rudyvdbrink/CitationDatabase huggingface dataset:
POMC and NPY mRNA expression during development is increased in rat offspring brain from mothers fed with a high fat diet.
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2018

Developmental programing is influenced by perinatal nutrition and it has long-lasting impacts on adult metabolism in the offspring. In particular, maternal high fat diet has been associated with increased risk of obesity and metabolic disorders during adulthood in the descendants. These effects may be due to the effects of the high fat diet on the development of the systems that regulate food intake and energy balance in the offspring hypothalamus. The arcuate nucleus (ARC) may be a particularly sensitive region to it as this nucleus contains the POMC and AgRP/NPY neurons that integrate the melanocortin system. Thus, the aim of this study was to investigate the effects of maternal high fat diet during pregnancy on the transcription factors that regulate hypothalamic development in the offspring as a potential mechanism that may result in altered neuronal expression of POMC, NPY and/or AgRP. To this end, pregnant females exposed to high fat diet (60% fat diet since day 0 of pregnancy) or standard rat chow were sacrificed on days 12, 14, 16 and 18 of gestation to obtain brains from their developing fetuses and examine the mRNA expression of transcription factors associated with the development of cells in the ARC. Results show that, while no changes in transcription factor expression between groups were observed, POMC and NPY mRNA expression were higher on embryonic day 18 in the high fat group. These results suggest that POMC and NPY expression are altered by in utero exposure to a high fat diet, but these changes in gene expression are not associated with changes in the expression of transcription factors known to determine the fate of ARC cells.
β-Secretase BACE1 Promotes Surface Expression and Function of Kv3.4 at Hippocampal Mossy Fiber Synapses.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018

The β-secretase β-site APP-cleaving enzyme 1 (BACE1) is deemed a major culprit in Alzheimer's disease, but accumulating evidence indicates that there is more to the enzyme than driving the amyloidogenic processing of the amyloid precursor protein. For example, BACE1 has emerged as an important regulator of neuronal activity through proteolytic and, most unexpectedly, also through nonproteolytic interactions with several ion channels. Here, we identify and characterize the voltage-gated K
Glial origin of mesenchymal stem cells in a tooth model system.
Nature, 2014

Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells form mesenchymal stem cells in most tissues. The continuously growing mouse incisor tooth offers an excellent model to address the origin of mesenchymal stem cells. These stem cells dwell in a niche at the tooth apex where they produce a variety of differentiated derivatives. Cells constituting the tooth are mostly derived from two embryonic sources: neural crest ectomesenchyme and ectodermal epithelium. It has been thought for decades that the dental mesenchymal stem cells giving rise to pulp cells and odontoblasts derive from neural crest cells after their migration in the early head and formation of ectomesenchymal tissue. Here we show that a significant population of mesenchymal stem cells during development, self-renewal and repair of a tooth are derived from peripheral nerve-associated glia. Glial cells generate multipotent mesenchymal stem cells that produce pulp cells and odontoblasts. By combining a clonal colour-coding technique with tracing of peripheral glia, we provide new insights into the dynamics of tooth organogenesis and growth.
A Division 18 conversation with the new APA Chief Executive Officer (CEO): Arthur C. Evans, PhD.
Psychological services, 2020

The new Chief Executive Officer of the American Psychological Association (APA) Arthur C. Evans, Jr., Ph.D., has a long-standing career in public service and an ongoing commitment to public service psychology. Leadership of APA Division 18 (Psychologists in Public Service) recently interviewed Dr. Evans about his position at APA and his vision for public service psychology and its role in the U.S. health care system. Issues for discussion were selected by the Division's sections on community and state hospitals; criminal justice; police and public safety; psychologists in Indian country; serious mental illness/severe emotional disturbance; students; and veterans affairs. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Reduction of thalamic and cortical Ih by deletion of TRIP8b produces a mouse model of human absence epilepsy.
Neurobiology of disease, 2016

