rudyvdbrink/CitationDatabase huggingface dataset:
mTOR signaling in the nucleus accumbens mediates behavioral sensitization to methamphetamine.
Progress in neuro-psychopharmacology & biological psychiatry, 2018

Chronic psychostimulant treatment in rodents readily produces behavioral sensitization, which reflects altered brain function in response to repeated drug exposure. Numerous morphological and biochemical investigations implicate altered neural plasticity in striatal medium spiny neurons (MSNs) as an essential component in behavioral sensitization. The mammalian target of the rapamycin (mTOR) signaling pathway, a key regulator of synaptic neuroplasticity, in the ventral striatum of methamphetamine (METH) -sensitized mice was investigated to determine if a link exists with the development of METH sensitization. Behaviorally, METH-sensitized mice possessed increased levels of phosphorylated mTOR/S2448 and its down-stream regulator p70S6K and pS6 in the ventral striatum. Systemic treatment with rapamycin, a specific mTOR inhibitor, coincident with a daily METH injection suppressed the induction of METH sensitization and reduced the number of dendritic spines in the shell and core of the nucleus accumbens. The infusion of lentivirus-expressing mTOR-shRNA into the shell region of the nucleus accumbens inhibited the induction of behavioral sensitization to METH, which was comparable to the effect of rapamycin. These results suggest that mTORC1-mediated signaling in the nucleus accumbens mediates the development of behavioral sensitization to METH.
Food deprivation and nicotine correct akinesia and freezing in Na(+) -leak current channel (NALCN)-deficient strains of Caenorhabditis elegans.
Genes, brain, and behavior, 2014

Mutations in various genes adversely affect locomotion in model organisms, and thus provide valuable clues about the complex processes that control movement. In Caenorhabditis elegans, loss-of-function mutations in the Na(+) leak current channel (NALCN) and associated proteins (UNC-79 and UNC-80) cause akinesia and fainting (abrupt freezing of movement during escape from touch). It is not known how defects in the NALCN induce these phenotypes or if they are chronic and irreversible. Here, we report that akinesia and freezing are state-dependent and reversible in NALCN-deficient mutants (nca-1;nca-2, unc-79 and unc-80) when additional cation channels substitute for this protein. Two main measures of locomotion were evaluated: spontaneous movement (traversal of >2 head lengths during a 5 second observation period) and the touch-freeze response (movement greater than three body bends in response to tail touch). Food deprivation for as little as 3 min stimulated spontaneous movement and corrected the touch-freeze response. Conversely, food-deprived animals that moved normally in the absence of bacteria rapidly reverted to uncoordinated movement when re-exposed to food. The effects of food deprivation were mimicked by nicotine, which suggested that acetylcholine mediated the response. Nicotine appeared to act on interneurons or motor neurons rather than directly at the neuromuscular junction because levamisole, which stimulates muscle contraction, did not correct movement. Neural circuits have been proposed to account for the effects of food deprivation and nicotine on spontaneous movement and freezing. The NALCN may play an unrecognized role in human movement disorders characterized by akinesia and freezing gait.
Cannabinoid modulation of executive functions.
European journal of pharmacology, 2008

Executive functions are higher-order cognitive processes such as attention, behavioural flexibility, decision-making, inhibitory control, planning, time estimation and working memory that exert top-down control over behaviour. In addition to the role of cannabinoid signaling in other cognitive functions such as mnemonic processes, interest in its involvement in executive functions has arisen more recently. Here, we will briefly review some of the recent findings indicating a modulatory role of cannabinoid action on executive functioning. In addition, a growing body of evidence suggests that in particular adolescents are more vulnerable for the deleterious effects of drugs of abuse such as cannabis on cognitive functioning. Therefore, in this paper we will also briefly discuss some recent developments in this research field.
Impulsive Aggression as a Comorbidity of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents.
Journal of child and adolescent psychopharmacology, 2016

This article examines the characteristics of impulsive aggression (IA) as a comorbidity in children and adolescents with attention-deficit/hyperactivity disorder (ADHD), focusing on its incidence, impact on ADHD outcomes, need for timely intervention, and limitations of current treatment practices.
Dietary supplementation with acetyl-l-carnitine in seizure treatment of pentylenetetrazole kindled mice.
Neurochemistry international, 2012

