rudyvdbrink/CitationDatabase huggingface dataset:
The kynurenine pathway as a therapeutic target in cognitive and neurodegenerative disorders.
British journal of pharmacology, 2013

Understanding the neurochemical basis for cognitive function is one of the major goals of neuroscience, with a potential impact on the diagnosis, prevention and treatment of a range of psychiatric and neurological disorders. In this review, the focus will be on a biochemical pathway that remains under-recognized in its implications for brain function, even though it can be responsible for moderating the activity of two neurotransmitters fundamentally involved in cognition - glutamate and acetylcholine. Since this pathway - the kynurenine pathway of tryptophan metabolism - is induced by immunological activation and stress, it also stands in a unique position to mediate the effects of environmental factors on cognition and behaviour. Targeting the pathway for new drug development could, therefore, be of value not only for the treatment of existing psychiatric conditions, but also for preventing the development of cognitive disorders in response to environmental pressures.
Interleukin-6-mediated functional upregulation of TRPV1 receptors in dorsal root ganglion neurons through the activation of JAK/PI3K signaling pathway: roles in the development of bone cancer pain in a rat model.
Pain, 2015

Primary and metastatic cancers that affect bone are frequently associated with severe and intractable pain. The mechanisms underlying the pathogenesis of bone cancer pain still remain largely unknown. Previously, we have reported that sensitization of primary sensory dorsal root ganglion (DRG) neurons contributes to the pathogenesis of bone cancer pain in rats. In addition, numerous preclinical and clinical studies have revealed the pathological roles of interleukin-6 (IL-6) in inflammatory and neuropathic hyperalgesia. In this study, we investigated the role and the underlying mechanisms of IL-6 in the development of bone cancer pain using in vitro and in vivo approaches. We first demonstrated that elevated IL-6 in DRG neurons plays a vital role in the development of nociceptor sensitization and bone cancer-induced pain in a rat model through IL-6/soluble IL-6 receptor (sIL-6R) trans-signaling. Moreover, we revealed that functional upregulation of transient receptor potential vanilloid channel type 1 (TRPV1) in DRG neurons through the activation of Janus kinase (JAK)/phosphatidylinositol 3-kinase (PI3K) signaling pathway contributes to the effects of IL-6 on the pathogenesis of bone cancer pain. Therefore, suppression of functional upregulation of TRPV1 in DRG neurons by the inhibition of JAK/PI3K pathway, either before surgery or after surgery, reduces the hyperexcitability of DRG neurons and pain hyperalgesia in bone cancer rats. We here disclose a novel intracellular pathway, the IL-6/JAK/PI3K/TRPV1 signaling cascade, which may underlie the development of peripheral sensitization and bone cancer-induced pain.
Excitatory extrinsic afferents to striatal interneurons and interactions with striatal microcircuitry.
The European journal of neuroscience, 2019

The striatum constitutes the main input structure of the basal ganglia and receives two major excitatory glutamatergic inputs, from the cortex and the thalamus. Excitatory cortico- and thalamostriatal connections innervate the principal neurons of the striatum, the spiny projection neurons (SPNs), which constitute the main cellular input as well as the only output of the striatum. In addition, corticostriatal and thalamostriatal inputs also innervate striatal interneurons. Some of these inputs have been very well studied, for example the thalamic innervation of cholinergic interneurons and the cortical innervation of striatal fast-spiking interneurons, but inputs to most other GABAergic interneurons remain largely unstudied, due in part to the relatively recent identification and characterization of many of these interneurons. In this review, we will discuss and reconcile some older as well as more recent data on the extrinsic excitatory inputs to striatal interneurons. We propose that the traditional feed-forward inhibitory model of the cortical input to the fast-spiking interneuron then inhibiting the SPN, often assumed to be the prototype of the main functional organization of striatal interneurons, is incomplete. We provide evidence that the extrinsic innervation of striatal interneurons is not uniform but shows great cell-type specificity. In addition, we will review data showing that striatal interneurons are themselves interconnected in a highly cell-type-specific manner. These data suggest that the impact of the extrinsic inputs on striatal activity critically depends on synaptic interactions within interneuronal circuitry.
Cytosolic phospholipase A2 alpha inhibition prevents neuronal NMDA receptor-stimulated arachidonic acid mobilization and prostaglandin production but not subsequent cell death.
Journal of neurochemistry, 2008