Absence seizures occur in several types of human epilepsy and result from widespread, synchronous feedback between the cortex and thalamus that produces brief episodes of loss of consciousness. Genetic rodent models have been invaluable for investigating the pathophysiological basis of these seizures. Here, we identify tetratricopeptide-containing Rab8b-interacting protein (TRIP8b) knockout mice as a new model of absence epilepsy, featuring spontaneous spike-wave discharges on electroencephalography (EEG) that are the electrographic hallmark of absence seizures. TRIP8b is an auxiliary subunit of the hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels, which have previously been implicated in the pathogenesis of absence seizures. In contrast to mice lacking the pore-forming HCN channel subunit HCN2, TRIP8b knockout mice exhibited normal cardiac and motor function and a less severe seizure phenotype. Evaluating the circuit that underlies absence seizures, we found that TRIP8b knockout mice had significantly reduced HCN channel expression and function in thalamic-projecting cortical layer 5b neurons and thalamic relay neurons, but preserved function in inhibitory neurons of the reticular thalamic nucleus. Our results expand the known roles of TRIP8b and provide new insight into the region-specific functions of TRIP8b and HCN channels in constraining cortico-thalamo-cortical excitability.
The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017

Depression is a debilitating chronic illness that affects around 350 million people worldwide. Current treatments, such as selective serotonin reuptake inhibitors, are not ideal because only a fraction of patients achieve remission. Tianeptine is an effective antidepressant with a previously unknown mechanism of action. We recently reported that tianeptine is a full agonist at the mu opioid receptor (MOR). Here we demonstrate that the acute and chronic antidepressant-like behavioral effects of tianeptine in mice require MOR. Interestingly, while tianeptine also produces many opiate-like behavioral effects such as analgesia and reward, it does not lead to tolerance or withdrawal. Furthermore, the primary metabolite of tianeptine (MC5), which has a longer half-life, mimics the behavioral effects of tianeptine in a MOR-dependent fashion. These results point to the possibility that MOR and its downstream signaling cascades may be novel targets for antidepressant drug development.
Genetic Architecture of Adaptive Immune System Identifies Key Immune Regulators.
Cell reports, 2018

The immune system is highly diverse, but characterization of its genetic architecture has lagged behind the vast progress made by genome-wide association studies (GWASs) of emergent diseases. Our GWAS for 54 functionally relevant phenotypes of the adaptive immune system in 489 healthy individuals identifies eight genome-wide significant associations explaining 6%-20% of variance. Coding and splicing variants in PTPRC and COMMD10 are involved in memory T cell differentiation. Genetic variation controlling disease-relevant T helper cell subsets includes RICTOR and STON2 associated with Th2 and Th17, respectively, and the interferon-lambda locus controlling regulatory T cell proliferation. Early and memory B cell differentiation stages are associated with variation in LARP1B and SP4. Finally, the latrophilin family member ADGRL2 correlates with baseline pro-inflammatory interleukin-6 levels. Suggestive associations reveal mechanisms of autoimmune disease associations, in particular related to pro-inflammatory cytokine production. Pinpointing these key human immune regulators offers attractive therapeutic perspectives.
Zika virus can directly infect and damage the auditory and vestibular components of the embryonic chicken inner ear.
Developmental dynamics : an official publication of the American Association of Anatomists, 2020

