rudyvdbrink/CitationDatabase huggingface dataset:
A critical review of the mechanism of action for the selective serotonin reuptake inhibitors: do these drugs possess anti-inflammatory properties and how relevant is this in the treatment of depression?
Neuropharmacology, 2013

The selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed pharmacological treatment for depression. Since their introduction many have considered the primary mechanism by which the SSRIs produced therapeutic improvement in depression is their effect on monoaminergic signalling. In recent years, however, the credibility of the monoamine theory and the therapeutic efficacy of these compounds in the treatment of depression has been extensively criticized. In the current review the legitimacy of these criticisms is critically examined, in many instances the evidence base used to support these criticisms is found to be weak. Nevertheless, the apparent 'failure' of the monoamine theory has been of benefit in motivating research into alternative mechanisms through which the SSRIs may act. Given research demonstrating that depressive symptoms are intimately linked with disturbances in pro-inflammatory signalling, perhaps the most promising discovery has been the realisation that SSRIs posses significant anti-inflammatory properties. These recent findings are discussed and contextualised with respect to the neurogenic, neurotrophic and gluatamatergic effects that these drugs also possess.
Microglia density decreases in the rat rostral nucleus of the solitary tract across development and increases in an age-dependent manner following denervation.
Neuroscience, 2017

Microglia are critical for developmental pruning and immune response to injury, and are implicated in facilitating neural plasticity. The rodent gustatory system is highly plastic, particularly during development, and outcomes following nerve injury are more severe in developing animals. The mechanisms underlying developmental plasticity in the taste system are largely unknown, making microglia an attractive candidate. To better elucidate microglia's role in the taste system, we examined these cells in the rostral nucleus of the solitary tract (rNTS) during normal development and following transection of the chorda tympani taste nerve (CTX). Rats aged 5, 10, 25, or 50days received unilateral CTX or no surgery and were sacrificed four days later. Brain tissue was stained for Iba1 or CD68, and both the density and morphology of microglia were assessed on the intact and transected sides of the rNTS. We found that the intact rNTS of neonatal rats (9-14days) shows a high density of microglia, most of which appear reactive. By 29days of age, microglia density significantly decreased to levels not significantly different from adults and microglia morphology had matured, with most cells appearing ramified. CD68-negative microglia density increased following CTX and was most pronounced for juvenile and adult rats. Our results show that microglia density is highest during times of normal gustatory afferent pruning. Furthermore, the quantity of the microglia response is higher in the mature system than in neonates. These findings link increased microglia presence with instances of normal developmental and injury induced alterations in the rNTS.
Cognitive rigidity and BDNF-mediated frontostriatal glutamate neuroadaptations during spontaneous nicotine withdrawal.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2020

Cognitive flexibility is the ability to switch strategic responses adaptively in changing environments. Cognitive rigidity imposed by neural circuit adaptations during nicotine abstinence may foster maladaptive nicotine taking in addicts. We systematically examined the effects of spontaneous withdrawal in mice exposed to either nicotine (6.3 or 18 mg/kg/day) or saline for 14 days on cognitive flexibility using an operant strategy set-shifting task. Because frontostriatal circuits are critical for cognitive flexibility and brain-derived neurotrophic factor (BDNF) modulates glutamate plasticity in these circuits, we also explored the effects of nicotine withdrawal on these neurochemical substrates. Mice undergoing nicotine withdrawal required more trials to attain strategy-switching criterion. Error analysis show that animals withdrawn from both nicotine doses committed higher perseverative errors, which correlated with measures of anxiety. However, animals treated with the higher nicotine dose also displayed more strategy maintenance errors that remained independent of negative affect. BDNF mRNA expression increased in the medial prefrontal cortex (mPFC) following nicotine withdrawal. Surprisingly, BDNF protein declined in mPFC but was elevated in dorsal striatum (DS). DS BDNF protein positively correlated with perseverative and maintenance errors, suggesting mPFC-DS overflow of BDNF during withdrawal. BDNF-evoked glutamate release and synapsin phosphorylation was attenuated within DS synapses, but enhanced in the nucleus accumbens, suggesting a dichotomous role of BDNF signaling in striatal regions. Taken together, these data suggest that spontaneous nicotine withdrawal impairs distinct components of cognitive set-shifting and these deficits may be linked to BDNF-mediated alterations in glutamate signaling dynamics in discrete frontostriatal circuits.
Composite impulsivity-related domains in college students.
Journal of psychiatric research, 2017

