Early life stress differentially modulates distinct forms of brain plasticity in young and adult mice.

Background: Early life trauma is an important risk factor for many psychiatric and somatic disorders in adulthood. As a growing body of evidence suggests that brain plasticity is disturbed in affective disorders, we examined the short-term and remote effects of early life stress on different forms of brain plasticity.

Methodology/principal Findings: Mice were subjected to early deprivation by individually separating pups from their dam in the first two weeks after birth.

Early life stress stimulates hippocampal reelin gene expression in a sex-specific manner: evidence for corticosterone-mediated action.

Early life stress predisposes to the development of psychiatric disorders. In this context the hippocampal formation is of particular interest, because it is affected by stress on the structural and cognitive level. Since little is known how early life stress is translated on the molecular level, we mimicked early life stress in mouse models and analyzed the expression of the glycoprotein Reelin, a master molecule for development and differentiation of the hippocampus.

Coincidence detection and stress modulation of spike time-dependent long-term depression in the hippocampus.

Associative long-term depression (LTD) in the hippocampus is a form of spike time-dependent synaptic plasticity that is induced by the asynchronous pairing of postsynaptic action potentials and EPSPs. Although metabotropic glutamate receptors (mGluRs) and postsynaptic Ca(2+) signaling have been suggested to mediate associative LTD, mechanisms are unclear further downstream. Here we show that either mGluR1 or mGluR5 activation is necessary for LTD induction, which is therefore mediated by group I mGluRs.

Effects of substance P on memory and mood in healthy male subjects.

There is evidence from human and animal studies that substance P (SP) is involved in the etiopathology of depression and anxiety. Furthermore, animal studies have shown effects of SP on memory. In a double-blind, randomized cross-over study, 13 healthy young men received SP (1.

Substance P induces expression of the corticotropin-releasing factor receptor 1 by activation of the neurokinin-1 receptor.

The neuropeptide substance P (SP) has been found to be possibly involved in the etiology of affective and anxiety disorders. However, the molecular mechanisms underlying this involvement are still poorly understood. In this study, we used macroarrays to investigate the differential gene expression profile induced by SP, particularly of genes which have been shown to be involved in the pathophysiology of affective disorders.

No response of plasma substance P, but delayed increase of interleukin-1 receptor antagonist to acute psychosocial stress.

Psychosocial stress has been shown to induce inflammatory reactions, followed by the release of immunosuppressive glucocorticoids. This may be mediated by catecholamines or other stress reactive substances such as neuropeptides or cytokines. We here set out to explore the effects of acute psychosocial stress on plasma levels of substance P (SP), a possible mediator of stress-induced inflammatory reactions, and interleukin-1 receptor antagonist (IL-1ra).

Substance P in serum and cerebrospinal fluid of depressed patients: no effect of antidepressant treatment.

The neuropeptide substance P (SP) and its receptor, the neurokinin receptor-1 (NK-1), have been associated with some aspects of the pathophysiology of depression. There is limited information available about the effects of antidepressant treatment on serum and cerebrospinal fluid (CSF) concentrations of SP. We measured serum levels of SP in 78 depressed patients after a 6-day medication washout period, as well as after 14 and 35 days of antidepressant treatment with either paroxetine or amitriptyline.

No modulatory effect of neurokinin-1 receptor antagonists on serotonin uptake in human and rat brain synaptosomes.

Some studies have demonstrated antidepressant activity of neurokinin-1-receptor antagonists (NK-1-RA) in major depressive disorder. However, the underlying mechanisms of this antidepressant effect are largely unknown. Preclinical studies in rats and mice have suggested that NK-1-RA do increase the neuronal release of serotonin (5-HT).

A comparison of neurokinin 1 receptor knock-out (NK1-/-) and wildtype mice: exploratory behaviour and extracellular noradrenaline concentration in the cerebral cortex of anaesthetised subjects.

In behavioural screens, mice lacking functional NK1 receptors (NK1-/-) resemble wildtypes (NK1+/+) that have been given an antianxiety/antidepressant drug. Most, if not all, antidepressants increase noradrenergic transmission in the brain. Here, we have used in vivo microdialysis to compare the concentrations of extracellular noradrenaline ('efflux') in the cerebral cortex of anaesthetised NK1-/- and NK1+/+ mice.

Substance P receptor antagonists in psychiatry: rationale for development and therapeutic potential.

Increasing evidence suggests that substance P (SP) and its receptor (neurokinin [NK]-1 receptor [NK1R]) might play an important role in the modulation of stress-related, affective and/or anxious behaviour. First, SP and NK1R are expressed in brain regions that are involved in stress, fear and affective response (e.g.

Effects of substance P and its antagonist L-733060 on long term potentiation in guinea pig hippocampal slices.

The neuropeptide substance P (SP) has been suggested to be involved in several physiological and pathological conditions including learning and memory and the processing of pain. This study investigated for the first time acute effects of SP and the neurokinin-1 (NK-1) receptor antagonist L-733060 on long term potentiation (LTP) in the hippocampus. Electrically evoked fEPSP was tested under the influence of SP in the CA1 region of the guinea pig hippocampus.

Substance P and Substance P receptor antagonists in the pathogenesis and treatment of affective disorders.

Substance P (SP) is a neuropeptide which is widely distributed in the periphery and the central nervous system (CNS), where it is co-localised with other neurotransmitters such as serotonin or dopamine and where it acts as a neuromodulator. SP has been proposed to play a role in the aetiopathology of asthma, inflammatory bowel disease, emesis, psoriasis, as well as neuropsychiatric disorders including pain syndromes (e.g.

Neopterin and 7,8-dihydroneopterin interfere with low density lipoprotein oxidation mediated by peroxynitrite and/or copper.

Low density lipoprotein (LDL) oxidation within the artery wall likely represents a key event in the formation of atherosclerotic lesions. Oxidatively modified LDL particles exert chemotactic properties on macrophages, and the uncontrolled uptake of modified LDL by macrophages leads to the formation of lipid-loaded foam cells, a hallmark of early stage atherosclerosis. Human macrophages stimulated by interferon-gamma generate reactive oxygen species (ROS), neopterin, and 7,8-dihydroneopterin.