rudyvdbrink/CitationDatabase huggingface dataset:
Electrophysiological evidence for voltage-gated calcium channel 2 (Cav2) modulation of mechano- and thermosensitive spinal neuronal responses in a rat model of osteoarthritis.
Neuroscience, 2015

Osteoarthritis (OA) remains one of the greatest healthcare burdens in western society, with chronic debilitating pain-dominating clinical presentation yet therapeutic strategies are inadequate in many patients. Development of better analgesics is contingent on improved understanding of the molecular mechanisms mediating OA pain. Voltage-gated calcium channels 2.2 (Cav2.2) play a critical role in spinal nociceptive transmission, therefore blocking Cav2.2 activity represents an attractive opportunity for OA pain treatment, but the only available licensed Cav2.2 antagonist ziconitide (PrilatTM) is of limited use. TROX-1 is an orally available, use dependent and state-selective Cav2 antagonist, exerting its analgesic effect primarily via Cav2.2 blockade, with an improved therapeutic window compared with ziconitide. Using a rat model of monosodium iodoacetate (MIA), 2 mg, induced OA we used in vivo electrophysiology to assess the effects of spinal or systemic administration of TROX-1 on the evoked activity of wide dynamic range spinal dorsal horn neurons in response to electrical, natural mechanical (dynamic brush and von Frey 2, 8, 26 and 6 g) and thermal (40, 45 and 45 °C) stimuli applied to the peripheral receptive field. MIA injection into the knee joint resulted in mechanical hypersensitivity of the ipsilateral hind paw and weight-bearing asymmetry. Spinal administration of TROX-1 (0.1 and 1 μg/50 μl) produced a significant dose-related inhibition of dynamic brush, mechanical (von Frey filament (vF) 8, 26 and 60 g) and noxious thermal-(45 and 48 °C) evoked neuronal responses in MIA rats only. Systemic administration of TROX-1 produced a significant inhibition of the mechanical-(vF 8, 26 and 60 g) evoked neuronal responses in MIA rats. TROX-1 did not produce any significant effect on any neuronal measure in Sham controls. Our in vivo electrophysiological results demonstrate a pathological state-dependent effect of TROX-1, which suggests an increased functional role of Cav2, likely Cav2.2, channels in mediating OA pain.
Unravel a neuroactive sHA sulfation pattern with neurogenesis activity by a library of defined oligosaccharides.
European journal of medicinal chemistry, 2019

Sulfated hyaluronic acid (sHA) is chemically synthetic mimetic of glycosaminoglycan (GAG) presenting promising biological functions. Specific sulfation pattern, termed as sulfation code plays critical roles in regulating the binding mode between GAG and proteins. As a structural analogue of chondroitin sulfate (CS), sHA bears much higher molecular weight and is nearly free of other proteoglycan contaminants. These properties make sHA a better bioscaffold to build safer and more functionalized material. However, chemical sulfonation process on naked HA polysaccharide produces random sulfation patterns which makes it difficult in disclosing the SAR. Herein, we utilized sHA and CS oligosaccharides with defined sulfation pattern to unravel the SAR between sHA and neurogenesis. We demonstrate sHA tetrasaccharide bearing 6-O-sulfation (sHA-6S) but not other sulfation patterns bind to growth factors at nanomolar range and promote the neurite outgrowth of rat E18 hippocampal neurons in vitro. Furthermore, synthetic sHA polysaccharide enriched in 6-O-sulfation also promote the hippocampal neurite outgrowth in vitro. Our work provides an effective method to disclose the bioactive sulfation pattern of sHA. Our results indicate that a specific sHA sulfation pattern could direct important physiological processes and open the way for the application of sHA-6S in neuroscience and medicine.
Psychoanalysis on the couch: can neuroscience provide the answers?
Medical hypotheses, 2010

Over a century after Freud's attempt to establish psychoanalysis as a natural science, there is renewed interest in the integration of psychoanalytic and neuroscientific findings within a single theoretical and experimental framework. However, it is important that any intellectual exchange is not motivated only by declining confidence in psychoanalytic theory and practice or awareness of the rising fortunes of the brain sciences. The present paper considers three possible ways in which psychoanalysis and neuroscience might be integrated. These include the investigation of the neurological organisation of psychoanalytically defined phenomena; the evaluation of psychoanalytic theories based on their neurobiological evidence; and the use of neuroimaging techniques to assess the progress and outcome of psychoanalytic treatment. The author argues that these exercises are unlikely to provide psychoanalysis with the "unlimited opportunities for overcoming its uncertainties and doubts" that some have anticipated. For instance, the argument that mapping psychoanalytically defined phenomena in the brain may provide biological validity to these phenomena should be considered an expression of logical confusion; the evaluation of psychoanalytic theories based on their biological evidence is critically dependent on speculative interpretation of what the theories predict at neuronal level; and the supposedly objective evaluation of the progress and outcome of psychoanalytic treatment on the basis of neurobiological data relies on the subjective reports of the patient and analyst. In light of this conclusion, there are a number of outstanding questions which remain to be addressed, including whether psychoanalysis should adhere to scientific canons and whether this would necessarily require an experimental methodology.
Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial.
Lancet (London, England), 2014

