rudyvdbrink/CitationDatabase huggingface dataset:
Lesion of the centromedian thalamic nucleus in MPTP-treated monkeys.
Movement disorders : official journal of the Movement Disorder Society, 2008

The caudal intralaminar nuclei are a major source of glutamatergic afferents to the basal ganglia. Experiments in the 6-hydroxydopamine rat model have shown that the parafascicular nucleus is overactive and its lesion alleviates basal ganglia neurochemical abnormalities associated with dopamine depletion. Accordingly, removal of this excitatory innervation of the basal ganglia could have a beneficial value in the parkinsonian state. To test this hypothesis, unilateral kainate-induced chemical ablation of the centromedian thalamic nucleus (CM) has been performed in MPTP-treated monkeys. Successful lesions restricted to the CM boundaries (n = 2) without spreading over other neighboring thalamic nuclei showed an initial, short-lasting, and mild change in the parkinsonian motor scale but no effect against levodopa-induced dyskinesias. The lack of significant and persistent motor improvement leads us to conclude that unilateral selective lesion of the CM alone cannot be considered as a suitable surgical approach for the treatment of PD or levodopa-induced dyskinesias. The role of the caudal intralaminar nuclei in the pathophysiology of movement disorders of basal ganglia origin remains to be clarified.
Efficacy of intensive short-term dynamic psychotherapy in mood disorders: A critical review.
Journal of affective disorders, 2020

Intensive Short-Term Dynamic Psychotherapy (ISTDP) is an intervention introduced by Davanloo in order to treat anxiety, mood and somatic symptom, and personality disorders. It is a brief intervention aiming to identify and process painful or forbidden emotions and consequently to override symptoms and self-destructive tendencies. In this review we examine the efficacy of ISTDP on symptoms in patients with Major Depressive Disorder (MDD) and Bipolar Disorder (BD).
Differential regulation of GnRH secretion in the preoptic area (POA) and the median eminence (ME) in male mice.
Endocrinology, 2015

GnRH release in the median eminence (ME) is the central output for control of reproduction. GnRH processes in the preoptic area (POA) also release GnRH. We examined region-specific regulation of GnRH secretion using fast-scan cyclic voltammetry to detect GnRH release in brain slices from adult male mice. Blocking endoplasmic reticulum calcium reuptake to elevate intracellular calcium evokes GnRH release in both the ME and POA. This release is action potential dependent in the ME but not the POA. Locally applied kisspeptin induced GnRH secretion in both the ME and POA. Local blockade of inositol triphospate-mediated calcium release inhibited kisspeptin-induced GnRH release in the ME, but broad blockade was required in the POA. In contrast, kisspeptin-evoked secretion in the POA was blocked by local gonadotropin-inhibitory hormone, but broad gonadotropin-inhibitory hormone application was required in the ME. Although action potentials are required for GnRH release induced by pharmacologically-increased intracellular calcium in the ME and kisspeptin-evoked release requires inositol triphosphate-mediated calcium release, blocking action potentials did not inhibit kisspeptin-induced GnRH release in the ME. Kisspeptin-induced GnRH release was suppressed after blocking both action potentials and plasma membrane Ca(2+) channels. This suggests that kisspeptin action in the ME requires both increased intracellular calcium and influx from the outside of the cell but not action potentials. Local interactions among kisspeptin and GnRH processes in the ME could thus stimulate GnRH release without involving perisomatic regions of GnRH neurons. Coupling between action potential generation and hormone release in GnRH neurons is thus likely physiologically labile and may vary with region.
Activation of extracellular regulated kinase and mechanistic target of rapamycin pathway in focal cortical dysplasia.
Neuropathology : official journal of the Japanese Society of Neuropathology, 2016

Neuropathology of resected brain tissue has revealed an association of focal cortical dysplasia (FCD) with drug-resistant epilepsy (DRE). Recent studies have shown that the mechanistic target of rapamycin (mTOR) pathway is hyperactivated in FCD as evidenced by increased phosphorylation of the ribosomal protein S6 (S6) at serine 240/244 (S(240/244) ), a downstream target of mTOR. Moreover, extracellular regulated kinase (ERK) has been shown to phosphorylate S6 at serine 235/236 (S(235/236) ) and tuberous sclerosis complex 2 (TSC2) at serine 664 (S(664) ) leading to hyperactive mTOR signaling. We evaluated ERK phosphorylation of S6 and TSC2 in two types of FCD (FCD I and FCD II) as a candidate mechanism contributing to mTOR pathway dysregulation. Tissue samples from patients with tuberous sclerosis (TS) served as a positive control. Immunostaining for phospho-S6 (pS6(240/244) and pS6(235/236) ), phospho-ERK (pERK), and phospho-TSC2 (pTSC2) was performed on resected brain tissue with FCD and TS. We found increased pS6(240/244) and pS6(235/236) staining in FCD I, FCD II and TS compared to normal-appearing tissue, while pERK and pTSC2 staining was increased only in FCD IIb and TS tissue. Our results suggest that both the ERK and mTOR pathways are dysregulated in FCD and TS; however, the signaling alterations are different for FCD I as compared to FCD II and TS.
N,O-Benzamide difluoroboron complexes as near-infrared probes for the detection of β-amyloid and tau fibrils.
Chemical communications (Cambridge, England), 2020