Phospholipase A(2) (PLA(2)) enzymes encompass a superfamily of at least 13 extracellular and intracellular esterases that hydrolyze the sn-2 fatty acyl bonds of phospholipids to yield fatty acids and lysophospholipids. The purpose of this study was to characterize which phospholipase paralog regulates NMDA receptor-mediated arachidonic acid (AA) release. Using mixed cortical cell cultures containing both neurons and astrocytes, we found that [(3)H]-AA released into the extracellular medium following NMDA receptor stimulation (100 microM) increased with time and was completely prevented by the addition of the NMDA receptor antagonist MK-801 (10 microM) or by removal of extracellular Ca(2+). Neither diacylglycerol lipase inhibition (RHC-80267; 10 microM) nor selective inhibition of Ca(2+)-independent PLA(2) [bromoenol lactone (BEL); 10 microM] alone had an effect on NMDA receptor-stimulated release of [(3)H]-AA. Release was prevented by methyl arachidonyl fluorophosphonate (MAFP) (5 microM) and AACOCF(3) (1 microM), inhibitors of both cytosolic PLA(2) (cPLA(2)) and Ca(2+)-independent PLA(2) isozymes. This inhibition effectively translated to block of NMDA-induced prostaglandin (PG) production. An inhibitor of p38MAPK, SB 203580 (7.5 microM), also significantly reduced NMDA-induced PG production providing suggestive evidence for the role of cPLA(2)alpha. Its involvement in release was confirmed using cultures derived from mice deficient in cPLA(2)alpha, which failed to produce PGs in response to NMDA receptor stimulation. Interestingly, neither MAFP, AACOCF(3) nor cultures derived from cPLA(2)alpha null mutant animals showed any protection against NMDA-mediated neurotoxicity, indicating that inhibition of this enzyme may not be a viable protective strategy in disorders of the cortex involving over-activation of the NMDA receptor.
Mutational screening of GABRG2 gene in Pakistani population of Punjab with generalized tonic clonic seizures and children with childhood absence epilepsy.
Journal of the Chinese Medical Association : JCMA, 2018

Epilepsy is a multifaceted and multistep disorder that disrupts the proper functioning of neurons. It is becoming increasingly clear that the responsiveness of neurons depends on the appropriate trafficking of ions across the channels in the membrane of neurons. In line with this notion, impairment among these ion channels due to mutations has gain increasing attention in molecular neuroscience.
Shifting the paradigm: new approaches for characterizing and classifying neurons.
Current opinion in neurobiology, 2009

Efforts to characterize and classify the cellular components of the nervous system have a rich history in modern neuroscience, and closely mirror the development of new techniques to assay cellular properties. Recent advances in high-throughput histology, genetics and neuroinformatics hold great promise for systematic and reproducible measurement and community databasing of cellular properties. In particular, transgenic approaches to reproducibly target and manipulate specific cell types in mice are rapidly advancing. Cre recombinase-based approaches in particular allow the coupling of cell type specificity with a wide variety of genetic tools for visualization, molecular profiling, tract tracing and functional manipulation. The reproducible multimodal characterization allowed by these transgenics provides a means to classify, building cellular taxonomies based on measurement of many phenotypic properties, as well as manipulate, moving beyond classification to understand the functional role of specific cell types and circuits in complex behaviors.
Effects of light-dark cycle on hippocampal iNOS expression and CREB activation in rats.
The Chinese journal of physiology, 2015

