Fluoxetine Can Cause Epileptogenesis and Aberrant Neurogenesis in Male Wild-Type Mice.

Antidepressants in general, and fluoxetine in particular, increase adult hippocampal neurogenesis (AHN) in mice. Here we asked how the antidepressant fluoxetine affects behavior and AHN in a corticosterone model of depression. In three groups of adult male C57BL/6j mice, we administered either vehicle (VEH), corticosterone (CORT) treatment to induce a depression-like state, or corticosterone plus a standard dose of fluoxetine (CORT+FLX).

Evaluation of Acute Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 Plasma Levels in Traumatic Brain Injury Patients with and without Intracranial Lesions.

This pilot study aimed to evaluate the association of plasma ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein B (S100B) with intracranial abnormalities visible on a computed tomography (CT) scan (CT positive) and injury severity in acute traumatic brain injury (TBI). For these purposes, a cohort of 109 adult TBI patients was recruited within 6 h from the injury event. A hyperacute subcohort of 20 patients who had their blood collected within 2 h from injury was analyzed separately for early acute biomarker levels.

The type of stress matters: repeated injection and permanent social isolation stress in male mice have a differential effect on anxiety- and depressive-like behaviours, and associated biological alterations.

Chronic stress can alter the immune system, adult hippocampal neurogenesis and induce anxiety- and depressive-like behaviour in rodents. However, previous studies have not discriminated between the effect(s) of different types of stress on these behavioural and biological outcomes. We investigated the effect(s) of repeated injection vs.

Chronic stress followed by social isolation promotes depressive-like behaviour, alters microglial and astrocyte biology and reduces hippocampal neurogenesis in male mice.

Unpredictable chronic mild stress (UCMS) is one of the most commonly used, robust and translatable models for studying the neurobiological basis of major depression. Although the model currently has multiple advantages, it does not entirely follow the trajectory of the disorder, whereby depressive symptomology can often present months after exposure to stress. Furthermore, patients with depression are more likely to withdraw in response to their stressful experience, or as a symptom of their depression, and, in turn, this withdrawal/isolation can further exacerbate the stressful experience and the depressive symptomology.

Glucocorticoids prime the inflammatory response of human hippocampal cells through up-regulation of inflammatory pathways.

Increased pro-inflammatory cytokines and an overactive hypothalamic-pituitary-adrenal (HPA) axis have both been implicated in the pathogenesis of depression. However, these explanations appear contradictory because glucocorticoids are well recognised for their anti-inflammatory effects. Two hypotheses exist to resolve this paradox: the mediating presence of glucocorticoid receptor resistance, or the possibility that glucocorticoids can potentiate inflammatory processes in some circumstances.

Schizophrenia-related dysbindin-1 gene is required for innate immune response and homeostasis in the developing subventricular zone.

Schizophrenia is a neurodevelopmental disorder likely caused by environmental and genetic risk factors but functional interactions between the risk factors are unclear. We tested the hypothesis that dysbindin-1 (Dtnbp1) gene mutation combined with postnatal exposure to viral mimetic polyI:C results in schizophrenia-related behavioural changes in adulthood, and mediates polyI:C-induced inflammation in the subventricular zone (SVZ). Adult Sandy (Sdy, Dtnbp1 mutant) mice given early postnatal polyI:C injections displayed reduced prepulse inhibition of startle, reduced locomotion and deficits in novel object recognition.

Repeated lipopolysaccharide exposure modifies immune and sickness behaviour response in an animal model of chronic inflammation.

Repeated lipopolysaccharide exposure is often used in longitudinal preclinical models of depression. However, the potential phenotypic differences from acute depression-mimicking effects are rarely described. This study compared chronic lipopolysaccharide administration of doses previously used in depression research to a new mode of escalating dose injections.

Antidepressant compounds can be both pro- and anti-inflammatory in human hippocampal cells.

Background: The increasingly recognized role of inflammation in the pathogenesis and prognosis of depression has led to a renewed focus on the immunomodulatory properties of compounds with antidepressant action. Studies have, so far, explored such properties in human blood samples and in animal models.

Methods: Here we used the more relevant model of human hippocampal progenitor cells exposed to an inflammatory milieu, induced by treatment with IL-1β.

Modulation of adult hippocampal neurogenesis by early-life environmental challenges triggering immune activation.

The immune system plays an important role in the communication between the human body and the environment, in early development as well as in adulthood. Per se, research has shown that factors such as maternal stress and nutrition as well as maternal infections can activate the immune system in the infant. A rising number of research studies have shown that activation of the immune system in early life can augment the risk of some psychiatric disorders in adulthood, such as schizophrenia and depression.

Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis.

Stress and glucocorticoid hormones regulate hippocampal neurogenesis, but the molecular mechanisms mediating these effects are poorly understood. Here we identify the glucocorticoid receptor (GR) target gene, serum- and glucocorticoid-inducible kinase 1 (SGK1), as one such mechanism. Using a human hippocampal progenitor cell line, we found that a small molecule inhibitor for SGK1, GSK650394, counteracted the cortisol-induced reduction in neurogenesis.

Glucocorticoid-related molecular signaling pathways regulating hippocampal neurogenesis.

Stress and glucocorticoid hormones regulate hippocampal neurogenesis, but the molecular mechanisms underlying their effects are unknown. We, therefore, investigated the molecular signaling pathways mediating the effects of cortisol on proliferation, neuronal differentiation, and astrogliogenesis, in an immortalized human hippocampal progenitor cell line. In addition, we examined the molecular signaling pathways activated in the hippocampus of prenatally stressed rats, characterized by persistently elevated glucocorticoid levels in adulthood.

Interleukin-1β: a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis.

Increased inflammation and reduced neurogenesis have been associated with the pathophysiology of major depression. Here, we show for the first time how IL-1β, a pro-inflammatory cytokine shown to be increased in depressed patients, decreases neurogenesis in human hippocampal progenitor cells. IL-1β was detrimental to neurogenesis, as shown by a decrease in the number of doublecortin-positive neuroblasts (-28%), and mature, microtubule-associated protein-2-positive neurons (-36%).