Long-term course of brain-derived neurotrophic factor serum levels in a patient treated with deep brain stimulation of the lateral habenula.

Introduction: According to the neurotrophin hypothesis, a brain-derived neurotrophic factor (BDNF) decrease has been postulated as a pivotal pathomechanism in affective disorder, and the treatment-associated increase in peripheral BDNF has been linked to therapeutic efficacy of antidepressant drugs and electroconvulsive therapy. However, in deep brain stimulation (DBS), a still experimental antidepressant treatment approach, this issue has not yet been investigated.

Methods: We examine the long-term course of serum BDNF levels in a 64-year-old woman who is being treated with DBS of the lateral habenula for severe major depressive disorder.

The mGlu5 receptor antagonist MPEP activates specific stress-related brain regions and lacks neurotoxic effects of the NMDA receptor antagonist MK-801: significance for the use as anxiolytic/antidepressant drug.

Glutamatergic agents have been conceptualized as powerful, fast-acting alternatives to monoaminergic-based antidepressants. NMDA receptor antagonists such as ketamine or MK-801 are therapeutically effective, but their clinical use is hampered by psychotomimetic effects, accompanied by neurotoxicity in the retrosplenial and cingulate cortex. Antagonists of metabotropic mGlu5 receptors like MPEP elicit both robust antidepressant and anxiolytic effects; however, the underlying mechanisms are yet unknown.

Pramipexole is active in depression tests and modulates monoaminergic transmission, but not brain levels of BDNF in mice.

The dopamine D(2)/D(3) receptor agonist pramipexole exerts antidepressive capacities in patients with Parkinson's disease with little evidence for patients with affective diseases only. Little is known about the neurobiological basis of these antidepressive effects. In this study, C57BL/6N mice received acute or chronic (3 weeks) treatment with pramipexole in different dosages (0.

Sensorimotor gating, working and social memory deficits in mice with reduced expression of the vesicular glutamate transporter VGLUT1.

Glutamate is the main excitatory neurotransmitter in the central nervous system. A hypoglutamatergic state is believed to play an important role in the pathophysiology of schizophrenia. The release of glutamate in the brain is modulated by a class of vesicular glutamate transporters, VGLUT1-3.

Inherited and de novo SHANK2 variants associated with autism spectrum disorder impair neuronal morphogenesis and physiology.

Mutations in the postsynaptic scaffolding gene SHANK2 have recently been identified in individuals with autism spectrum disorder (ASD) and intellectual disability. However, the cellular and physiological consequences of these mutations in neurons remain unknown. We have analyzed the functional impact caused by two inherited and one de novo SHANK2 mutations from ASD individuals (L1008_P1009dup, T1127M, R462X).

Stress worsens endothelial function and ischemic stroke via glucocorticoids.

Background And Purpose: Chronic stress is associated with increased stroke risk. However, the underlying pathophysiological mechanisms are poorly understood. We examined the effects of chronic stress on endothelial function and ischemic brain injury in a mouse model.

Mediating effects of stalking victimization on gender differences in mental health.

Studies suggest that stalking victimization may have a serious mental health impact. The present article investigates gender differences in mental health and possible mediating effects of stalking victimization in a community sample. The study includes a postal survey of 665 German community residents on the experience of stalking and various mental health indicators.

Increase of hippocampal glutamate after electroconvulsive treatment: a quantitative proton MR spectroscopy study at 9.4 T in an animal model of depression.

Objectives: Recent evidence suggests that alterations in hippocampal glutamate and γ-aminobutyric acid (GABA) are associated with the pathomechanism of depression and treatment effects of electroconvulsive therapy (ECT). Thus, proton magnetic resonance spectroscopy (¹H MRS) at a 9.4 T animal system seems a promising tool to study underlying mechanisms since it allows for an accurate quantification of metabolites with distinction of glutamate, GABA and glutamine, as well as separation of taurine from choline.