Sensorineural hearing loss is an understudied consequence of congenital Zika syndrome, and balance disorders are essentially unreported to date. Also lacking is information about the susceptibility and the pathogenesis of the developing inner ear following Zika virus (ZIKV) exposure. To address this, ZIKV was delivered directly into the otic cup/otocyst of chicken embryos and infection of inner ear tissues was evaluated using immunohistochemistry.
Optogenetic probing of fast glutamatergic transmission from hypocretin/orexin to histamine neurons in situ.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Hypothalamic hypocretin/orexin (hcrt/orx) neurons coordinate sleep-wake cycles, reward seeking, and body energy balance. Neurochemical data suggest that hcrt/orx cells contain several transmitters, but what hcrt/orx cells release onto their projection targets is unknown. A major pathway by which hcrt/orx neurons are thought to promote arousal is through projections to tuberomammillary histamine (HA) neurons. To study the impact of the electrical activity in hcrt/orx cells on HA neurons, we genetically targeted the light-activated excitatory ion channel channelrhodopsin-2 (ChR2) to the plasma membrane of hcrt/orx cells, and performed patch-clamp recordings from HA cells in acute mouse brain slices. Stimulation of ChR2-containing fibers with millisecond flashes of blue light produced fast postsynaptic currents in HA neurons, with a high connection probability (≈60% of HA cells were connected to ≈40% of hcrt/orx cells expressing ChR2). These inputs depended on tetrodotoxin-sensitive action potentials, had kinetics typical of glutamatergic responses mediated by AMPA receptors, were blocked by the AMPA receptor blocker CNQX, and displayed multiple forms of short-term plasticity (depression in ≈70% trials, facilitation in ≈30% trials, both often in the same cell). Furthermore, stimulation of hcrt/orx axons at physiological frequencies rapidly and reversibly increased action potential firing in HA cells, an effect that was abolished by blockade of AMPA receptors. These results provide the first functional evidence that hcrt/orx neurons are capable of fast glutamatergic control of their projection targets, and suggest that variations in electrical activity of hcrt/orx axons can induce rapid changes in long-range signals generated by HA neurons.
Adaptive integrate-and-fire model reproduces the dynamics of olfactory receptor neuron responses in a moth.
Journal of the Royal Society, Interface, 2019

In order to understand how olfactory stimuli are encoded and processed in the brain, it is important to build a computational model for olfactory receptor neurons (ORNs). Here, we present a simple and reliable mathematical model of a moth ORN generating spikes. The model incorporates a simplified description of the chemical kinetics leading to olfactory receptor activation and action potential generation. We show that an adaptive spike threshold regulated by prior spike history is an effective mechanism for reproducing the typical phasic-tonic time course of ORN responses. Our model reproduces the response dynamics of individual neurons to a fluctuating stimulus that approximates odorant fluctuations in nature. The parameters of the spike threshold are essential for reproducing the response heterogeneity in ORNs. The model provides a valuable tool for efficient simulations of olfactory circuits.
Role of PCDH 1 Gene in the Development of Childhood Asthma and Other Related Phenotypes: A Literature Review.
Cureus, 2018

The asthma gene PCDH 1, encoding protocadherin-1, is a cellular adhesion molecule which plays an important role in epithelial barrier formation and repair. PCDH 1 is a novel susceptible gene not only in childhood asthma but also in eczema and other atopic phenotypes. In this article, we reviewed relevant articles from PubMed, Google Scholar, Science Direct and included all available significant pieces of information about the PCDH 1 association with asthma and other atopic or non-atopic phenotypes. It is very interesting that cigarette smoking can induce changes in PCDH 1 expression but how the changes in PCDH 1 induce asthma is still not clear. PCDH 1 gene polymorphism also sometimes plays role in asthma and bronchial hyperresponsiveness (BHR) pathogenesis as well as in allergic dermatitis.
THERAPEUTIC TARGETING OF BRAIN ARACHIDONIC ACID CASCADE IN BIPOLAR DISORDER BY LOW DOSE ASPIRIN AND CELECOXIB.
Prostaglandins, leukotrienes, and essential fatty acids, 2020

Studies in unanesthetized rats suggest that mood stabilizers approved for treating bipolar disorder downregulate brain arachidonic acid (AA) metabolism. AA plays a role in neurotransmission and neuroinflammation, among other processes. Other drugs that reduce brain AA metabolism may add to mood stabilizer action.
Disproportional effects of Igf2 knockout on placental morphology and diffusional exchange characteristics in the mouse.
The Journal of physiology, 2008