Impulsivity is a complex, multidimensional construct with prior theoretically and empirically derived characterizations of impulsivity-related behaviors varying considerably among studies. We assessed college students (N = 440) longitudinally with five impulsivity-related self-reported assessments and two computerized behavioral measures. Using a combination of exploratory and confirmatory factor analysis (CFA), we derived then validated several composite impulsivity-related domains (CIRDs). These factors replicated, in large part, findings from a previous study conducted by our group in an independent sample that used a similar analytical approach. The four CIRDs derived in current study are: 'Impulsive action', 'Approach/Appetite Motivation', 'Impulsivity/Compulsivity' and 'Experience and thrill seeking/Fearlessness'. Subsequent psychometric analyses found these CIRDs were relatively stable over the two-year period. Moreover, multiple regression analysis found that CIRD profiles associated with clinical and behavioral characteristics including anxiety, depression, attention deficit hyperactivity disorder and substance use symptomology. Overall, our data suggest that empirically-derived CIRDs have potential for organizing previous impulsivity-related constructs into a more naturalistic framework where distinct constructs are often expressed together in the same individuals. This framework might facilitate future research of neuropsychiatric disorder risk and etiology.
Genetic dissection reveals that Akt is the critical kinase downstream of LRRK2 to phosphorylate and inhibit FOXO1, and promotes neuron survival.
Human molecular genetics, 2014

Leucine-rich repeat kinase 2 (LRRK2) is a complex kinase and mutations in LRRK2 are perhaps the most common genetic cause of Parkinson's disease (PD). However, the identification of the normal physiological function of LRRK2 remains elusive. Here, we show that LRRK2 protects neurons against apoptosis induced by the Drosophila genes grim, hid and reaper. Genetic dissection reveals that Akt is the critical downstream kinase of LRRK2 that phosphorylates and inhibits FOXO1, and thereby promotes survival. Like human LRRK2, Drosophila lrrk also promotes neuron survival; lrrk loss-of-function mutant displays reduced cell numbers, which can be rescued by LRRK2 expression. Importantly, LRRK2 G2019S and LRRK2 R1441C mutants impair the ability of LRRK2 to activate Akt, and fail to prevent apoptotic death. Ectopic expression of a constitutive active form of Akt hence is sufficient to rescue this functional deficit. These data establish that LRRK2 can protect neurons from apoptotic insult through a survival pathway in which LRRK2 signals to activate Akt, and then inhibits FOXO1. These results might indicate that a LRRK-Akt therapeutic pathway to promote neuron survival and to prevent neurodegeneration in Parkinson's disease.
Enhancing group cognitive-behavioral therapy for hoarding disorder with between-session Internet-based clinician support: A feasibility study.
Journal of clinical psychology, 2018

Hoarding disorder (HD) is difficult to treat. In an effort to increase efficacy and engagement in cognitive-behavioral therapy (CBT), we developed and evaluated a novel intervention comprising group CBT combined with between-session Internet-based clinician support for people with HD.
A neural network for online spike classification that improves decoding accuracy.
Journal of neurophysiology, 2020