Voluntary exercise does not ameliorate context memory and hyperarousal in a mouse model for post-traumatic stress disorder (PTSD).

Objectives: We investigated the effects of voluntary wheel running as model for intervention on the development of contextual fear and hyperarousal in a mouse model of post-traumatic stress disorder (PTSD). Physical exercise in general has been associated with improved hippocampus-dependent memory performance both in animals and humans. However, studies that have tried to link physical exercise and contextual conditioning in an animal model of PTSD, revealed mixed findings.

Are stalkers disordered or criminal? Thoughts on the psychopathology of stalking.

Although stalking is a widespread phenomenon that can be caused by different motives, consideration of the psychopathological underpinnings of stalking behaviour is scarce. In rare cases, stalking can be an expression of mental disorder. Psychotic stalking, for example, can occur as a symptom of schizophrenia or erotomania.

Chronic isolation stress predisposes the frontal cortex but not the hippocampus to the potentially detrimental release of cytochrome c from mitochondria and the activation of caspase-3.

Mitochondria are central integrators and transducers of proapoptotic signals for neuronal apoptosis. The tumor suppressor protein p53 can trigger apoptosis independently of its transcriptional activity, through subcellular translocation of cytochrome c and caspase activation. To define better the proapoptotic role of p53 under various stress conditions, we investigated the protein levels of p53 and cytochrome c in mitochondrial and cytosolic fractions, as well as caspase-3 activation and apoptosis, in the prefrontal cortex and hippocampus of male Wistar rats subjected to acute, chronic, or combined stressors.

Pten ablation in adult dopaminergic neurons is neuroprotective in Parkinson's disease models.

Parkinson's disease (PD) is a progressive age-related movement disorder that results primarily from the selective loss of midbrain dopaminergic (DA) neurons. Symptoms of PD can be induced by genetic mutations or by DA neuron-specific toxins. A specific ablation of an essential factor controlling ribosomal RNA transcription, TifIa, in adult mouse DA neurons represses mTOR signaling and leads to progressive neurodegeneration and PD-like phenotype.

Differences in mouse maternal care behavior - is there a genetic impact of the glucocorticoid receptor?

Depressive episodes are frequently preceded by stressful life events. Evidence from genetic association studies suggests a role for the glucocorticoid receptor (GR), an essential element in the regulation of stress responses, in the pathophysiology of the disorder. Since the stress response system is affected by pregnancy and postpartum-associated changes, it has also been implicated in the pathophysiology of postpartum depression.

APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP.

Despite its key role in Alzheimer pathogenesis, the physiological function(s) of the amyloid precursor protein (APP) and its proteolytic fragments are still poorly understood. Previously, we generated APPsα knock-in (KI) mice expressing solely the secreted ectodomain APPsα. Here, we generated double mutants (APPsα-DM) by crossing APPsα-KI mice onto an APLP2-deficient background and show that APPsα rescues the postnatal lethality of the majority of APP/APLP2 double knockout mice.

Effects of chronic oral treatment with aripiprazole on the expression of NMDA receptor subunits and binding sites in rat brain.

Rationale: The glutamatergic theory of schizophrenia proposes a dysfunction of ionotropic N-methyl-D: -aspartate receptors (NMDA-R). Several therapeutic strategies address NMDA-R function and the effects of antipsychotic agents on NMDA-R expression have been described. Within the second-generation antipsychotics, the partial dopaminergic and serotonergic agonist aripiprazole (APZ) was able to counteract the behavioral effects of NMDA-R antagonists.

Lack of long-term behavioral alterations after early postnatal treatment with tropisetron: implications for developmental psychobiology.

The early postnatal period represents a critical time window for brain development. Transient Cajal-Retzius cells in layer I of the cortex play an important role in cortical lamination by modulating neuronal migration and maturation. Recent data have demonstrated that the 5-HT(3) receptor antagonist and alpha7 nicotinic receptor partial agonist tropisetron, acting via 5-HT(3) receptors expressed on Cajal-Retzius cells, can disturb the formation of cortical columns at perinatal stages.

