Enhanced resting-state connectivity of amygdala in the immediate aftermath of acute psychological stress.

Recent neuroimaging studies investigating responses to stressful stimuli may importantly further our understanding of psychological trauma etiology. However, theory posits that sustained activation of these stress circuits after the stressful event may play an equally important role in the development of stress-related psychopathology. Importantly, such post-stress network changes remain poorly characterized.

Acute stress modulates genotype effects on amygdala processing in humans.

Probing gene-environment interactions that affect neural processing is crucial for understanding individual differences in behavior and disease vulnerability. Here, we tested whether the current environmental context, which affects the acute brain state, modulates genotype effects on brain function in humans. We manipulated the context by inducing acute psychological stress, which increases noradrenergic activity, and probed its effect on tonic activity and phasic responses in the amygdala using two MRI techniques: conventional blood oxygen level-dependent functional MRI and arterial spin labeling.

Effects of exogenous testosterone on the ventral striatal BOLD response during reward anticipation in healthy women.

Correlational evidence in humans shows that levels of the androgen hormone testosterone are positively related to reinforcement sensitivity and competitive drive. Structurally similar anabolic-androgenic steroids (AAS) are moreover widely abused, and animal studies show that rodents self-administer testosterone. These observations suggest that testosterone exerts activational effects on mesolimbic dopaminergic pathways involved in incentive processing and reinforcement regulation.

Persistent schema-dependent hippocampal-neocortical connectivity during memory encoding and postencoding rest in humans.

The hippocampus is thought to promote gradual incorporation of novel information into long-term memory by binding, reactivating, and strengthening distributed cortical-cortical connections. Recent studies implicate a key role in this process for hippocampally driven crosstalk with the (ventro)medial prefrontal cortex (vmPFC), which is proposed to become a central node in such representational networks over time. The existence of a relevant prior associative network, or schema, may moreover facilitate this process.

Functionally selective cannabinoid receptor signalling: therapeutic implications and opportunities.

The CB(1) and CB(2) cannabinoid receptors are G protein-coupled receptors (GPCRs) recognized by a variety of endogenous ligands and activating multiple signalling pathways. This multiplicity of ligands and intracellular transduction mechanisms supports a complex control of physiological functions by the endocannabinoid system, but requires a finely tuned regulation of the signalling events triggered on receptor activation. Here we review the diverse signalling pathways activated by the cannabinoid receptors and discuss the mechanisms allowing for specificity in the associated functional responses triggered by endogenous or exogenous ligands.

Cortisol administration acutely reduces threat-selective spatial attention in healthy young men.

There is mounting evidence that single administrations of glucocorticoids may acutely reduce human fear. We previously reported that administration of cortisol acutely reduced non-spatial selective attention to fearful faces and likewise reduced preferential processing of fearful faces in a spatial working memory task. Here we report the acute effects of 40 mg cortisol (administered in a double-blind, placebo-controlled crossover design) on a different experimental task for measuring threat-selective attention.

Testosterone administration modulates neural responses to crying infants in young females.

Parental responsiveness to infant vocalizations is an essential mechanism to ensure parental care, and its importance is reflected in a specific neural substrate, the thalamocingulate circuit, which evolved through mammalian evolution subserving this responsiveness. Recent studies using functional Magnetic Resonance Imaging (fMRI) provide compelling evidence for a comparable mechanism in humans by showing thalamocingulate responses to infant crying. Furthermore, possibly acting on this common neural substrate, steroid hormones such as estradiol and testosterone, seem to mediate parental behavior both in humans and other animals.

Neural mechanisms underlying changes in stress-sensitivity across the menstrual cycle.

Hormonal fluctuations across the menstrual cycle are thought to play a central role in premenstrual mood symptoms. In agreement, fluctuations in gonadal hormone levels affect brain processes in regions involved in emotion regulation. Recent findings, however, implicate psychological stress as a potential mediating factor and thus, we investigated whether effects of moderate psychological stress on relevant brain regions interact with menstrual cycle phase.

Stressed memories: how acute stress affects memory formation in humans.