Nitric oxide (NO) is one of the most important interneural signaling molecules mediating hippocampal functions for learning and memory. The diurnal expression of neuronal NO synthase (nNOS) has been well studied. However, the temporal profile and underlying mechanisms of inducible NOS (iNOS) expression in a normal photoperiod or in altered light-dark cycles remain unclear. We examined the temporal profile of iNOS expression in adult male Sprague-Dawley rats maintained in a 12h-light/ 12h-dark photoperiod (12L/12D), which were pre-synchronized for 7 days before the experiment. The protein and mRNA levels of iNOS in the cortex and hippocampus were measured to examine the photic influences on iNOS expression. The results showed rhythmically changes of the levels of iNOS mRNA and protein in the hippocampus, but not in the cerebral cortex. The iNOS mRNA levels peaked at Zeitgeber time (ZT) 6 and ZT22, and the protein levels peaked at ZT8 and ZT18. Notably, the peaks in iNOS mRNA and protein levels in the 12L/12D group were 10 to 12 h apart, and the rhythmic pattern was absent in the 24-h period of the darkness group. In addition, the level of the phosphorylated cAMP response element binding protein (phospho-CREB) was the highest at ZT18, prior to a peak in iNOS mRNA expression at ZT22. A phospho-CREB-iNOS signaling pathway was further confirmed by the interaction of phospho-CREB and the iNOS DNA in histone complexes isolated by chromatin immunoprecipitation at ZT18. In conclusion, the photoperiod affects the diurnal expression of iNOS and activation of CREB in the hippocampus, which provide clues for the possible impact of circadian changes in hippocampal functions.
Evidence for a role of endocannabinoids, astrocytes and p38 phosphorylation in the resolution of postoperative pain.
PloS one, 2010

An alarming portion of patients develop persistent or chronic pain following surgical procedures, but the mechanisms underlying the transition from acute to chronic pain states are not fully understood. In general, endocannabinoids (ECBs) inhibit nociceptive processing by stimulating cannabinoid receptors type 1 (CB(1)) and type 2 (CB(2)). We have previously shown that intrathecal administration of a CB(2) receptor agonist reverses both surgical incision-induced behavioral hypersensitivity and associated over-expression of spinal glial markers. We therefore hypothesized that endocannabinoid signaling promotes the resolution of acute postoperative pain by modulating pro-inflammatory signaling in spinal cord glial cells.
Differential Effects of Deep Brain Stimulation of the Internal Capsule and the Striatum on Excessive Grooming in Sapap3 Mutant Mice.
Biological psychiatry, 2018

Deep brain stimulation (DBS) is an effective treatment for patients with obsessive-compulsive disorder (OCD) that do not respond to conventional therapies. Although the precise mechanism of action of DBS remains unknown, modulation of activity in corticofugal fibers originating in the prefrontal cortex is thought to underlie its beneficial effects in OCD.
Patterns of care and survival of glioblastoma patients: a comparative study between 2004 and 2008 in Lyon, France.
Revue neurologique, 2014

The treatment of glioblastomas (GBMs) has changed significantly since 2005. However, the extent to which this change has improved overall survival (OS) of patients treated outside clinical trials remains to be determined.
Whole-brain patterns of the presynaptic inputs and axonal projections of BDNF neurons in the paraventricular nucleus.
Journal of genetics and genomics = Yi chuan xue bao, 2019

Brain-derived neurotrophic factor (BDNF) plays a crucial role in human obesity. Yet, the neural circuitry supporting the BDNF-mediated control of energy homeostasis remains largely undefined. To map key regions that might provide inputs to or receive inputs from the paraventricular nucleus (PVN) BDNF neurons, a key type of cells in regulating feeding and thermogenesis, we used rabies virus-based transsynaptic labeling and adeno-associated virus based anterograde tracing techniques to reveal their whole-brain distributions. We found that dozens of brain regions provide dense inputs to or receive dense inputs from PVN BDNF neurons, including several known weight control regions and several novel regions that might be functionally important for the BDNF-mediated regulation of energy homeostasis. Interestingly, several regions show very dense reciprocal connections with PVN BDNF neurons, including the lateral septum, the preoptic area, the ventromedial hypothalamic nucleus, the paraventricular thalamic nucleus, the zona incerta, the lateral parabrachial nucleus, the subiculum, the raphe magnus nucleus, and the raphe pallidus nucleus. These strong anatomical connections might be indicative of important functional connections. Therefore, we provide an outline of potential neural circuitry mediated by PVN BDNF neurons, which might be helpful to resolve the complex obesity network.
Enhanced ATP release and CD73-mediated adenosine formation sustain adenosine A
British journal of pharmacology, 2019

