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.

Inflammatory biomarker profiles of mental disorders and their relation to clinical, social and lifestyle factors.

In the last few decades, mental health research has increasingly provided evidence supporting the role of inflammation in pathogenesis, course and treatment of mental disorders. With such a steep incline of research, resulting in a wealth of emerged findings, it has become difficult to follow developments within the field. The present review sets out to present the recent developments and to give an overview of the inflammatory profiles of depression, psychosis and bipolar disorder, as well as variations within these disorders.

The Interface of Stress and the HPA Axis in Behavioural Phenotypes of Mental Illness.

Abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function are one of the most consistent biological findings across several mental disorders, but many of the mechanisms underlying this abnormality as well as the potential contribution to behavioural phenotypes remain only partially understood. Interestingly, evidence suggests a U-curve, with dysregulation of the HPA axis towards both hyper- or hypoactivity manifesting as a risk to mental wellbeing. This review will elaborate on both the clinical and molecular role of the neuroendocrine stress system in depressive, psychotic and post-traumatic stress disorders and present some of the most recent findings that have shed light on the complex interface between environmental stressors, molecular mechanisms and clinical presentation.

Depression during pregnancy: molecular regulations of mothers' and children's behaviour.

Depression in pregnancy (also called 'antenatal depression') is being increasingly recognized as a clinically relevant condition that affects obstetric outcome, maternal behaviour and children's future mental health. The present review focuses on the molecular mechanisms operating in utero that underlie the potential effects of antenatal depression on mothers' and children's behaviour. In particular, I discuss evidence, coming largely from animal and cellular studies, that activation of the main hormonal stress-response system, the HPA (hypothalamic-pituitary-adrenal) axis, in mothers who are depressed during pregnancy may affect maternal care as well as offspring's behaviour and future psychopathology.

The imbalanced redox status in senescent endothelial cells is due to dysregulated Thioredoxin-1 and NADPH oxidase 4.

Environmental stressors as well as genetic modifications are known to enhance oxidative stress and aging processes. Mitochondrial and nuclear dysfunctions contribute to the onset of aging. One of the most important redox regulators in primary human endothelial cells is Thioredoxin-1 (Trx-1), a 12 kD protein with additional anti-apoptotic properties.

Coordinated nuclear and synaptic shuttling of afadin promotes spine plasticity and histone modifications.

The ability of a neuron to transduce extracellular signals into long lasting changes in neuronal morphology is central to its normal function. Increasing evidence shows that coordinated regulation of synaptic and nuclear signaling in response to NMDA receptor activation is crucial for long term memory, synaptic tagging, and epigenetic signaling. Although mechanisms have been proposed for synapse-to-nuclear communication, it is unclear how signaling is coordinated at both subcompartments.

Consequences of cancer treatments on adult hippocampal neurogenesis: implications for cognitive function and depressive symptoms.

The human brain is capable of generating new functional neurons throughout life, a phenomenon known as adult neurogenesis. The generation of new neurons is sustained throughout adulthood due to the proliferation and differentiation of adult neural stem cells. This process in humans is uniquely located in the subgranular zone of the dentate gyrus in the hippocampus.

Reduced cortical volume and elevated astrocyte density in rats chronically treated with antipsychotic drugs-linking magnetic resonance imaging findings to cellular pathology.

Background: Increasing evidence suggests that antipsychotic drugs (APD) might affect brain structure directly, particularly the cerebral cortex. However, the precise anatomical loci of these effects and their underlying cellular basis remain unclear.

Methods: With ex vivo magnetic resonance imaging in rats treated chronically with APDs, we used automated analysis techniques to map the regions that show maximal impact of chronic (8 weeks) treatment with either haloperidol or olanzapine on the rat cortex.

Insights into rapid modulation of neuroplasticity by brain estrogens.

Converging evidence from cellular, electrophysiological, anatomic, and behavioral studies suggests that the remodeling of synapse structure and function is a critical component of cognition. This modulation of neuroplasticity can be achieved through the actions of numerous extracellular signals. Moreover, it is thought that it is the integration of different extracellular signals regulation of neuroplasticity that greatly influences cognitive function.