In spite of the availability of new antiepileptic drugs a considerable number of epilepsy patients still have pharmacoresistant seizures, and thus there is a need for novel approaches. Acetyl-l-carnitine (ALCAR), which delivers acetyl units to mitochondria for acetyl-CoA production, has been shown to improve brain energy homeostasis and protects against various neurotoxic insults. To our knowledge, this is the first study of ALCAR's effect on metabolism in pentylenetetrazole (PTZ) kindled mice. ALCAR or the commonly used antiepileptic drug valproate, was added to the drinking water of mice for 25days, and animals were injected with PTZ or saline three times a week during the last 21 days. In order to investigate ALCAR's effects on glucose metabolism, mice were injected with [1-(13)C]glucose 15 min prior to microwave fixation. Brain extracts from cortex and the hippocampal formation (HF) were studied using (1)H and (13)C NMR spectroscopy and HPLC. PTZ kindling caused glucose hypometabolism, evidenced by a reduction in both glycolysis and TCA cycle turnover in both brain regions investigated. Glutamatergic and GABAergic neurons were affected in cortex and HF, but the amount of glutamate was only reduced in HF. Slight astrocytic involvement could be detected in the cortex. Interestingly, the dopamine content was increased in the HF. ALCAR attenuated the PTZ induced reduction in [3-(13)C]alanine and the increase in dopamine in the HF. However, TCA cycle metabolism was not different from that seen in PTZ kindled animals. In conclusion, even though ALCAR did not delay the kindling process, it did show some promising ameliorative effects, worthy of further investigation.
Action Observation of Motor Skills Followed by Immediate Sleep Enhances the Motor Rehabilitation of Older Adults With Stroke.
Journal of geriatric physical therapy (2001), 2017

Motor rehabilitation following stroke is a demanding challenge in search for new strategies to improve outcome. Rehabilitation through action observation has been reported beneficial for older adults recovering from stroke. Early sleep session following motor learning enhanced the performance of the acquired motor skills. The purpose of this study was to examine whether an early sleep session following action observation has benefit over action observation alone in the rehabilitation of older adults after stroke.
Mechanical thrombectomy as the primary treatment for acute basilar artery occlusion: experience from 5 years of practice.
Journal of neurointerventional surgery, 2013

Most studies of the treatment for acute basilar occlusion focus on intravenous or intra-arterial thrombolysis whereas data on mechanical thrombectomy as the preferred treatment for acute basilar occlusion are scarce. In this study, data are presented on 28 patients treated with mechanical thrombectomy as the preferred treatment for basilar artery occlusion.
Living Life With My Child's Pain: The Parent Pain Acceptance Questionnaire (PPAQ).
The Clinical journal of pain, 2015

Parents' emotional, cognitive, and behavioral responses are highly influential on children's pain and functional outcomes. One important response to pediatric pain is acceptance: the degree to which an individual participates in routine daily activities in the presence of pain and is willing to let pain be a part of their life without efforts to control or avoid it. However, no tool currently exists to assess parents' own acceptance of their child's pain. The aim of this study was to validate the Parent Pain Acceptance Questionnaire (PPAQ).
Gut microbiota composition is associated with temperament traits in infants.
Brain, behavior, and immunity, 2019

One of the key behavioral phenotypes in infancy are different temperament traits, and certain early life temperament traits have been shown to precede later mental health problems. Differences in the gut microbiota composition (GMC) have been suggested to link with neurodevelopment. For example, toddler temperament traits have been found to associate with differences in GMC; however, studies in infants are lacking although infancy is a rapid period of neurodevelopment as well as GM development. Thus, we aimed to investigate association between infant GMC and temperament.
The role of type 2 diabetes in neurodegeneration.
Neurobiology of disease, 2015

A growing body of evidence links type-2 diabetes (T2D) with dementia and neurodegenerative diseases such as Alzheimer's disease (AD). AD is the most common form of dementia and is characterised neuropathologically by the accumulation of extracellular beta amyloid (Aβ) peptide aggregates and intracellular hyper-phosphorylated tau protein, which are thought to drive and/or accelerate inflammatory and oxidative stress processes leading to neurodegeneration. Although the precise mechanism remains unclear, T2D can exacerbate these neurodegenerative processes. Brain atrophy, reduced cerebral glucose metabolism and CNS insulin resistance are features of both AD and T2D. Cell culture and animal studies have indicated that the early accumulation of Aβ may play a role in CNS insulin resistance and impaired insulin signalling. From the viewpoint of insulin resistance and impaired insulin signalling in the brain, these are also believed to initiate other aspects of brain injury, including inflammatory and oxidative stress processes. Here we review the clinical and experimental pieces of evidence that link these two chronic diseases of ageing, and discuss underlying mechanisms. The evaluation of treatments for the management of diabetes in preclinical, and clinical studies and trials for AD will also be discussed.
Cannabinoid receptor 2 activation: a means to prevent monocyte-endothelium engagement.
The American journal of pathology, 2013

This Commentary highlights the article by Rom et al which shows that selective cannabinoid receptor 2 activation in leukocytes decreases key steps in monocyte-blood brain barrier engagement suppressing inflammatory leukocyte responses and preventing neuroinflammation.
Ultrasound-tagged near-infrared spectroscopy does not disclose absent cerebral circulation in brain-dead adults.
British journal of anaesthesia, 2018

