Search results for " inhibition"
showing 10 items of 435 documents
Characterization of somatostatin- and cholecystokinin-immunoreactive periglomerular cells in the rat olfactory bulb.
2005
Periglomerular cells (PG) are interneurons of the olfactory bulb (OB) that modulate the first synaptic relay of the olfactory information from the olfactory nerve to the dendrites of the bulbar principal cells. Previous investigations have pointed to the heterogeneity of these interneurons and have demonstrated the presence of two different types of PG. In the rat OB, type 1 PG receive synaptic contacts from the olfactory axons and are γ-aminobutyric acid (GABA)-ergic, whereas type 2 PG do not receive synaptic contacts from the olfactory axons and are GABA immunonegative. In this study, we analyze and characterize neurochemically a group of PG that has not been previously classified either …
Nitric oxide synthase containing periglomerular cells are GABAergic in the rat olfactory bulb.
2003
In the olfactory glomeruli of the rat olfactory bulb, there is a population of periglomerular cells (PG) that contains the neuronal isoform of the nitric oxide synthase (nNOS). To date, these PG have not been characterized neurochemically and it has not been determined whether they are type 1 (GABAergic PG that receive synaptic contacts from the olfactory axons) or type 2 PG (non-GABAergic PG that do not receive synapses from the olfactory axons). Combining pre-embedding NADPH-diaphorase histochemistry and post-embedding immunoperoxidase detection of GABA, we demonstrate that nNOS-containing PG are GABAergic and therefore, belong to the type 1 PG. The possible actions of nitric oxide in the…
Mechanisms of Raf-1 Kinase Inhibitor Protein Dysregulation in Triple-Negative Breast Cancers and Identification of Possible Novel Therapeutic Approac…
2014
Triple-negative breast cancers (TNBCs) are a heterogenous group of breast cancers characterized by poor prognosis because they are not amenable to targeted therapies. We have taken into account that altered expression of Raf-1 kinase inhibitor protein (RKIP), a tumor and metastasis suppressor and a promoter of drug-induced apoptosis, is frequent in TNBCs and may be involved in their aggressive biology. Interestingly, the analysis of the possible mechanisms of RKIP downregulation in TNBCs permits the identification and recapitulation of different possible approaches, including epigenetic modulation, e.g., by DNA demethylating agents or histone deacetylase inhibition, and NF-κB inhibition. Th…
Job skill discretion and emotion control strategies as antecedents of recovery from work
2014
Recovery from work protects employees’ health and well-being, and therefore it is important to understand its antecedents. The aim of this study conducted among 183 middle-aged participants drawn from the Finnish Jyvaskyla Longitudinal Study of Personality and Social Development was to examine whether job skill discretion and emotion control strategies (emotional rumination and emotional inhibition) are related to psychological aspects of recovery from work (subjective recovery evaluation, psychological detachment and relaxation). The results of hierarchical general linear models confirmed the hypothesis that job skill discretion is positively associated with subjective recovery evaluation …
MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate
2019
Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1…
Endoplasmic Reticulum Stress Inhibition Protects against Excitotoxic Neuronal Injury in the Rat Brain
2007
Elevated brain glutamate with activation of neuronal glutamate receptors accompanies neurological disorders, such as epilepsy and brain trauma. However, the mechanisms by which excitotoxicity triggers neuronal injury are not fully understood. We have studied the glutamate receptor agonist kainic acid (KA) inducing seizures and excitotoxic cell death. KA caused the disintegration of the endoplasmic reticulum (ER) membrane in hippocampal neurons and ER stress with the activation of the ER proteins Bip, Chop, and caspase-12. Salubrinal, inhibiting eIF2α (eukaryotic translation initiation factor 2 subunit α) dephosphorylation, significantly reduced KA-induced ER stress and neuronal deathin vivo…
Development of natural and synthetic compounds as kinase inhibitors targeting cancer cells and cancer stem cells
2023
Modelling the spatial and temporal constrains of the GABAergic influence on neuronal excitability
2021
GABA (γ-amino butyric acid) is an inhibitory neurotransmitter in the adult brain that can mediate depolarizing responses during development or after neuropathological insults. Under which conditions GABAergic membrane depolarizations are sufficient to impose excitatory effects is hard to predict, as shunting inhibition and GABAergic effects on spatiotemporal filtering of excitatory inputs must be considered. To evaluate at which reversal potential a net excitatory effect was imposed by GABA (EGABAThr), we performed a detailed in-silico study using simple neuronal topologies and distinct spatiotemporal relations between GABAergic and glutamatergic inputs. These simulations revealed for GABAe…
Effect of depolarizing GABAA-mediated membrane responses on excitability of Cajal-Retzius cells in the immature rat neocortex
2011
In immature neurons activation of ionotropic GABA receptors induces depolarizing membrane responses due to a high intracellular Cl− concentration ([Cl−]i). However, it is difficult to draw conclusions about the functional consequences of subthreshold GABAergic depolarizations, since GABAergic membrane shunting and additional effects on voltage-dependent ion channels or action potential threshold must be considered. To systematically investigate factors that determine the GABAergic effect on neuronal excitability we performed whole cell patch-clamp recordings from Cajal-Retzius cells in immature rat neocortex, using [Cl−]i between 10 and 50 mM. The effect of focal GABA application was quant…