The utility of patient specific induced pluripotent stem cells for the modelling of Autistic Spectrum Disorders.

Until now, models of psychiatric diseases have typically been animal models. Whether they were to be used to further understand the pathophysiology of the disorder, or as drug discovery tools, animal models have been the choice of preference in mimicking psychiatric disorders in an experimental setting. While there have been cellular models, they have generally been lacking in validity.

G-protein oestrogen receptor 1: trials and tribulations of a membrane oestrogen receptor.

Oestrogens are now recognised to be able to initiate rapid, fast responses, in addition to their classical, longer-term actions. There is a growing appreciation of the potential implications of this mode of action for oestrogenic signalling in both neuronal and non-neuronal systems. As such, much effort has been made to determine the mechanisms that are critical for transducing these rapid effects into cellular responses.

Role of oxidants on calcium and sodium movement in healthy and diseased cardiac myocytes.

In this review article we give an overview of current knowledge with respect to redox-sensitive alterations in Na(+) and Ca(2+) handling in the heart. In particular, we focus on redox-activated protein kinases including cAMP-dependent protein kinase A (PKA), protein kinase C (PKC), and Ca/calmodulin-dependent protein kinase II (CaMKII), as well as on redox-regulated downstream targets such as Na(+) and Ca(2+) transporters and channels. We highlight the pathological and physiological relevance of reactive oxygen species and some of its sources (such as NADPH oxidases, NOXes) for excitation-contraction coupling (ECC).

Nox2 is required for macrophage chemotaxis towards CSF-1.

Macrophage migration and infiltration is an important first step in many pathophysiological processes, in particular inflammatory diseases. Redox modulation of the migratory signalling processes has been reported in endothelial cells, vascular smooth muscle cells and fibroblasts. However the redox modulation of the migratory process in macrophages and in particular that from the NADPH oxidase-2 (Nox2) dependent ROS has not been established.

Mechanisms underlying the interactions between rapid estrogenic and BDNF control of synaptic connectivity.

The effects of the steroid hormone 17β-estradiol and the neurotrophin brain-derived neurotrophic factor (BDNF) on neuronal physiology have been well investigated. Numerous studies have demonstrated that each signal can exert powerful influences on the structure and function of synapses, and specifically on dendritic spines, both within short and long time frames. Moreover, it has been suggested that BDNF is required for the long-term, or genomic, actions of 17β-estradiol on dendritic spines, via its ability to regulate the expression of neurotrophins.

Human neural progenitor cell engraftment increases neurogenesis and microglial recruitment in the brain of rats with stroke.

Main Objectives: Stem cell transplantation is to date one of the most promising therapies for chronic ischemic stroke. The human conditionally immortalised neural stem cell line, CTX0E03, has demonstrable efficacy in a rodent model of stroke and is currently in clinical trials. Nonetheless, the mechanisms by which it promotes brain repair are not fully characterised.

Nutrition, adult hippocampal neurogenesis and mental health.

Introduction: Over the last 8 years, emerging studies bridging the gap between nutrition and mental health have resolutely established that learning and memory abilities as well as mood can be influenced by diet. However, the mechanisms by which diet modulates mental health are still not well understood. Sources of data In this article, a review of the literature was conducted using PubMed to identify studies that provide functional implications of adult hippocampal neurogenesis (AHN) and its modulation by diet.

Epigenetics in vascular disease - therapeutic potential of new agents.

Vascular diseases, including atherosclerosis, angioplasty-induced restenosis, vessel graft arteriosclerosis and hypertension-related stenosis, remain the most prevalent cause of death in the developed world. The aetiology of vascular diseases is multifactorial with both genetic and environmental factors. Recently, some of the most promising research identifies the epigenetic modification of the genome to play a major role in the disease development, linking the environmental insults with gene regulation.

Two-step wiring plasticity--a mechanism for estrogen-induced rewiring of cortical circuits.