In this study, a series of organo difluoroboron probes with a BF2 benzamide moiety was designed, prepared and evaluated. Among them, 2c displayed the best optical and biological properties, and may be used as a useful near-infrared fluorescent probe for the detection of Aβ plaques and neurofibrillary tangles in AD.
Consequences of converting graded to action potentials upon neural information coding and energy efficiency.
PLoS computational biology, 2014

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na(+) and K(+) channels, with generator potential and graded potential models lacking voltage-gated Na(+) channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na(+) channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a 'footprint' in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation.
Hearing in slow-motion: Humans underestimate the speed of moving sounds.
Scientific reports, 2015

Perception can often be described as a statistically optimal inference process whereby noisy and incomplete sensory evidence is combined with prior knowledge about natural scene statistics. Previous evidence has shown that humans tend to underestimate the speed of unreliable moving visual stimuli. This finding has been interpreted in terms of a Bayesian prior favoring low speed, given that in natural visual scenes objects are mostly stationary or slowly-moving. Here we investigated whether an analogous tendency to underestimate speed also occurs in audition: even if the statistics of the visual environment seem to favor low speed, the statistics of the stimuli reaching the individual senses may differ across modalities, hence potentially leading to different priors. Here we observed a systematic bias for underestimating the speed of unreliable moving sounds. This finding suggests the existence of a slow-motion prior in audition, analogous to the one previously found in vision. The nervous system might encode the overall statistics of the world, rather than the specific properties of the signals reaching the individual senses.
Effects of melatonin on the nitric oxide system and protein nitration in the hypobaric hypoxic rat hippocampus.
BMC neuroscience, 2015

It is well documented that the nitric oxide (NO) might be directly involved in brain response to hypobaric hypoxia, and could contribute to memory deficiencies. Recent studies have shown that melatonin could attenuate hypoxia or ischemia-induced nerve injuries by decreasing the production of free radicals. The present study, using immunohistochemical and immunoblot methods, aimed to explore whether melatonin treatment may affect the expression of nitric oxide system and protein nitration, and provide neuroprotection in the rat hippocampus injured by hypobaric hypoxia. Prior to hypoxic treatment, adult rats were pretreated with melatonin (100 mg/kg, i.p.) before they were exposed to the altitude chamber with 48 Torr of the partial oxygen concentration (pO2) for 7 h to mimic the ambience of being at 9000 m in height. They were then sacrificed after 0 h, 1, and 3 days of reoxygenation.
Jaw-neck movement integration in 6-year-old children differs from that of adults.
Journal of oral rehabilitation, 2020

A functional integration between the jaw and neck regions during purposive jaw movements is well described in adults, but there is a lack of knowledge of such integration during jaw function in children.
Tryptophan depletion impairs object-recognition memory in the rat: reversal by risperidone.
Behavioural brain research, 2010

Tryptophan depletion techniques are effective in reducing central serotonergic function and have been used to investigate its role in mood and cognition. In the present study a tryptophan-free diet was fed to Lister-hooded male rats chronically for 21 days to investigate the effect of lowering central serotonin concentration on cognition using the novel object-recognition paradigm. Chronically tryptophan-depleted rats had impaired object-recognition memory; this was accompanied by a reduction in central serotonin of 40-50% in the hippocampus, frontal cortex and striatum. In a subsequent experiment, the atypical antipsychotic, risperidone (0.2 mg/kg), but not the typical antipsychotic, haloperidol (0.1 mg/kg), administered i.p. 30 min prior to the retention test, significantly attenuated the chronic tryptophan depletion impairment. These data show that chronic lowering of central serotonin is associated with impaired cognitive performance, and that this can be reversed by the atypical antipsychotic, risperidone.
Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation.
PLoS computational biology, 2017

The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh) and norepinephrine (NE) and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations) that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed.
Behavioral traits predicting alcohol drinking in outbred rats: an investigation of anxiety, novelty seeking, and cognitive flexibility.
Alcoholism, clinical and experimental research, 2012