Both complete knockout of the Igf2 gene (Igf2null(+/-)) and knockout of its placental specific transcript alone (Igf2P0(+/-)) lead to fetal growth restriction in mice. However, in the Igf2null(+/-) this growth restriction occurs concurrently in gestation with placental growth restriction, whereas, placental growth restriction precedes fetal growth restriction in the Igf2P0(+/-) mouse. Previous studies have shown that the Igf2P0(+/-) placenta has proportionate reductions in its cellular compartments and its diffusional exchange characteristics. Yet, nothing is known about the structural development or diffusional exchange characteristics of the Igf2null(+/-) mouse. Hence, this study compares the structural properties (using stereology) and diffusional exchange characteristics (using measurement of permeability-surface area product, P.S, of three inert hydrophilic tracers) of the Igf2null(+/-) and the Igf2P0(+/-) placenta to identify the role of Igf2 in the development of the labyrinthine exchange membrane and its functional consequences. Our data show disproportionate effects of complete Igf2 ablation on the compartments of the placenta, not seen when the placental-specific transcript alone is deleted. Furthermore, although the theoretical diffusing capacity (calculated from the stereological data) of the Igf2null(+/-) placenta was reduced relative to control, there was no effect of the complete knockout on permeability surface area available for small hydrophilic tracers. This is in contrast to the Igf2P0(+/-) placenta, where theoretical diffusion capacity and P.S values were reduced similarly. Total ablation of the Igf2 gene from the fetoplacental unit in the mouse therefore results in a disproportionate growth of placental compartments whereas, deleting the placental specific transcript of Igf2 alone results in proportional placental growth restriction. Thus, placental phenotype depends on the degree of Igf2 gene ablation and the interplay between placental and fetal Igf2 in the mouse.
Corticotropin releasing factor dose-dependently modulates excitatory synaptic transmission in the noradrenergic nucleus locus coeruleus.
The European journal of neuroscience, 2017

The noradrenergic nucleus locus coeruleus (LC) is critically involved in the stress response and receives afferent input from a number of corticotropin releasing factor (CRF) containing structures. Several in vivo and in vitro studies in rat have shown that CRF robustly increases the firing rate of LC neurons in a dose-dependent manner. While it is known that these increases are dependent on CRF receptor subtype 1 and mediated by effects of cAMP intracellular signaling cascades on potassium conductance, the impact of CRF on synaptic transmission within LC has not been clarified. In the present study, we used whole-cell patch clamp electrophysiology to assess how varying concentrations of bath-applied CRF affect AMPA-receptor dependent spontaneous excitatory post-synaptic currents (sEPSCs). Compared to vehicle, 10, 25, and 100 nm CRF had no significant effects on any sEPSC parameters. Fifty nanomolar CRF, however, significantly increased sEPSC amplitude, half-width, and charge transfer, while these measures were significantly decreased by 200 nm CRF. These observations suggest that stress may differentially affect ongoing excitatory synaptic transmission in LC depending on how much CRF is released from presynaptic terminals. Combined with the well-documented effects of CRF on membrane properties and spontaneous LC discharge, these observations may help explain how stress and CRF release are able to modulate the signal to noise ratio of LC neurons. These findings have implications for how stress affects the fidelity of signal transmission and information flow through LC and how it might impact norepinephrine release in the CNS.
Spontaneous and electrically modulated spatiotemporal dynamics of the neocortical slow oscillation and associated local fast activity.
NeuroImage, 2013

The neocortical slow oscillation (SO; ~1Hz) of non-REM sleep and anesthesia reflects synchronized network activity composed of alternating active and silent (ON/OFF) phases at the local network and cellular level. The SO itself shows self-organized spatiotemporal dynamics as it appears to originate at unique foci on each cycle and then propagates across the cortical surface. During sleep, this rhythm is relevant for neuroplastic processes mediating memory consolidation especially since its enhancement by slow, rhythmic electrical fields improves subsequent recall. However, the neurobiological mechanism by which spontaneous or enhanced SO activity might operate on memory traces is unknown. Here we show a series of original results, using cycle to cycle tracking across multiple neocortical sites in urethane anesthetized rats: The spontaneous spatiotemporal dynamics of the SO are complex, showing interfering propagation patterns in the anterior-to-posterior plane. These patterns compete for expression and tend to alternate following phase resets that take place during the silent OFF phase of the SO. Applying sinusoidal electrical field stimulation to the anterior pole of the cerebral cortex progressively entrained local field, gamma, and multi-unit activity at all sites, while disrupting the coordination of endogenous SO activity. Field stimulation also biased propagation in the anterior-to-posterior direction and more notably, enhanced the long-range gamma synchrony between cortical regions. These results are the first to show that changes to slow wave dynamics cause enhancements in high frequency cortico-cortical communication and provide mechanistic clues into how the SO is relevant for sleep-dependent memory consolidation.
COMbined Physical and somatoSEnsory training after stroke: Development and description of a novel intervention to improve upper limb function.
Physiotherapy research international : the journal for researchers and clinicians in physical therapy, 2019