Near-infrared spectroscopy, a non-invasive technique for monitoring cerebral oxygenation, is widely used, but its accuracy is questioned because of the possibility of extra-cranial contamination. Ultrasound-tagged near-infrared spectroscopy (UT-NIRS) has been proposed as an improvement over previous methods. We investigated UT-NIRS in healthy volunteers and in brain-dead patients.
A novel inducible tyrosine kinase receptor to regulate signal transduction and neurite outgrowth.
Journal of neuroscience research, 2009

Nervous system growth factor gene delivery can promote axonal growth and prevent cell death in animal models of CNS trauma and neurodegenerative diseases. The ability to regulate growth factor expression or signaling pathways downstream from growth factor receptors remains a desirable goal for in vivo gene transfer. To achieve precise pharmacological modulation of neurotrophin activity, we have generated a chimeric trkA receptor (ItrkA) by fusing the entire intracellular domain of the trkA high-affinity NGF receptor to two intracellular, modified FK506 binding domains for the synthetic small molecule dimerization ligand AP20187. Rat PC12 cells were transduced with lentiviral vectors containing ItrkA and green fluorescent protein (GFP; via an internal ribosome entry site). Treatment of ItrkA-expressing PC12 cells with AP20187 induced neurite outgrowth and differentiation in a time- and dose-dependent fashion, with a half-maximal response at a concentration of 1 nM AP20187. Seventy percent of cells responded to AP20187 by day 3. Western blots demonstrated that AP20187 treatment resulted in phosphorylation of Erk1/2 and Akt in ItrkA-transduced PC12 cells but not in nontransduced, naïve cells. Phosphorylation levels were comparable to levels obtained with 50 ng/ml nerve growth factor (NGF). In addition, ItrkA lentiviral transduction of primary E15 dorsal root ganglion neurons significantly increased neurite growth three- to fourfold in the presence of AP20187 compared with control GFP transduced and naïve neurons. These results demonstrate that small ligand-induced dimerization of the intracellular domain of trkA can efficiently simulate the biological activity of NGF and provide a means to regulate intracellular neurotrophin receptor signaling.
Modelling the distribution of white matter hyperintensities due to ageing on MRI images using Bayesian inference.
NeuroImage, 2019

White matter hyperintensities (WMH), also known as white matter lesions, are localised white matter areas that appear hyperintense on MRI scans. WMH commonly occur in the ageing population, and are often associated with several factors such as cognitive disorders, cardiovascular risk factors, cerebrovascular and neurodegenerative diseases. Despite the fact that some links between lesion location and parametric factors such as age have already been established, the relationship between voxel-wise spatial distribution of lesions and these factors is not yet well understood. Hence, it would be of clinical importance to model the distribution of lesions at the population-level and quantitatively analyse the effect of various factors on the lesion distribution model. In this work we compare various methods, including our proposed method, to generate voxel-wise distributions of WMH within a population with respect to various factors. Our proposed Bayesian spline method models the spatio-temporal distribution of WMH with respect to a parametric factor of interest, in this case age, within a population. Our probabilistic model takes as input the lesion segmentation binary maps of subjects belonging to various age groups and provides a population-level parametric lesion probability map as output. We used a spline representation to ensure a degree of smoothness in space and the dimension associated with the parameter, and formulated our model using a Bayesian framework. We tested our algorithm output on simulated data and compared our results with those obtained using various existing methods with different levels of algorithmic and computational complexity. We then compared the better performing methods on a real dataset, consisting of 1000 subjects of the UK Biobank, divided in two groups based on hypertension diagnosis. Finally, we applied our method on a clinical dataset of patients with vascular disease. On simulated dataset, the results from our algorithm showed a mean square error (MSE) value of 7.27×10
Perspectives on recent advances in the understanding and treatment of Parkinson's disease.
European journal of neurology, 2009

There have been numerous important recent advances in our understanding of the causes of Parkinson's disease (PD), the treatments available and how these are best applied for the long-term management of patients. Novel genes causing familial PD have been discovered and mechanisms leading to cell dysfunction and death identified. The PD prodrome is now a subject of great interest and clinical markers are being defined that may in future, together with biochemical markers, support an early, pre-motor diagnosis of PD. This will become important as new therapies are developed to modify disease progression. In the interim, the optimization of existing therapies remains an important priority. The value of existing and novel continuous drug delivery systems in PD is seen as providing simplified regimens, maintenance of motor control, reduction in motor complications and improved patient adherence to drug use.
Repurposing beta-3 adrenergic receptor agonists for Alzheimer's disease: beneficial effects in a mouse model.
Alzheimer's research & therapy, 2021