Separating neural signals from noise can improve brain-computer interface performance and stability. However, most algorithms for separating neural action potentials from noise are not suitable for use in real time and have shown mixed effects on decoding performance. With the goal of removing noise that impedes online decoding, we sought to automate the intuition of human spike-sorters to operate in real time with an easily tunable parameter governing the stringency with which spike waveforms are classified. We trained an artificial neural network with one hidden layer on neural waveforms that were hand-labeled as either spikes or noise. The network output was a likelihood metric for each waveform it classified, and we tuned the network's stringency by varying the minimum likelihood value for a waveform to be considered a spike. Using the network's labels to exclude noise waveforms, we decoded remembered target location during a memory-guided saccade task from electrode arrays implanted in prefrontal cortex of rhesus macaque monkeys. The network classified waveforms in real time, and its classifications were qualitatively similar to those of a human spike-sorter. Compared with decoding with threshold crossings, in most sessions we improved decoding performance by removing waveforms with low spike likelihood values. Furthermore, decoding with our network's classifications became more beneficial as time since array implantation increased. Our classifier serves as a feasible preprocessing step, with little risk of harm, that could be applied to both off-line neural data analyses and online decoding.
Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease.
Nature reviews. Neuroscience, 2010

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action.
Promethazine protects against 3-nitropropionic acid-induced neurotoxicity.
Neurochemistry international, 2010

Promethazine (PMZ), an FDA-approved antihistaminergic drug, was identified as a potentially neuroprotective compound in a NINDS screening program. It was shown to protect against ischemia in mice, to delay disease onset in a mouse model of amyotrophic lateral sclerosis and to inhibit Ca(2+)-induced mitochondrial permeability transition in rat liver mitochondria. We investigated whether PMZ could protect against the neurotoxic effects induced by 3-nitropropionic acid (3-NP), an inhibitor of the succinate dehydrogenase, used to model Huntington's disease (HD) in rats. Lewis rats receiving chronic subcutaneous infusion of 3-NP were treated with PMZ. The findings indicate that chronic PMZ treatment significantly reduced 3-NP-induced striatal lesion volume, loss of GABAergic neurons and number of apoptotic cells in the striatum. PMZ showed a strong neuroprotective effect against 3-NP toxicity in vivo.
CSF-1 controls cerebellar microglia and is required for motor function and social interaction.
The Journal of experimental medicine, 2019

Microglia, the brain resident macrophages, critically shape forebrain neuronal circuits. However, their precise function in the cerebellum is unknown. Here we show that human and mouse cerebellar microglia express a unique molecular program distinct from forebrain microglia. Cerebellar microglial identity was driven by the CSF-1R ligand CSF-1, independently of the alternate CSF-1R ligand, IL-34. Accordingly, CSF-1 depletion from Nestin
Polymorphic color vision in captive Uta Hick's cuxiús, or bearded sakis (Chiropotes utahickae).
American journal of primatology, 2015

The pitheciines (Chiropotes, Pithecia, and Cacajao) are frugivorous Neotropical primates that specialize on the predation of seeds from unripe fruits, usually cryptic against the foliage. However, little is known about the color vision distribution within this taxon, and even less about the abilities shared by these animals regarding discrimination of chromatic targets. The aim of this study was to evaluate the color vision perception of captive Uta Hick's cuxiús, or bearded sakis (Chiropotes utahickae) through a behavioral paradigm of color visual discrimination, as well as to estimate, by genetic studies, the number and kinds of medium to long wavelength cone photopigment (opsins) encoded by this species. Among 12 cuxiús (7 males and 5 females) studied only 1 female was diagnosed as a trichromat. Results from genotyping were in line with our behavioral data and showed that cuxiús carried one (dichromat) or two (trichromat) medium to long wavelength pigments alleles, demonstrating a color vision polymorphism in C. utahickae similar to the majority of Neotropical Primates.
Blockade of nicotine reward and reinstatement by activation of alpha-type peroxisome proliferator-activated receptors.
Biological psychiatry, 2011

Recent findings indicate that inhibitors of fatty acid amide hydrolase (FAAH) counteract the rewarding effects of nicotine in rats. Inhibition of FAAH increases levels of several endogenous substances in the brain, including the endocannabinoid anandamide and the noncannabinoid fatty acid ethanolamides oleoylethanolamide (OEA) and palmitoylethanolamide, which are ligands for alpha-type peroxisome proliferator-activated nuclear receptors (PPAR-α). Here, we evaluated whether directly acting PPAR-α agonists can modulate reward-related effects of nicotine.
Thrombolysis and thrombectomy in patients treated with dabigatran with acute ischemic stroke: Expert opinion.
International journal of stroke : official journal of the International Stroke Society, 2017