Effect of population heterogenization on the reproducibility of mouse behavior: a multi-laboratory study.

In animal experiments, animals, husbandry and test procedures are traditionally standardized to maximize test sensitivity and minimize animal use, assuming that this will also guarantee reproducibility. However, by reducing within-experiment variation, standardization may limit inference to the specific experimental conditions. Indeed, we have recently shown in mice that standardization may generate spurious results in behavioral tests, accounting for poor reproducibility, and that this can be avoided by population heterogenization through systematic variation of experimental conditions.

Synaptoproteomics of learned helpless rats involve energy metabolism and cellular remodeling pathways in depressive-like behavior and antidepressant response.

Although depression is a severe and life-threatening psychiatric illness, its pathogenesis still is essentially unknown. Recent studies highlighted the influence of environmental stress factors on an individual's genetic predisposition to develop mood disorders. In the present study, we employed a well-validated stress-induced animal model of depression, Learned Helplessness paradigm, in rats.

Finasteride-induced depression: new insights into possible pathomechanisms.

5-alpha-reductase is involved as a rate-imitating enzyme in the metabolism of steroids. Several 5-alpha-reduced steroids such as dihydrotestosterone, allopregnanolone or tetrahydrocorticosterone have neurotrophic, neuroprotective, and anxiolytic properties. Reduced 5-alpha-reductase activity has been observed during depressive illness in humans.

[The role of the glutamatergic system in pathophysiology and pharmacotherapy for depression: preclinical and clinical data].

An increasing significance has been attributed to the glutamatergic system in the pathophysiology of affective disorders. Glutamate is the most important excitatory neurotransmitter in the central nervous system. Glia cells are crucial regulators of the glutamatergic metabolism.

Alterations in postnatal neurogenesis and dopamine dysregulation in schizophrenia: a hypothesis.

An increasing number of studies demonstrate the important role of several susceptibility genes for schizophrenia, such as neuregulin-1 and DISC1, in early postnatal and adult neurogenesis. Its significance for the pathophysiology of the disease, including its relation to neurotransmitter systems implicated in schizophrenia (like the dopamine system), remains, however, unknown. Here, we review molecular and cellular components of the dopamine system associated with postnatal neurogenesis and plasticity, both in rodents and in primates, and discuss their possible implication in schizophrenia.

Deletion of running-induced hippocampal neurogenesis by irradiation prevents development of an anxious phenotype in mice.

Recent evidence postulates a role of hippocampal neurogenesis in anxiety behavior. Here we report that elevated levels of neurogenesis elicit increased anxiety in rodents. Mice performing voluntary wheel running displayed both highly elevated levels of neurogenesis and increased anxiety in three different anxiety-like paradigms: the open field, elevated O-maze, and dark-light box.

The puzzle box as a simple and efficient behavioral test for exploring impairments of general cognition and executive functions in mouse models of schizophrenia.

Deficits in executive functions are key features of schizophrenia. Rodent behavioral paradigms used so far to find animal correlates of such deficits require extensive effort and time. The puzzle box is a problem-solving test in which mice are required to complete escape tasks of increasing difficulty within a limited amount of time.

Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder?

Glutamatergic dysfunction is strongly implicated in schizophrenia and mood disorders. GluA1 knockout (KO) mice display schizophrenia- and depression-related abnormalities. Here, we asked whether GluA1 KO show mania-related abnormalities.

Prevalence of stalking in a psychiatric hospital population.

Objective: Study of the lifetime prevalence of stalking and types of stalking in a sample of psychiatric inpatients.

Methods: A total of 300 patients consecutively admitted to the psychiatric hospital of the Central Institute of Mental Health (Zentralinstitut für Seelische Gesundheit) in Mannheim were studied by means of the Stalking Behaviour Questionnaire (Stalking-Verhaltens-Fragebogen).

Results: Of the sample, 21% at some time in their lives had been the victim of stalking.