After stroke, reach-to-grasp goal-directed movements are disrupted as a result of both residual motor and somatosensory impairments. This report describes the rationale and development of a new upper limb stroke rehabilitation intervention known as COMPoSE: "COMbined Physical and somatoSEnsory training," designed to improve somatosensory and motor deficits in the upper limb after stroke. A standardized training matrix has been developed to facilitate intervention delivery.
Ca²⁺-dependent regulation of Ca²⁺ currents in rat primary afferent neurons: role of CaMKII and the effect of injury.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Currents through voltage-gated Ca²⁺ channels (I(Ca)) may be regulated by cytoplasmic Ca²⁺ levels ([Ca²⁺](c)), producing Ca²⁺-dependent inactivation (CDI) or facilitation (CDF). Since I(Ca) regulates sensory neuron excitability, altered CDI or CDF could contribute to pain generation after peripheral nerve injury. We explored this by manipulating [Ca²⁺](c) while recording I(Ca) in rat sensory neurons. In uninjured neurons, elevating [Ca²⁺](c) with a conditioning prepulse (-15 mV, 2 s) inactivated I(Ca) measured during subsequent test pulses (-15 mV, 5 ms). This inactivation was Ca²⁺-dependent (CDI), since it was decreased with elimination of Ca²⁺ influx by depolarization to above the I(Ca) reversal potential, with high intracellular Ca²⁺ buffering (EGTA 10 mm or BAPTA 20 mm), and with substitution of Ba²⁺ for extracellular Ca²⁺, revealing a residual voltage-dependent inactivation. At longer latencies after conditioning (>6 s), I(Ca) recovered beyond baseline. This facilitation also proved to be Ca²⁺-dependent (CDF) using the protocols limiting cytoplasmic Ca²⁺ elevation. Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) blockers applied by bath (KN-93, myristoyl-AIP) or expressed selectively in the sensory neurons (AIP) reduced CDF, unlike their inactive analogues. Protein kinase C inhibition (chelerythrine) had no effect. Selective blockade of N-type Ca²⁺ channels eliminated CDF, whereas L-type channel blockade had no effect. Following nerve injury, CDI was unaffected, but CDF was eliminated in axotomized neurons. Excitability of sensory neurons in intact ganglia from control animals was diminished after a similar conditioning pulse, but this regulation was eliminated by injury. These findings indicate that I(Ca) in sensory neurons is subject to both CDI and CDF, and that hyperexcitability following injury-induced loss of CDF may result from diminished CaMKII activity.
Listeners' sensitivity to "onset/offset" and "ongoing" interaural delays in high-frequency, sinusoidally amplitude-modulated tones.
The Journal of the Acoustical Society of America, 2008

The relative potency of onset/offset and envelope-based ongoing interaural time delays (ITDs) was assessed using high-frequency stimuli. A two-cue, two-alternative, forced-choice adaptive task was employed to measure threshold ITDs with 100% sinusoidally amplitude-modulated tones centered at 4 kHz. Modulation rates of 125, 250, and 350 Hz were tested with durations of 32, 90, or 240 ms. In the first experiment, ITDs to be detected were imposed only at the onset/offset, only within the ongoing portion, or within both the onset/offset and ongoing portions of the stimuli. Results indicated that ongoing ITDs dominated onset/offset ITDs. The relative potency of ongoing ITDs was directly proportional to duration and inversely proportional to modulation rate. Quantitative analysis suggested that listeners effectively combine onset/offset and ongoing ITDs. Furthermore, the data could be largely accounted for by assuming that listeners attend to the interaural decorrelation of the stimulus resulting from onset/offset and/or ongoing ITDs. A second experiment showed that, (1) overall, an ongoing ITD of one-half period of the envelope had little impact on listeners' sensitivity to delays of the onset/offset and (2) sensitivity to delays within the onset/offset portion of the waveform was reduced by roving the delay within the ongoing portion of the waveform.