent genetic control from 18OH-DOC.

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In 12 human volunteers, indomethacin was shown to inhibit renal prostaglandin produciton as reflected by RIA of urinary PGE2. The increases in plasma renin activity and plasma and urinary aldosterone following acute furosemide challenge were markedly blunted in the presence of indomethacin. In light of recent development indicating an intimate relationship between prostaglandins and renin release, these results provide further evidence for a pivotal role of renal prostaglandins in modulating the responsiveness of the renin-angiotensin-aldosterone axis in Mam.

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Hyporeninemic hypoaldosteronism was diagnosed in a young woman with glomerulonephritis who was receiving indomethacin therapy. Despite only mildly abnormal renal function, serum K+ was elevated to 6.2 meq/L, and plasma renin activity (0.12 ng/mL h) and aldosterone (4.4 ng/dL) failed to respond to the combined stimuli of furosemide and posture. Urinary prostaglandin E2 (PGE2) was suppressed (70 ng/24 h). When indomethacin was withdrawn, significant kaliuresis occurred, accompanied by normalization of serum K+ and PGE2 and a supranormal rebound in renin and aldosterone levels. Challenge with indomethacin resulted in antikaliuresis and resuppression of PGE2, renin, and aldosterone. This case study documents for the first time that indomethacin can cause the syndrome of hyporeninemic hypoaldosteronism, probably by inhibiting prostaglandin biosynthesis.