Parkinson's disease (PD) involves an initial loss of striatal dopamine terminals evolving into degeneration of dopamine neurons in substantia nigra (SN), which can be modelled by 6-hydroxydopamine (6-OHDA) administration. Adenosine A
Chewing rescues stress-suppressed hippocampal long-term potentiation via activation of histamine H1 receptor.
Neuroscience research, 2009

We have previously found in rats that chewing, an active behavioral strategy to cope with a stressful situation, rescues long-term potentiation (LTP) in the hippocampus through activating stress-suppressed N-methyl-D-aspartate (NMDA) receptor function. To further examine the mechanisms underlying this ameliorative effect of chewing, we studied the involvement of the histaminergic system, which has been shown to be activated by mastication, in the LTP of hippocampal slices of rats that were allowed to chew a wooden stick during exposure to immobilization stress. Chewing failed to rescue stress-suppressed LTP in the rats treated with histamine H1 receptor (H1R) antagonist pyrilamine (5 mg/kg, i.p.) before exposure to stress, although administration of pyrilamine did not affect LTP in naive rats and in stressed rats that did not chew. However, when pyrilamine was administrated immediately after exposure to stress, chewing rescued LTP whose magnitude was statistically comparable to that in the rats that chewed without drug treatment. These results suggest that chewing-induced histamine release in the hippocampus and the subsequent H1 receptor activation may be essential to rescue stress-suppressed synaptic plasticity.
Quality of life of patients who undergo breast reconstruction after mastectomy: effects of personality characteristics.
Plastic and reconstructive surgery, 2011

Reconstruction after mastectomy has become an integral part of breast cancer treatment. The effects of psychological factors on quality of life after reconstruction have been poorly investigated. The authors examined clinical and personality characteristics related to quality of life in patients receiving reconstructive surgery.
Sustained activation of ERK1/2 MAPK in oligodendrocytes and schwann cells enhances myelin growth and stimulates oligodendrocyte progenitor expansion.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013

Myelin is a biologically active membrane receiving and processing signals from axons. Although much is known about its structure and molecular composition, the intracellular signal transduction pathways, active during specific phases of myelinogenesis for regulating myelin formation, remain poorly understood. Recent genetic loss-of-function studies have suggested a key role of extracelluar signal-regulated kinases-1 and -2 (ERK1/2), downstream mediators of mitogen-activated protein kinases (MAPKs), in promoting CNS and PNS myelination. In contrast, other studies, largely in vitro, have suggested that activation of ERK1/2 pathway can be detrimental for glial cell function and myelination. Given these conflicting reports, we investigated the effects of cell-autonomous activation of ERK1/2 in glial cells during developmental myelination in the intact CNS and PNS. Two lines of transgenic mice with sustained activation of ERK1/2 in oligodendrocyte progenitors (OPCs), oligodendrocytes, and Schwann cells were generated. Consistent with our loss-of-function studies, gain of ERK1/2 function in oligodendrocyte-lineage cells significantly increased myelin thickness, independent of oligodendrocyte differentiation or initiation of myelination. Additionally, increased activation of ERK1/2 in OPCs during early development resulted in transient hyperproliferation and overproduction of OPCs but generation of normal numbers of myelinating oligodendrocytes. Thus, these in vivo studies suggest a beneficial biphasic requirement of ERK1/2 during developmental myelination in the CNS, deployed first during early stages of the oligodendrocyte lineage for promoting OPC expansion and then redeployed later in myelinating oligodendrocytes for promoting myelin growth. Furthermore, Schwann cells with activated ERK1/2 hypermyelinate PNS axons, suggesting that ERK1/2 signaling is a conserved mechanism that promotes both CNS and PNS developmental myelination.
Phase-synchrony evaluation of EEG signals for Multiple Sclerosis diagnosis based on bivariate empirical mode decomposition during a visual task.
Computers in biology and medicine, 2020