Most adults in Western society consume alcohol regularly without negative consequences. For a small subpopulation, however, drinking can quickly progress to excessive and chronic intake. Given the dangers associated with alcohol abuse, it is critical to identify traits that may place an individual at risk for developing these behaviors. To that end, we used a rat model to determine whether anxiety-related behaviors, novelty seeking, or cognitive flexibility predict excessive alcohol drinking under both limited and continuous access conditions.
Membrane-tethered monomeric neurexin LNS-domain triggers synapse formation.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Neurexins are presynaptic cell-adhesion molecules that bind to postsynaptic cell-adhesion molecules such as neuroligins and leucine-rich repeat transmembrane proteins (LRRTMs). When neuroligins or LRRTMs are expressed in a nonneuronal cell, cocultured neurons avidly form heterologous synapses onto that cell. Here we show that knockdown of all neurexins in cultured hippocampal mouse neurons did not impair synapse formation between neurons, but blocked heterologous synapse formation induced by neuroligin-1 or LRRTM2. Rescue experiments demonstrated that all neurexins tested restored heterologous synapse formation in neurexin-deficient neurons. Neurexin-deficient neurons exhibited a decrease in the levels of the PDZ-domain protein CASK (a calcium/calmodulin-activated serine/threonine kinase), which binds to neurexins, and mutation of the PDZ-domain binding sequence of neurexin-3β blocked its transport to the neuronal surface and impaired heterologous synapse formation. However, replacement of the C-terminal neurexin sequence with an unrelated PDZ-domain binding sequence that does not bind to CASK fully restored surface transport and heterologous synapse formation in neurexin-deficient neurons, suggesting that no particular PDZ-domain protein is essential for neurexin surface transport or heterologous synapse formation. Further mutagenesis revealed, moreover, that the entire neurexin cytoplasmic tail was dispensable for heterologous synapse formation in neurexin-deficient neurons, as long as the neurexin protein was transported to the neuronal cell surface. Furthermore, the single LNS-domain (for laminin/neurexin/sex hormone-binding globulin-domain) of neurexin-1β or neurexin-3β, when tethered to the presynaptic plasma membrane by a glycosylinositolphosphate anchor, was sufficient for rescuing heterologous synapse formation in neurexin-deficient neurons. Our data suggest that neurexins mediate heterologous synapse formation via an extracellular interaction with presynaptic and postsynaptic ligands without the need for signal transduction by the neurexin cytoplasmic tail.
miR-155 Is Essential for Inflammation-Induced Hippocampal Neurogenic Dysfunction.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

Peripheral and CNS inflammation leads to aberrations in developmental and postnatal neurogenesis, yet little is known about the mechanism linking inflammation to neurogenic abnormalities. Specific miRs regulate peripheral and CNS inflammatory responses. miR-155 is the most significantly upregulated miR in primary murine microglia stimulated with lipopolysaccharide (LPS), a proinflammatory Toll-Like Receptor 4 ligand. Here, we demonstrate that miR-155 is essential for robust IL6 gene induction in microglia under LPS stimulation in vitro. LPS-stimulated microglia enhance astrogliogenesis of cocultured neural stem cells (NSCs), whereas blockade of IL6 or genetic ablation of microglial miR-155 restores neural differentiation. miR-155 knock-out mice show reversal of LPS-induced neurogenic deficits and microglial activation in vivo. Moreover, mice with transgenic elevated expression of miR-155 in nestin-positive neural and hematopoietic stem cells, including microglia, show increased cell proliferation and ectopically localized doublecortin-positive immature neurons and radial glia-like cells in the hippocampal dentate gyrus (DG) granular cell layer. Microglia have proliferative and neurogenic effects on NSCs, which are significantly altered by microglial miR-155 overexpression. In addition, miR-155 elevation leads to increased microglial numbers and amoeboid morphology in the DG. Our study demonstrates that miR-155 is essential for inflammation-induced neurogenic deficits via microglial activation and induction of IL6 and is sufficient for disrupting normal hippocampal development.
Genetic influences on dietary variety - results from a twin study.
Appetite, 2014

The heritability of variety seeking in the food domain was estimated from a large sample (N = 5,543) of middle age to elderly monozygotic and dizygotic twins from the "Virginia 30,000" twin study. Different dietary variety scores were calculated based on a semi-quantitative food choice questionnaire that assessed consumption frequencies and quantities for a list of 99 common foods. Results indicate that up to 30% of the observed variance in dietary variety was explained through heritable influences. Most of the differences between twins were due to environmental influences that are not shared between twins. Additional non-genetic analyses further revealed a weak relationship between dietary variety and particular demographic variables, including socioeconomic status, age, sex, religious faith, and the number of people living in the same household.
Phenotypes of reinforcement sensitivity as predictors of the response to acute antidepressant treatment in rats.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2021