Choroideremia is an X-linked recessive disease that leads to blindness due to mutations in the CHM gene, which encodes the Rab escort protein 1 (REP1). We assessed the effects of retinal gene therapy with an adeno-associated viral (AAV) vector encoding REP1 (AAV.REP1) in patients with this disease.
Effects of 5HT1A Activation on Gating Profile Following 5HT Depletion in Rats Lacking Social Attachment Since Weanling.
Psychiatry investigation, 2018

Central 5-HT1A receptor is involved in the modulation of sensorimotor gating function. However, its precise role is not clearly defined in developmentally social deprived (isolation rearing, IR) rats featured with impaired sensorimotor gating ability. We therefore aimed to examine the effects of 5HT1A activation on acoustic startle response (ASR) and prepulse inhibition (PPI) in IR rats in a condition of compromised presynaptic 5-HT functions.
A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials.
Scientific reports, 2017

There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects. We then characterized the effects of these compounds on OPC proliferation and differentiation in mouse glial cultures, and on myelination and remyelination in organotypic cultures. Three molecules, edaravone, 5-methyl-7-methoxyisoflavone and lovastatin, gave positive results in all screening tiers. We validated the results by retesting independent stocks of the compounds, analyzing their purity, and performing dose-response curves. To identify the chemical features that may be modified to enhance the compounds' activity, we tested chemical analogs and identified, for edaravone, the functional groups that may be essential for its activity. Among the selected remyelinating candidates, edaravone appears to be of strong interest, also considering that this drug has been approved as a neuroprotective agent for acute ischemic stroke and amyotrophic lateral sclerosis in Japan.
A mismatch between supply and demand of social support in dementia care: a qualitative study on the perspectives of spousal caregivers and their social network members.
International psychogeriatrics, 2018

ABSTRACTBackground:Access to social support contributes to feelings of independence and better social health. This qualitative study aims to investigate multi-informant perspectives on informal social support in dementia care networks.
Easi-CRISPR: a robust method for one-step generation of mice carrying conditional and insertion alleles using long ssDNA donors and CRISPR ribonucleoproteins.
Genome biology, 2017

Conditional knockout mice and transgenic mice expressing recombinases, reporters, and inducible transcriptional activators are key for many genetic studies and comprise over 90% of mouse models created. Conditional knockout mice are generated using labor-intensive methods of homologous recombination in embryonic stem cells and are available for only ~25% of all mouse genes. Transgenic mice generated by random genomic insertion approaches pose problems of unreliable expression, and thus there is a need for targeted-insertion models. Although CRISPR-based strategies were reported to create conditional and targeted-insertion alleles via one-step delivery of targeting components directly to zygotes, these strategies are quite inefficient.
Tropical ataxic neuropathy: Findings of a neuroepidemiological survey of Odeda, southwest Nigeria.
Journal of the neurological sciences, 2019

Tropical ataxic neuropathy seems to have dwindled in public health importance in Nigeria despite the high consumption of cassava-based meals by a huge proportion of people in local Nigerian communities. Yet a recent report suggest its persistence in the same ethnogeographic setting where it was first reported in Nigeria. Our objective was to investigate the prevalence of tropical ataxic neuropathy in Odeda, Ogun state, southwest Nigeria inhabited by a different ethnic group compared to Epe where the disease was first described.
The impact of multiple sclerosis onset symptom on cardiac repolarization.
Brain and behavior, 2017

Multiple sclerosis is associated with prolonged cardiac repolarization but the underlying physiology has remained unknown. In this study, we compared cardiac repolarization during the relapsing-remitting multiple sclerosis (RRMS) disease course in patients with motor and sensory onset symptom.
Neutrophil infiltrates and eosinophil aggregates in chronic rhinosinusitis with nasal polyps and EGPA.
Clinical rheumatology, 2021

The histopathological study of inflammatory cells and their tendency to form aggregates in chronic rhinosinusitis with nasal polyps (CRSwNP) has shown promising results in determining the pathogenesis and predicting clinical outcome. Bilateral nasal polyps also occur in over 70% of patients with eosinophilic granulomatosis with polyangiitis (EGPA). The study aim was to investigate neutrophil infiltrates and eosinophil aggregates in CRSwNP and EGPA tissues of Caucasian patients.
Sequential activation of microglia and astrocyte cytokine expression precedes increased Iba-1 or GFAP immunoreactivity following systemic immune challenge.
Glia, 2016