Systemic thrombolysis with rt-PA is contraindicated in patients with acute ischemic stroke anticoagulated with dabigatran. This expert opinion provides guidance on the use of the specific reversal agent idarucizumab followed by rt-PA and/or thrombectomy in patients with ischemic stroke pre-treated with dabigatran. The use of idarucizumab followed by rt-PA is covered by the label of both drugs.
Quantitative neuroimaging in mucolipidosis type IV.
Molecular genetics and metabolism, 2014

Mucolipidosis type IV (MLIV) is an autosomal recessive disorder resulting from mutations in the MCOLN1 gene. This gene encodes the endosomal/lysosomal transient receptor potential channel protein mucolipin-1 (TRPML1). Affected patients suffer from neurodevelopmental abnormalities and progressive retinal dystrophy. In a prospective natural history study we hypothesized the presence of an additional slow cerebral neurodegenerative process. We have recruited 5 patients, tested their neurodevelopmental status, and measured cerebral regional volumes and white matter integrity using MRI yearly. Over a period of up to 3 years, MLIV patients remained neurologically stable. There was a trend for increased cortical and subcortical gray matter volumes and increased ventricular size, while white matter and cerebellar volumes decreased. Mean diffusivity (MD) was increased and fractional anisotropy (FA) values were below normal in all analyzed brain regions. There was a positive correlation between motor scores of the Vineland Scale and the FA values in the corticospinal tract (corr coef 0.39), and a negative correlation with the MD values (corr coef -0.50) in the same brain region. We conclude from these initial findings that deficiency in mucolipin-1 affects the entire brain but that there might be a selective regional cerebral neurodegenerative process in MLIV. In addition, these data suggest that diffusion-weighted imaging might be a good biomarker for following patients with MLIV. Therefore, our findings may be helpful for designing future clinical trials.
Adolescent decision-making in Canadian medical contexts: Integrating neuroscience and consent frameworks.
Paediatrics & child health, 2018

The primary objective of this commentary is to integrate current neuroscientific research on brain development during adolescence, with existing consent frameworks that do not designate a minimum age for eligibility to consent to, or refuse medical treatment. To reach this objective, the three consent frameworks used in health care settings are outlined: age-based framework; mature minor framework and capacity-based framework. This commentary draws on the Canadian health care system specifically to consider consent frameworks that grant young people with decision-making capacity. Next, a brief review of adolescent brain development findings is presented, particularly pertaining to the decision-making capacity of young people within medical contexts. Ultimately, the question of whether the stage of a young person's brain development impedes their capacity to consent to, or refuse medical treatment is addressed. This commentary provides reassurance as to the compatibility between capacity-based and mature minor frameworks to consent to treatment with current neuroscientific understanding of adolescent brain development.
Organization and trade-off of spectro-temporal tuning properties of duration-tuned neurons in the mammalian inferior colliculus.
Journal of neurophysiology, 2014

Neurons throughout the mammalian central auditory pathway respond selectively to stimulus frequency and amplitude, and some are also selective for stimulus duration. First found in the auditory midbrain or inferior colliculus (IC), these duration-tuned neurons (DTNs) provide a potential neural mechanism for encoding temporal features of sound. In this study, we investigated how having an additional neural response filter, one selective to the duration of an auditory stimulus, influences frequency tuning and neural organization by recording single-unit responses and measuring the dorsal-ventral position and spectral-temporal tuning properties of auditory DTNs from the IC of the awake big brown bat (Eptesicus fuscus). Like other IC neurons, DTNs were tonotopically organized and had either V-shaped, U-shaped, or O-shaped frequency tuning curves (excitatory frequency response areas). We hypothesized there would be an interaction between frequency and duration tuning in DTNs, as electrical engineering theory for resonant filters dictates a trade-off in spectral-temporal resolution: sharp tuning in the frequency domain results in poorer resolution in the time domain and vice versa. While the IC is a more complex signal analyzer than an electrical filter, a similar operational trade-off could exist in the responses of DTNs. Our data revealed two patterns of spectro-temporal sensitivity and spatial organization within the IC: DTNs with sharp frequency tuning and broad duration tuning were located in the dorsal IC, whereas cells with wide spectral tuning and narrow temporal tuning were found in the ventral IC.
Addition of dexmedetomidine to QX-314 enhances the onset and duration of sciatic nerve block in rats.
Canadian journal of physiology and pharmacology, 2018