One of the biggest threats to modern societies is the increasing prevalence of mood disorders. Cognitive deficits associated with depressive and bipolar disorders are a major driver of functional impairment and the ensuing disability of the suffering individuals. Growing evidence has indicated strong inter-individual differences in the vulnerability to development and effectivity of treatment of these psychiatric conditions, linking various levels of reinforcement sensitivity with specific mood conditions. In this study, we took a unique opportunity to investigate how trait sensitivity to reinforcement determines the reactivity of rats to acute antidepressant treatment. For this, using a preclinical version of the probabilistic reversal-learning (PRL) paradigm, we identified 4 phenotypes of sensitivity to negative and positive feedback in rats, which could represent various types of potential vulnerability to affective disorders. Subsequently, using the light/dark box (LDB) and progressive ratio schedule of reinforcement (PRSR) tests, we evaluated inter-phenotypic differences in the effects of acute treatment with 3 different antidepressant drugs (escitalopram, mirtazapine and clomipramine, each in 3 doses) on anxiety and appetitive motivation of experimental animals. We report statistically significant differences between the investigated phenotypes of reinforcement sensitivity in the effects of acute escitalopram treatment on anxiety in the LDB test. We also report phenotype-independent effects of mirtazapine on motivation and anxiety and a lack of effect of clomipramine. These results demonstrate for the first time that trait sensitivity to reinforcement could have important implications for the effectiveness of treatment in affective disorders.
Orthostatic hypotension and symptomatic subclinical orthostatic hypotension increase risk of cognitive impairment: an integrated evidence review and analysis of a large older adult hypertensive cohort.
European heart journal, 2018

Systematically reviewing the literature found orthostatic hypotension (OH) to be associated with an increased risk of incident dementia but limited data were available in those at highest risk, the hypertensive oldest-old. Our aim was to analyse the relationship between OH and incident cognitive decline or dementia in this group and to synthesize the evidence base overall.
Piezo2 expression in corneal afferent neurons.
The Journal of comparative neurology, 2014

Recently, a novel class of mechanically sensitive channels has been identified and have been called Piezo channels. In this study, we explored Piezo channel expression in sensory neurons supplying the guinea pig corneal epithelium, which have well-defined modalities in this species. We hypothesized that a proportion of corneal afferent neurons express Piezo2, and that these neurons are neurochemically distinct from corneal polymodal nociceptors or cold-sensing neurons. We used a combination of retrograde tracing to identify corneal afferent neurons and double label in situ hybridization and/or immunohistochemistry to determine their molecular and/or neurochemical profile. We found that Piezo2 expression occurs in ∼26% of trigeminal ganglion neurons and 30% of corneal afferent neurons. Piezo2 corneal afferent neurons are almost exclusively non-calcitonin gene-related peptide (CGRP)-immunoreactive (-IR), medium- to large-sized neurons that are NF200-IR, suggesting they are not corneal polymodal nociceptors. There was no coexpression of Piezo2 and transient receptor potential cation channel subfamily M member 8 (TRPM8) transcripts in any corneal afferent neurons, further suggesting that Piezo2 is not expressed in corneal cold-sensing neurons. We also noted that TRPM8-IR or CGRP-IR corneal afferent neurons are almost entirely small and lack NF200-IR. Piezo2 expression occurs in a neurochemically distinct subpopulation of corneal afferent neurons that are not polymodal nociceptors or cold-sensing neurons, and is likely confined to a subpopulation of pure mechano-nociceptors in the cornea. This provides the first evidence in an in vivo system that Piezo2 is a strong candidate for a channel that transduces noxious mechanical stimuli.
Land use mix and five-year mortality in later life: Results from the Cognitive Function and Ageing Study.
Health & place, 2016

This study explores the potential modifying effect of age and mediation effect of co-morbidity on the association between land use mix, a measure of neighbourhood walkability, and five-year mortality among the 2424 individuals participating in the year-10 follow-up of the Cognitive Function and Ageing Study in England. Postcodes of participants were mapped onto Lower-layer Super Output Areas, a small area level geographical unit in the UK, and linked to Generalised Land Use data. Cox regression models were fitted to investigate the association. For the younger older age group (75-79 years), the effect of high land use mix on an elevated risk of mortality was mediated by co-morbidity. For older old age groups (80-84, 85+ years), a higher land use mix was directly associated with a 10% lower risk of five-year mortality. The findings suggest differential impacts of land use mix on the health of the younger and older old.