Activation of the peripheral immune system elicits a coordinated response from the central nervous system. Key to this immune to brain communication is that glia, microglia, and astrocytes, interpret and propagate inflammatory signals in the brain that influence physiological and behavioral responses. One issue in glial biology is that morphological analysis alone is used to report on glial activation state. Therefore, our objective was to compare behavioral responses after in vivo immune (lipopolysaccharide, LPS) challenge to glial specific mRNA and morphological profiles. Here, LPS challenge induced an immediate but transient sickness response with decreased locomotion and social interaction. Corresponding with active sickness behavior (2-12 h), inflammatory cytokine mRNA expression was elevated in enriched microglia and astrocytes. Although proinflammatory cytokine expression in microglia peaked 2-4 h after LPS, astrocyte cytokine, and chemokine induction was delayed and peaked at 12 h. Morphological alterations in microglia (Iba-1(+)) and astrocytes (GFAP(+)), however, were undetected during this 2-12 h timeframe. Increased Iba-1 immunoreactivity and de-ramified microglia were evident 24 and 48 h after LPS but corresponded to the resolution phase of activation. Morphological alterations in astrocytes were undetected after LPS. Additionally, glial cytokine expression did not correlate with morphology after four repeated LPS injections. In fact, repeated LPS challenge was associated with immune and behavioral tolerance and a less inflammatory microglial profile compared with acute LPS challenge. Overall, induction of glial cytokine expression was sequential, aligned with active sickness behavior, and preceded increased Iba-1 or GFAP immunoreactivity after LPS challenge.
Auditory neuropathy--neural and synaptic mechanisms.
Nature reviews. Neurology, 2016

Sensorineural hearing impairment is the most common form of hearing loss, and encompasses pathologies of the cochlea and the auditory nerve. Hearing impairment caused by abnormal neural encoding of sound stimuli despite preservation of sensory transduction and amplification by outer hair cells is known as 'auditory neuropathy'. This term was originally coined for a specific type of hearing impairment affecting speech comprehension beyond changes in audibility: patients with this condition report that they "can hear but cannot understand". This type of hearing impairment can be caused by damage to the sensory inner hair cells (IHCs), IHC ribbon synapses or spiral ganglion neurons. Human genetic and physiological studies, as well as research on animal models, have recently shown that disrupted IHC ribbon synapse function--resulting from genetic alterations that affect presynaptic glutamate loading of synaptic vesicles, Ca(2+) influx, or synaptic vesicle exocytosis--leads to hearing impairment termed 'auditory synaptopathy'. Moreover, animal studies have demonstrated that sound overexposure causes excitotoxic loss of IHC ribbon synapses. This mechanism probably contributes to hearing disorders caused by noise exposure or age-related hearing loss. This Review provides an update on recently elucidated sensory, synaptic and neural mechanisms of hearing impairment, their corresponding clinical findings, and discusses current rehabilitation strategies as well as future therapies.
The genetic aspects of multiple sclerosis.
Annals of Indian Academy of Neurology, 2009

THE EPIDEMIOLOGY OF MULTIPLE SCLEROSIS HAS BEEN EXTENSIVELY INVESTIGATED AND TWO FEATURES HAVE CONSISTENTLY EMERGED: marked geographical variation in prevalence and substantial familial clustering. At first sight, geographic variation would seem to imply an environmental cause for the disease, while familial clustering would seem to suggest that genetic factors have the predominant etiological effect. However, given that geographic variation in prevalence could result from variation in the frequency of genetic risk alleles and that familial clustering might result from shared environmental exposure rather than shared genetic risk alleles, it is clear that these crude inferences are unreliable. Epidemiologists have been resourceful in their attempts to resolve this apparent conflict between "nurture and nature" and have employed a whole variety of sophisticated methods to try and untangle the etiology of multiple sclerosis. The body of evidence that has emerged from these efforts has formed the foundation for decades of research seeking to identify relevant genes and this is the obvious place to start any consideration of the genetics of multiple sclerosis.
PAPupuncture has localized and long-lasting antinociceptive effects in mouse models of acute and chronic pain.
Molecular pain, 2012