Old age, the most important risk factor for Alzheimer's disease (AD), is associated with thermoregulatory deficits. Brown adipose tissue (BAT) is the main thermogenic driver in mammals and its stimulation, through β3 adrenergic receptor (β3AR) agonists or cold acclimation, counteracts metabolic deficits in rodents and humans. Studies in animal models show that AD neuropathology leads to thermoregulatory deficits, and cold-induced tau hyperphosphorylation is prevented by BAT stimulation through cold acclimation. Since metabolic disorders and AD share strong pathogenic links, we hypothesized that BAT stimulation through a β3AR agonist could exert benefits in AD as well.
Forward Processing of Object-Location Association from the Ventral Stream to Medial Temporal Lobe in Nonhuman Primates.
Cerebral cortex (New York, N.Y. : 1991), 2020

While the hippocampus (HPC) is a prime candidate combining object identity and location due to its strong connections to the ventral and dorsal pathways via surrounding medial temporal lobe (MTL) areas, recent physiological studies have reported spatial information in the ventral pathway and its downstream target in MTL. However, it remains unknown whether the object-location association proceeds along the ventral MTL pathway before HPC. To address this question, we recorded neuronal activity from MTL and area anterior inferotemporal cortex (TE) of two macaques gazing at an object to retain its identity and location in each trial. The results showed significant effects of object-location association at a single-unit level in TE, perirhinal cortex (PRC), and HPC, but not in the parahippocampal cortex. Notably, a clear area difference emerged in the association form: 1) representations of object identity were added to those of subjects' viewing location in TE; 2) PRC signaled both the additive form and the conjunction of the two inputs; and 3) HPC signaled only the conjunction signal. These results suggest that the object and location signals are combined stepwise at TE and PRC each time primates view an object, and PRC may provide HPC with the conjunctional signal, which might be used for encoding episodic memory.
Effects of chronic cannabinoid exposure during adolescence on reward preference and mPFC activation in adulthood.
Physiology & behavior, 2019

Cannabis is one of the most commonly used drugs among adolescents, with initial use beginning between the ages of 12 to 17. Although often perceived as a 'soft drug', both short- and long-term use have been associated with numerous adverse outcomes, including cognitive impairment, increased risk of substance abuse, and heightened risk of psychosis or schizophrenia in individuals with a predisposition. Further, the severity of these impairments is closely linked to initiation of use, i.e. earlier use increases risk. It has been suggested that adolescent vulnerability to the adverse consequences of cannabis use is due to ongoing brain development occurring during this time. Indeed, the adolescent brain continues to be remodeled well into adolescence and early adulthood, particularly in the prefrontal cortex (PFC). The medial prefrontal cortex (mPFC) has been implicated in reward processing and decision-making and alterations in mPFC development due to adolescent cannabis exposure could impair these functions. To model the effects of cannabis on mPFC function, we administered the synthetic cannabinoid WIN 55, 212-2 (WIN) to male and female rats from postnatal day 30-60. Once animals reached adulthood, we used a Probabilistic Reward (PR) choice task to elicit PFC activity and measure how patterns of activity to task-related events were modulated by adolescent WIN-treatment. Adult animals showed subtle effects of WIN-treatment on choice patterns. During task performance, mPFC activity elicited by lever press at the time of choices and reward delivery following choices were reduced in WIN-treated animals. This lasting effect of WIN suggests an impairment of the maturation of excitatory-inhibitory balance of signals in mPFC during adolescence, which may alter executive function into adulthood.
Antipsychotic drug exposure and risk of fracture: a systematic review and meta-analysis of observational studies.
International clinical psychopharmacology, 2018

To investigate the extent to which exposure to first-generation and second-generation antipsychotics (APs) is associated with an increased risk of fractures, with a particular focus on hip fractures, and to ascertain the risk associated with exposure to individual drugs. We included observational studies that reported data on fractures in individuals exposed to APs compared with unexposed individuals or individuals with previous exposure. We extracted information on study design, source of data, population characteristics, outcomes of interest, matching and confounding factors, and used a modified version of the Newcastle-Ottawa Scale to judge study risk of bias. We pooled adjusted estimates of relative effects to generate pooled odds ratios (ORs) and their 95% confidence interval (CI) using a random-effects model. We rated the quality of evidence using the GRADE approach. Of 36 observational studies, 29 proved to have a low risk of bias and seven were found to have a high risk of bias. The risk of hip fracture (OR: 1.57, 95% CI: 1.42-1.74, low quality of evidence) and of any fracture (OR: 1.17, 95% CI: 1.04-1.31, very low quality of evidence) increased with exposure to APs, with similar increases in risk in the first generation and second generation. The risk was similar among different diagnostic categories. The few studies that provided data were insufficient to allow inferences on individual drugs. AP exposure in unselected populations was associated with a 57% increase in the risk of hip fractures and a 17% increase in the risk of any fractures. Between-study heterogeneity limits the confidence in this estimate.