An experimental set-up was designed to observe whether adding dexmedetomidine to QX-314 would enhance the onset and duration of sensory and motor function in a rat sciatic nerve block model. Fifty-six Sprague-Dawley rats received unilateral sciatic nerve blocks with 0.2 mL of 35 mmol/L QX-314 alone, dexmedetomidine (5.3 μmol/L (1 μg/kg), 26.4 μmol/L (5 μg/kg), 52.8 μmol/L (10 μg/kg)) alone, or a combination of the two. Thermal nociception and motor function were assessed by an investigator blinded to the drug treatment, and sciatic nerves and perineural tissues were harvested at 14 days after injection. In addition, we examined the effects of these solutions on compound action potentials in isolated frog sciatic nerves. Dexmedetomidine added to QX-314 enhanced the onset and duration of thermal nociception block and motor block (P < 0.05) without aggravating histopathological injuries. Furthermore, 52.8 μmol/L dexmedetomidine added to 35 mmol/L QX-314 showed less inflammation than QX-314 alone at 14 days (P = 0.003). Dexmedetomidine plus QX-314 was shown to dose-dependently reduce the compound action potentials relative to QX-314 alone (P < 0.05). It was concluded that co-administration of QX-314 with a clinical dose of dexmedetomidine produced a synergistic anesthetic effect to enhance the effect of sciatic nerve block.
Clinical, Pathological, and Molecular Characterization of Infant Medulloblastomas Treated with Sequential High-Dose Chemotherapy.
Pediatric blood & cancer, 2016

High-dose chemotherapy (HDC) strategies were developed to avoid unacceptable neurotoxicity associated with craniospinal irradiation in infants with embryonal brain tumors. However, the impact of molecular and pathological characterizations in such approaches and long-term outcome have not been widely described in young children.
GABA
Brain research bulletin, 2019

Orofacial inflammation could activate satellite glial cells (SGCs) in the trigeminal ganglion (TG) to produce interleukin 1β (IL-1β) which plays crucial roles in the development of inflammatory pain. Recent studies have shown that gamma-amino butyric acid-B (GABA
Active direct current (DC) shifts and "Red slow": two new concepts for seizure mechanisms and identification of the epileptogenic zone.
Neuroscience research, 2020

An accurate identification of the epileptogenic zone is essential for patients with intractable epilepsy who are candidates to neurosurgery. EEG recordings can provide predictive biomarkers of the epileptogenic zone. Wide-band EEG makes it possible to record from infraslow (including DC shifts) to high frequency (HFO, over 300 Hz) oscillations for diagnostic purposes in patients with epilepsy. Although the presence of HFOs have been proposed to sign the epileptogenic zone, DC-like recordings demonstrate that DC shifts precede HFOs at seizure onset. This led to the proposal that "ictal active DC shifts" are causally related to seizure onset as opposed to "ictal passive DC shifts". Thus, active DC shifts may constitute predictive biomarkers of the epileptogenic zone in epilepsy. Since DC shift is commonly associated to a rise in extracellular potassium, potassium homeostasis regulated by Kir4.1 channels in astrocytes may play an key role at seizure onset. In addition, we hypothesize that, during the interictal period, the co-occurrence of slow events and interictal HFOs, so-called "Red slow", may also delineate an epileptogenic zone, even if a seizure would not be actually recorded.