Stressful, aversive events are extremely well remembered. Such a declarative memory enhancement is evidently beneficial for survival, but the same mechanism may become maladaptive and culminate in mental diseases such as posttraumatic stress disorder (PTSD). Stress hormones are known to enhance postlearning consolidation of aversive memories but are also thought to have immediate effects on attentional, sensory, and mnemonic processes at memory formation.

From specificity to sensitivity: how acute stress affects amygdala processing of biologically salient stimuli.

Background: A vital component of an organism's response to acute stress is a surge in vigilance that serves to optimize the detection and assessment of threats to its homeostasis. The amygdala is thought to regulate this process, but in humans, acute stress and amygdala function have up to now only been studied in isolation. Hence, we developed an integrated design using functional magnetic resonance imaging to investigate the immediate effects of controlled stress induction on amygdala function.

Distinct expression and regulation of the glutamate transporter isoforms GLT-1a and GLT-1b in cultured astrocytes from a rat model of amyotrophic lateral sclerosis (hSOD1G93A).

Impaired glutamate uptake associated with accumulation of extracellular glutamate is a well-documented feature of amyotrophic lateral sclerosis (ALS) and related excitotoxicity is frequently proposed to participate in the progression of the disease. We herein characterised the expression and activity of the glutamate transporter glutamate transporter 1 (GLT-1) in cultured cortical astrocytes derived from a transgenic rat strain expressing an ALS-related mutated form of human superoxide dismutase 1 (hSOD1(G93A)). Measurements of d-[(3)H]-aspartate uptake velocity in the presence of selective glutamate transporter blockers demonstrated that astrocytes from the transgenic rats showed an impaired GLT-1 activity as compared to cells from wild-type animals.

Acute psychological stress reduces working memory-related activity in the dorsolateral prefrontal cortex.

Background: Acute psychological stress impairs higher-order cognitive function such as working memory (WM). Similar impairments are seen in various psychiatric disorders that are associated with higher susceptibility to stress and with prefrontal cortical dysfunctions, suggesting that acute stress may play a potential role in such dysfunctions. However, it remains unknown whether acute stress has immediate effects on WM-related prefrontal activity.

Enhanced expression of the high affinity glutamate transporter GLT-1 in C6 glioma cells delays tumour progression in rat.

High grade gliomas are known to release excitotoxic concentrations of glutamate, a process thought to contribute to their malignant phenotype through enhanced autocrine stimulation of their proliferation and destruction of the surrounding nervous tissue. A model of C6 glioma cells in which expression of the high affinity glutamate transporter GLT-1 can be manipulated both in vivo and in vitro was used in order to investigate the consequences of increasing glutamate clearance on tumour progression. These cells were grafted in the striatum of Wistar rats and doxycycline was administered after validation of tumour development by magnetic resonance imaging.

Dissecting medial temporal lobe contributions to item and associative memory formation.

A fundamental and intensively discussed question is whether medial temporal lobe (MTL) processes that lead to non-associative item memories differ in their anatomical substrate from processes underlying associative memory formation. Using event-related functional magnetic resonance imaging, we implemented a novel design to dissociate brain activity related to item and associative memory formation not only by subsequent memory performance and anatomy but also in time, because the two constituents of each pair to be memorized were presented sequentially with an intra-pair delay of several seconds. Furthermore, the design enabled us to reduce potential differences in memory strength between item and associative memory by increasing task difficulty in the item recognition memory test.

Chimerization of astroglial population in the lumbar spinal cord after mesenchymal stem cell transplantation prolongs survival in a rat model of amyotrophic lateral sclerosis.

Adult mesenchymal stem cells (MSCs) exhibit neuroprotective properties when introduced into the degenerating central nervous system through different putative mechanisms including secretion of growth factors and transdifferentiation. In the present study, we injected MSCs into the cerebrospinal fluid of symptomatic hSOD1(G93A) rats, a transgenic animal model of familial amyotrophic lateral sclerosis (ALS) expressing a mutated form of the human superoxide dismutase. MSCs were found to infiltrate the nervous parenchyma and migrate substantially into the ventral gray matter, where motor neurons degenerate.

Cultured astrocytes derived from corpus callosum or cortical grey matter show distinct glutamate handling properties.