Estrogens have been shown to exert powerful effects on cognitive behaviors mediated by several areas of the brain including the cortex. Remodeling of spiny synapses is a key step in the rewiring of neuronal circuitry thought to underlie the processing and storage of information in the forebrain. Whereas estrogen has been shown to regulate synapse structure and function, we are only just starting to understand the molecular and cellular underpinnings of how estrogens can modulate neuronal circuits.

Repressor element 1 silencing transcription factor couples loss of pluripotency with neural induction and neural differentiation.

Neural differentiation of embryonic stem cells (ESCs) requires coordinated repression of the pluripotency regulatory program and reciprocal activation of the neurogenic regulatory program. Upon neural induction, ESCs rapidly repress expression of pluripotency genes followed by staged activation of neural progenitor and differentiated neuronal and glial genes. The transcriptional factors that underlie maintenance of pluripotency are partially characterized whereas those underlying neural induction are much less explored, and the factors that coordinate these two developmental programs are completely unknown.

REST: transcriptional and epigenetic regulator.

Acquisition and maintenance of cell fate and potential are dependent on the complex interplay of extracellular signaling, gene regulatory networks and epigenetic states. During embryonic development, embryonic stem cells become progressively more restricted along specific lineages, ultimately giving rise to the diversity of cell types in the adult mammalian organism. Recent years have seen major advances in our understanding of the mechanisms that regulate the underlying transcriptional programmes during development.

Selective activation of metabotropic glutamate receptor 7 induces inhibition of cellular proliferation and promotes astrocyte differentiation of ventral mesencephalon human neural stem/progenitor cells.

Expression of group III metabotropic glutamate receptors (mGluR) was established by RT-PCR and immunocytochemistry on a cultured clonal human neural stem/progenitor cell (hNSPC) line derived from fetal ventral mesencephalon (VM). Selective activation of these receptors by the group III mGluR agonist L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) prevented increases in cAMP levels following forskolin stimulation, suggesting these receptors are coupled to their canonical G-protein coupled signal transduction pathway. Tonic exposure of undifferentiated cultures to L-AP4 resulted in a decrease in cellular metabolism and proliferation in the absence of toxicity, as measured by MTT and LDH assays, in a dose-dependent manner.

Non-invasive MR imaging of neurodegeneration in a rodent model of Parkinson's disease.

Neurotoxin-based rodent models of Parkinson's disease (PD) are widely used for pre-clinical evaluation of novel therapeutics for PD and have provided insights into mechanisms underlying motor dysfunction and nigrostriatal degeneration in PD. Predominantly, magnetic resonance imaging (MRI) studies in such models have focused on alterations in T(2) water (1)H relaxation or (1)H MR spectroscopy (MRS), whilst potential morphological changes and their relationship to histological or behavioural outcomes have not been fully investigated. Identification of MR signal changes that are significantly related to behavioural and histological outcomes in pre-clinical PD models may identify useful non-invasive surrogate markers of nigrostriatal degeneration in vivo.

From molecules to man: the dawn of a vitreous man.

One of the greatest challenges to study the structure, function, and molecules in the living brain is that it is enclosed within the skull and difficult to access. Although biopsies are feasible, they are invasive, could lead to functional impairments, and in any case will only provide a small regional sample that is not necessarily reflecting the entire brain. Since the beginning of the twentieth century, in vivo imaging has gradually, and steadily, matured into non-invasive techniques that enable the repeated investigation of the structural, functional, cellular, and molecular composition of the brain.

Rescue of gene expression by modified REST decoy oligonucleotides in a cellular model of Huntington's disease.

Transcriptional dysfunction is a prominent hallmark of Huntington's disease (HD). Several transcription factors have been implicated in the aetiology of HD progression and one of the most prominent is repressor element 1 (RE1) silencing transcription factor (REST). REST is a global repressor of neuronal gene expression and in the presence of mutant Huntingtin increased nuclear REST levels lead to elevated RE1 occupancy and a concomitant increase in target gene repression, including brain-derived neurotrophic factor.