Acupuncture has been used for millennia to treat pain, although its efficacy and duration of action is limited. Acupuncture also has brief (1-2 h) antinociceptive effects in mice and these effects are dependent on localized adenosine A₁ receptor (A₁R) activation. Intriguingly, adenosine 5'-monophosphate (AMP) is basally elevated near acupuncture points. This finding suggested that it might be possible to inhibit nociception for a longer period of time by injecting prostatic acid phosphatase (PAP, ACPP) into acupuncture points. PAP is an ectonucleotidase that dephosphorylates extracellular AMP to adenosine, has a long half-life in vivo and is endogenously found in muscle tissue surrounding acupuncture points. Here, we found that injection of PAP into the popliteal fossa--a space behind the knee that encompasses the Weizhong acupuncture point--had dose- and A₁R-dependent antinociceptive effects in mouse models of acute and chronic pain. These inhibitory effects lasted up to six days following a single injection, much longer than the hour-long inhibition provided by acupuncture. Antinociception could be transiently boosted with additional substrate (AMP) or transiently blocked with an A₁R antagonist or an inhibitor of phospholipase C. This novel therapeutic approach--which we term "PAPupuncture"--locally inhibits pain for an extended period of time (100x acupuncture), exploits a molecular mechanism that is common to acupuncture, yet does not require acupuncture needle stimulation.
Interdependence between dorsal and ventral hippocampus during spatial navigation.
Brain and behavior, 2019

The hippocampus is linked to the formation and retrieval of episodic memories and spatial navigation. In rats, it is an elongated structure divided into dorsal (septal) and ventral (temporal) regions paralleling the respective division in the posterior and anterior hippocampus in humans. The dorsal hippocampus has been suggested to be more important for spatial processing and the ventral to processing anxiety-based behaviors. Far less is known regarding the degree to which these different regions interact during information processing. The anatomical connectivity suggests a flow of information between the dorsal and ventral regions; conversely, there are also commissural connections to the contralateral hippocampus. The current study examined the extent to which information from the dorsal hippocampus interacts with processing in the ipsilateral and contralateral ventral hippocampus following the acquisition of a spatial task.
Aberrant plasticity in the hippocampus after neonatal seizures.
The International journal of neuroscience, 2018

Purpose/aim of the study: Neonatal seizures are the most frequent type of neurological disorder, and those newborn babies that experience seizures carry an increased risk of epileptogenesis and other long-term morbidities. The aims of this review were to summarize the different effects on hippocampal neurogenesis between neonatal seizures and adult seizures.
A cis-regulatory signature for chordate anterior neuroectodermal genes.
PLoS genetics, 2010

One of the striking findings of comparative developmental genetics was that expression patterns of core transcription factors are extraordinarily conserved in bilaterians. However, it remains unclear whether cis-regulatory elements of their target genes also exhibit common signatures associated with conserved embryonic fields. To address this question, we focused on genes that are active in the anterior neuroectoderm and non-neural ectoderm of the ascidian Ciona intestinalis. Following the dissection of a prototypic anterior placodal enhancer, we searched all genomic conserved non-coding elements for duplicated motifs around genes showing anterior neuroectodermal expression. Strikingly, we identified an over-represented pentamer motif corresponding to the binding site of the homeodomain protein OTX, which plays a pivotal role in the anterior development of all bilaterian species. Using an in vivo reporter gene assay, we observed that 10 of 23 candidate cis-regulatory elements containing duplicated OTX motifs are active in the anterior neuroectoderm, thus showing that this cis-regulatory signature is predictive of neuroectodermal enhancers. These results show that a common cis-regulatory signature corresponding to K50-Paired homeodomain transcription factors is found in non-coding sequences flanking anterior neuroectodermal genes in chordate embryos. Thus, field-specific selector genes impose architectural constraints in the form of combinations of short tags on their target enhancers. This could account for the strong evolutionary conservation of the regulatory elements controlling field-specific selector genes responsible for body plan formation.
Information transmission for one-dimensional stimuli: the role of strategies.
Acta psychologica, 2009

Important evidence about the information flow between perceptual and motor processes has been obtained from the lateralized readiness potential (LRP) recorded in two-choice go/nogo tasks. Here, we investigated the effect of time pressure on information transmission for one-dimensional stimuli (four squares differing in size). In between- and within-subject designs, respectively, Experiments 1 and 2 showed that under time pressure partial information initiates hand decision and response preparation before complete size information is available. These findings appear to be at odds with the asynchronous discrete coding model. Experiment 3 assessed the mechanisms behind these effects by manipulating the relative difficulty of extracting hand- and go/nogo-specific information from the size of the stimuli. Consistent with asynchronous coding, our results suggest that serial-consecutive processes in extracting partial and full size information may occur also for one-dimensional stimuli. Our data are inconclusive as to the question of discreteness or continuity of information transmission. On a more general level, our data support the notion of flexibility in the coding of perceptual dimensions to adapt performance to environmental conditions.