While the astrocytic control of extracellular glutamate concentration at synaptic contacts is well characterized, little is known regarding the clearance of glutamate along axon tracts, even though local excitotoxic damage has been reported. Therefore, we have compared glutamate handling in astrocyte cultures derived from white matter (corpus callosum) and grey matter tissues (cortical structures). These populations of astrocytes showed clearly distinct phenotypes, adopting stellate or protoplasmic morphologies respectively.

Gray's BIS/BAS dimensions in non-comorbid, non-medicated social anxiety disorder.

Gray's behavioural inhibition and behavioural activation (BIS/BAS) neural systems model has led to research on approach and withdrawal as the two most fundamental dimensions of affective behaviour, and their role in psychopathology. Although Gray proposed the BIS as the neurological basis of anxiety, there are no reports examining approach and withdrawal predispositions in social anxiety disorder. Here we report approach and withdrawal predispositions in a group of 23 non-medicated individuals with social anxiety disorder (SAD) without co-morbid depression and in 48 normal controls.

Reduced spontaneous facial mimicry in women with autistic traits.

Deficits in empathizing and perspective taking are defining characteristics of autism-spectrum disorders. Converging evidence suggests that these socio-emotional abilities are rooted in basic mechanisms that subserve imitative behavior, and may vary with autistic traits across the population as a whole. We investigated this notion by assessing spontaneous and instructed mimicry of facial expressions in healthy male and female volunteers scoring extremely high or low on the autism-spectrum quotient questionnaire.

Multiplicity and regulation of G-protein couplings.

During the last twenty years, molecular and biochemical data concerning G-protein coupled receptors have accumulated, providing a detailed characterisation of the structure and functions of this large family of receptors. Initially viewed as simple transducing proteins interacting with intracellular adapters which confer signalling specificity and amplification, the last decade has revealed the extreme complexity and flexibility offered by these membrane receptors. Indeed, there is accumulating evidence that these receptors can interact with several unrelated G-proteins and that some ligands can specifically orientate the functional response.

Adult stem cell therapies for neurological disorders: benefits beyond neuronal replacement?

The modest capacity of endogenous repair processes in the central nervous system (CNS) justifies the broad interest in the development of effective stem cell based therapies for neurodegenerative disorders and other acute or chronic lesions. Motivated by the ambitious expectation to achieve functional neuronal replacement, several studies have already evidenced a potential benefit of stem cell grafts in animal models of human disorders. Nevertheless, growing evidence suggests that the effects orchestrated by stem cells, in most experimental cases, are not necessarily associated with the generation of new neurons.

Benchmarking road safety: lessons to learn from a data envelopment analysis.

Road safety performance indicators (SPI) have recently been proposed as a useful instrument in comparing countries on the performance of different risk aspects of their road safety system. In this respect, SPIs should be actionable, i.e.

Equivalent refractive index of the human lens upon accommodative response.

Purpose: To experimentally verify the suggestion of Gullstrand (1909), i.e., that the equivalent refractive index of the human lens increases with accommodation.

Development of a ciliary muscle-driven accommodating intraocular lens.

Purpose: To develop a ciliary muscle-driven accommodating intraocular lens (IOL) that has a large and predictable range of variable power as a step toward spectacle independence.

Setting: Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands.

Methods: A concept IOL that has a rotating focus mechanism and a mechanical frame that can operate within the range of ciliary muscle contraction of a typical 60-year-old human eye was designed.

Concomitant activation of adenylyl cyclase suppresses the opposite influences of CB(1) cannabinoid receptor agonists on tyrosine hydroxylase expression.

The CB(1) cannabinoid receptor shows complex interactions with intracellular signalling partners, and responses to cannabinoid ligands are likely to be influenced by concomitant inputs modifying the overall tone of signalling cascades. This appears even more relevant as we previously evidenced opposite regulations of tyrosine hydroxylase (TH) expression by the two common cannabinoid agonists HU 210 and CP 55,940. Therefore, we studied the consequences of manipulating adenylyl cyclase activity with forskolin on the regulation of TH gene transcription in neuroblastoma cells (N1E-115).