Despite the widespread prevalence of Multiple Sclerosis (MS), the study of brain interactions is still poorly understood. Moreover, there has always been a great need to automate the MS diagnosis procedure to eliminate the evaluation errors thereby improving its consistency and reliability. To address these issues, in this work, we proposed a robust pattern recognition algorithm as a computer-aided diagnosis system. This method is based on calculating the pairwise phase-synchrony of EEG recordings during a visual task. Initially, the bivariate empirical mode decomposition (BEMD) was applied to extract the intrinsic mode functions (IMFs). The phases of these IMFs were then obtained using the Hilbert transform to be utilized in the mean phase coherence (MPC), a measure for phase-synchrony calculation. After the construction of the feature space using MPC values, the ReliefF algorithm was applied for dimension reduction. Finally, the best distinguishing features were input to a k-nearest neighbor (KNN) classifier. The results revealed a higher level of network synchronization in the posterior regions of the brain and desynchronization in the anterior regions among the MS group as compared with the normal subjects. In the validation phase, the leave-one-subject-out cross-validation (LOOCV) method was used to assess the validity of the proposed algorithm. We achieved an accuracy, sensitivity, and specificity of 93.09%, 91.07%, and 95.24% for red-green, 90.44%, 88.39%, and 92.62% for luminance, and 87.44%, 87.05%, and 87.86% for blue-yellow tasks, respectively. The experimental results demonstrated the reliability of the presented method to be generalized in the field of automated MS diagnosis systems.
Helix breaking transition in the S4 of HCN channel is critical for hyperpolarization-dependent gating.
eLife, 2019

In contrast to most voltage-gated ion channels, hyperpolarization- and cAMP gated (HCN) ion channels open on hyperpolarization. Structure-function studies show that the voltage-sensor of HCN channels are unique but the mechanisms that determine gating polarity remain poorly understood. All-atom molecular dynamics simulations (~20 μs) of HCN1 channel under hyperpolarization reveals an initial downward movement of the S4 voltage-sensor but following the transfer of last gating charge, the S4 breaks into two sub-helices with the lower sub-helix becoming parallel to the membrane. Functional studies on bipolar channels show that the gating polarity strongly correlates with helical turn propensity of the substituents at the breakpoint. Remarkably, in a proto-HCN background, the replacement of breakpoint serine with a bulky hydrophobic amino acid is sufficient to completely flip the gating polarity from inward to outward-rectifying. Our studies reveal an unexpected mechanism of inward rectification involving a linker sub-helix emerging from HCN S4 during hyperpolarization.
Mild cognitive impairment and sedentary behavior: A multinational study.
Experimental gerontology, 2018

Sedentary behavior (SB) is associated with poor cognitive performance. However, the contribution of sedentary time to risk of mild cognitive impairment (MCI) remains unclear. This study assessed the association of SB with MCI in six low- and middle-income countries.
Senile Dementia from Neuroscientific and Islamic Perspectives.
Journal of religion and health, 2018

Diseases involving the nervous system drastically change lives of victims and commonly increase dependency on others. This paper focuses on senile dementia from both the neuroscientific and Islamic perspectives, with special emphasis on the integration of ideas between the two different disciplines. This would enable effective implementation of strategies to address issues involving this disease across different cultures, especially among the world-wide Muslim communities. In addition, certain incongruence ideas on similar issues can be understood better. The former perspective is molded according to conventional modern science, while the latter on the analysis of various texts including the holy Qur'an, sunnah [sayings and actions of the Islamic prophet, Muhammad (pbuh)] and writings of Islamic scholars. Emphasis is particularly given on causes, symptoms, treatments and prevention of dementia.