A5045832568- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Memory and Neural Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Ion channel regulation and function
- Functional Brain Connectivity Studies
- EEG and Brain-Computer Interfaces
- Sleep and Wakefulness Research
- Neuroscience and Neural Engineering
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Alzheimer's disease research and treatments
- Phosphodiesterase function and regulation
- Epilepsy research and treatment
- Neurotransmitter Receptor Influence on Behavior
- Treatment of Major Depression
- Cardiac electrophysiology and arrhythmias
- Genetics and Neurodevelopmental Disorders
- Olfactory and Sensory Function Studies
- Photoreceptor and optogenetics research
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal Development and Disorders
- GABA and Rice Research
Lundbeck (Denmark)
2015-2024
Lundbeck Foundation
2016
University of Copenhagen
2015-2016
University of Cambridge
2016
Centro de Investigación Biomédica en Red de Salud Mental
2016
Mental Health Services
2016
NeuroProof (Germany)
2015
University of South Australia
2000
The excitatory amino acid transporters (EAATs) are expressed throughout the central nervous system, where they responsible for reuptake of neurotransmitter (S)-glutamate (Glu).(1) Recently, we have reported discovery first subtype selective EAAT1 inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) (1b) and presented an introductory structure−activity relationship (SAR) study.(2) Here, present a detailed SAR by design,...
<h3>Background:</h3> The hemizygous 22q11.2 microdeletion is a common copy number variant in humans. deletion confers high risk for neurodevelopmental disorders, including autism and schizophrenia. Up to 41% of carriers experience psychotic symptoms. <h3>Methods:</h3> We present new mouse model (Df(h22q11)/+) the syndrome (22q11.2DS) report on, our knowledge, most comprehensive study undertaken date 22q11.2DS models. was conducted male mice. <h3>Results:</h3> found elevated postpubertal...
In the present study, we have elucidated functional characteristics and mechanism of action methaqualone (2-methyl-3-o-tolyl-4(3<i>H</i>)-quinazolinone, Quaalude), an infamous sedative-hypnotic recreational drug from 1960s–1970s. Methaqualone was demonstrated to be a positive allosteric modulator at human <i>α</i><sub>1,2,3,5</sub><i>β</i><sub>2,3</sub><i>γ</i><sub>2S</sub> GABA<sub>A</sub> receptors (GABA<sub>A</sub>Rs) expressed in <i>Xenopus</i> oocytes, whereas it displayed highly...
A microdeletion at locus 15q13.3 is associated with high incidence rates of psychopathology, including schizophrenia. mouse model the syndrome has been generated (Df[h15q13]/+) translational utility for modelling schizophrenia-like pathology. Among other deficits, schizophrenia characterised by dysfunctions in prefrontal cortical (PFC) inhibitory circuitry and attention. The objective this study to assess PFC-dependent functioning Df(h15q13)/+ using electrophysiological, pharmacological,...
The 5-HT6 receptor has emerged as a promising target for cognitive disorders and combining antagonist with an acetylcholinesterase inhibitor (AChEI) represents novel approach the symptomatic treatment of Alzheimer's disease (AD). A recent phase 2 trial showed that selective idalopirdine (Lu AE58054) improved cognition in patients moderate AD on stable AChEI donepezil. Here we investigated effects combination donepezil hippocampal function using vivo electrophysiology microdialysis. Network...
Abstract Quantitative electroencephalography from freely moving rats is commonly used as a translational tool for predicting drug‐effects in humans. We hypothesized that may be expressed differently depending on whether the rat active locomotion or sitting still during recording sessions, and proposed automatic state‐detection viable estimating free of hypo‐/hyperlocomotion‐induced effects. aimed at developing fully validated method detecting two behavioural states: inactive, one‐second...
Preclinical studies indicate that high-frequency oscillations, above 100 Hz (HFO:100-170 Hz), are a potential translatable biomarker for pharmacological studies, with the rapid acting antidepressant ketamine increasing both gamma (40-100 Hz) and HFO.To assess effect of uncompetitive NMDA antagonist ketamine, D-cycloserine (DCS), which acts at glycine site on receptors HFO in humans.We carried out partially double-blind, 4-way crossover study 24 healthy male volunteers. Each participant...
Abstract Na v 1.1 ( SCN 1A ) channels primarily located in gamma‐aminobutyric acid GABA )ergic fast‐spiking interneurons are pivotal for action potential generation and propagation these neurons. Inappropriate function of interneurons, leading to disinhibition pyramidal cells network desynchronization, correlates with decreased cognitive capability. Further, reduced functionality is linked various diseases the central nervous system. There is, at present, however no subtype selective...
To date, the understanding and development of novel treatments for mental illness is hampered by inadequate animal models. For instance, it unclear to what extent commonly used behavioural tests in animals can inform us on affective aspects schizophrenia.To link pathophysiological processes an model clinical findings, we have here utilized recently developed Df(h15q13)/+ mouse detailed investigations cortical neuronal engagement during pre-attentive processing auditory information from two...
Amphetamine (AMP), methylphenidate (MPH), and atomoxetine (ATX) are approved treatments for ADHD, together with nicotine (NIC), represent pharmacological agents widely studied on cognitive domains including attention impulsive action in humans. These thus opportunities clinical observation to be reinvestigated the preclinical setting, i.e., reverse translation. The present study investigated each drug male, Long Evans rats trained perform either (1) five-choice serial reaction time task...
The 5-HT6 receptor is a promising target for cognitive disorders, in particular Alzheimer's disease (AD). high affinity and selective antagonist idalopirdine (Lu AE58054) currently development mild-moderate AD as adjunct therapy to acetylcholinesterase inhibitors (AChEIs). We studied the effects of alone combination with AChEI donepezil on cortical function using two vivo electrophysiological methods. Neuronal network oscillations frontal cortex were measured during electrical stimulation...