Search results for "Potential"
showing 10 items of 3348 documents
Neural oscillations in the infralimbic cortex after electrical stimulation of the amygdala. Relevance to acute stress processing
2017
The stress system coordinates the adaptive reactions of the organism to stressors. Therefore, dysfunctions in this circuit may correlate to anxiety-related disorders, including depression. Comprehending the dynamics of this network may lead to a better understanding of the mechanisms that underlie these diseases. The central nucleus of the amygdala (CeA) activates the hypothalamic–pituitary–adrenal axis and brainstem nodes by triggering endocrine, autonomic and behavioral stress responses. The medial prefrontal cortex plays a significant role in regulating reactions to stressors, and is specifically important for limiting fear responses. Brain oscillations reflect neural systems activity. S…
Extrinsic and intrinsic mechanisms of axon regeneration: the need for spinal cord injury treatment strategies to address both
2016
Spinal cord injury (SCI) causes disturbances in motor and sensory functions leading to paralysis, the severity of which depends on the spinal level of the injury. Traumatic lesions of spinal cord axon projection tracts are untreatable in human patients, although numerous research groups worldwide are studying putative treatment strategies. Both extrinsic factors in the environment of the axons as well as intrinsic factors in the neurons themselves play important roles in the regeneration process (Chew et al., 2012). The peripheral nervous system (PNS) provides a good example where the extrinsic and intrinsic factors play optimally together to allow regeneration. Schwann cells dedifferentiat…
Loss of MCL1 function sensitizes the MDA-MB-231 breast cancer cells to rh-TRAIL by increasing DR4 levels.
2019
Triple-negative breast cancer (TNBC) is a form of BC characterized by high aggressiveness and therapy resistance probably determined by cancer stem cells. MCL1 is an antiapoptotic Bcl-2 family member that could limit the efficacy of anticancer agents as recombinant human tumor necrosis factor related apoptosis-inducing ligand (rh-TRAIL). Here, we investigated MCL1 expression in TNBC tissues and cells. We found MCL1 differentially expressed (upregulated or downregulated) in TNBC tissues. Furthermore, in comparison to the human mammary epithelial cells, we found that MDA-MB-231 cells show similar messenger RNA levels but higher MCL1 protein levels, whereas it resulted downregulated in MDA-MB-…
Disruption of otoferlin alters the mode of exocytosis at the mouse inner hair cell ribbon synapse
2019
Sound encoding relies on Ca2+-mediated exocytosis at the ribbon synapse between cochlear inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs). Otoferlin, a multi-C-2 domain protein, is proposed to regulate Ca2+-triggered exocytosis at this synapse, but the precise mechanisms of otoferlin function remain to be elucidated. Here, performing whole-cell voltage-clamp recordings of excitatory postsynaptic currents (EPSCs) from SGNs in otoferlin mutant mice, we investigated the impact of Otof disruption at individual synapses with single release event resolution. Otof deletion decreased the spontaneous release rate and abolished the stimulus-secretion coupling. This was evident from f…
Dysregulated Prefrontal Cortex Inhibition in Prepubescent and Adolescent Fragile X Mouse Model
2020
Changes in excitation and inhibition are associated with the pathobiology of neurodevelopmental disorders of intellectual disability and autism and are widely described in Fragile X syndrome (FXS). In the prefrontal cortex (PFC), essential for cognitive processing, excitatory connectivity and plasticity are found altered in the FXS mouse model, however, little is known about the state of inhibition. To that end, we investigated GABAergic signaling in the Fragile X Mental Retardation 1 (FMR1) knock out (Fmr1-KO) mouse medial PFC (mPFC). We report changes at the molecular, and functional levels of inhibition at three (prepubescence) and six (adolescence) postnatal weeks. Functional changes we…
Neuroactive Steroids Reverse Tonic Inhibitory Deficits in Fragile X Syndrome Mouse Model
2018
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. A reduction in neuronal inhibition mediated by γ-aminobutyric acid type A receptors (GABAARs) has been implicated in the pathophysiology of FXS. Neuroactive steroids (NASs) are known allosteric modulators of GABAAR channel function, but recent studies from our laboratory have revealed that NASs also exert persistent metabotropic effects on the efficacy of tonic inhibition by increasing the protein kinase C (PKC)-mediated phosphorylation of the α4 and β3 subunits which increase the membrane expression and boosts tonic inhibition. We have assessed the GABAergic signaling in the hippocampus of fragile X ment…
Coincident Activation of Glutamate Receptors Enhances GABAA Receptor-Induced Ionic Plasticity of the Intracellular Cl−-Concentration in Dissociated N…
2019
Massive activation of γ-amino butyric acid A (GABAA) receptors during pathophysiological activity induces an increase in the intracellular Cl−-concentration ([Cl−]i), which is sufficient to render GABAergic responses excitatory. However, to what extent physiological levels of GABAergic activity can influence [Cl−]i is not known. Aim of the present study is to reveal whether moderate activation of GABAA receptors mediates functionally relevant [Cl−]i changes and whether these changes can be augmented by coincident glutamatergic activity. To address these questions, we used whole-cell patch-clamp recordings from cultured cortical neurons [at days in vitro (DIV) 6–22] to determine changes in t…
Cytoprotective Effects of Dinitrosyl Iron Complexes on Viability of Human Fibroblasts and Cardiomyocytes
2019
Nitric oxide (NO) is an important signaling molecule that plays a key role in maintaining vascular homeostasis. Dinitrosyl iron complexes (DNICs) generating NO are widely used to treat cardiovascular diseases. However, the involvement of DNICs in the metabolic processes of the cell, their protective properties in doxorubicin-induced toxicity remain to be clarified. Here, we found that novel class of mononuclear DNICs with functional sulfur-containing ligands enhanced the cell viability of human lung fibroblasts and rat cardiomyocytes. Moreover, DNICs demonstrated remarkable protection against doxorubicin-induced toxicity in fibroblasts and in rat cardiomyocytes (H9c2 cells). Data revealed t…
Nitric oxide/cGMP signaling via guanylyl cyclase isoform 1 modulates glutamate and GABA release in somatosensory cortex of mice
2017
Abstract In hippocampus, two guanylyl cyclases (NO-GC1 and NO-GC2) are involved in the transduction of the effects of nitric oxide (NO) on synaptic transmission. However, the respective roles of the NO-GC isoforms on synaptic transmission are less clear in other regions of the brain. In the present study, we used knock-out mice deficient for the NO-GC1 isoform (NO-GC1 KO) to analyze its role in the glutamatergic and GABAergic neurotransmission at pyramidal neurons in layers II/III of somatosensory cortex. NO-GC1 KO slices revealed reduced frequencies of miniature excitatory- and inhibitory-postsynaptic currents, increased paired-pulse ratios and decreased input–output curves of evoked signa…
The Severity of Acute Stress Is Represented by Increased Synchronous Activity and Recruitment of Hypothalamic CRH Neurons
2016
The hypothalamo-pituitary-adrenocortical (HPA) axis regulates stress physiology and behavior. To achieve an optimally tuned adaptive response, it is critical that the magnitude of the stress response matches the severity of the threat. Corticotropin-releasing hormone (CRH) released from the paraventricular nucleus of the hypothalamus is a major regulator of the HPA axis. However, how CRH-producing neurons in an intact animal respond to different stressor intensities is currently not known. Using two-photon calcium imaging on intact larval zebrafish, we recorded the activity of CRH cells, while the larvae were exposed to stressors of varying intensity. By combining behavioral and physiologic…