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Current Neuropharmacology 2018Antipsychotic-induced metabolic side effects are major concerns in psychopharmacology and clinical psychiatry. Their pathogenetic mechanisms are still not elucidated. (Review)
Review
BACKGROUND
Antipsychotic-induced metabolic side effects are major concerns in psychopharmacology and clinical psychiatry. Their pathogenetic mechanisms are still not elucidated.
METHODS
Herein, we review the impact of neurotransmitters on metabolic regulation, providing insights into antipsychotic-induced metabolic side effects.
RESULTS
Antipsychotic drugs seem to interfere with feeding behaviors and energy balance, processes that control metabolic regulation. Reward and energy balance centers in central nervous system constitute the central level of metabolic regulation. The peripheral level consists of skeletal muscles, the liver, the pancreas, the adipose tissue and neuroendocrine connections. Neurotransmitter receptors have crucial roles in metabolic regulation and they are also targets of antipsychotic drugs. Interaction of antipsychotics with neurotransmitters could have both protective and harmful effects on metabolism.
CONCLUSION
Emerging evidence suggests that antipsychotics have different liabilities to induce obesity, diabetes and dyslipidemia. However this diversity cannot be explained merely by drugs'pharmacodynamic profiles, highlighting the need for further research.
Topics: Animals; Antipsychotic Agents; Humans; Metabolic Diseases; Receptors, Neurotransmitter
PubMed: 28676017
DOI: 10.2174/1570159X15666170630163616 -
Alcohol Research & Health : the Journal... 2008Nerve cells (i.e., neurons) communicate via a combination of electrical and chemical signals. Within the neuron, electrical signals driven by charged particles allow... (Review)
Review
Nerve cells (i.e., neurons) communicate via a combination of electrical and chemical signals. Within the neuron, electrical signals driven by charged particles allow rapid conduction from one end of the cell to the other. Communication between neurons occurs at tiny gaps called synapses, where specialized parts of the two cells (i.e., the presynaptic and postsynaptic neurons) come within nanometers of one another to allow for chemical transmission. The presynaptic neuron releases a chemical (i.e., a neurotransmitter) that is received by the postsynaptic neuron's specialized proteins called neurotransmitter receptors. The neurotransmitter molecules bind to the receptor proteins and alter postsynaptic neuronal function. Two types of neurotransmitter receptors exist-ligand-gated ion channels, which permit rapid ion flow directly across the outer cell membrane, and G-protein-coupled receptors, which set into motion chemical signaling events within the cell. Hundreds of molecules are known to act as neurotransmitters in the brain. Neuronal development and function also are affected by peptides known as neurotrophins and by steroid hormones. This article reviews the chemical nature, neuronal actions, receptor subtypes, and therapeutic roles of several transmitters, neurotrophins, and hormones. It focuses on neurotransmitters with important roles in acute and chronic alcohol effects on the brain, such as those that contribute to intoxication, tolerance, dependence, and neurotoxicity, as well as maintained alcohol drinking and addiction.
Topics: Alcoholism; Animals; Brain; Humans; Neurons; Neurotransmitter Agents; Receptors, G-Protein-Coupled; Receptors, Neurotransmitter; Synapses
PubMed: 23584863
DOI: No ID Found -
Proceedings of the National Academy of... Feb 2020Synaptic communication requires the expression of functional postsynaptic receptors that match the presynaptically released neurotransmitter. The ability of neurons to...
Synaptic communication requires the expression of functional postsynaptic receptors that match the presynaptically released neurotransmitter. The ability of neurons to switch the transmitter they release is increasingly well documented, and these switches require changes in the postsynaptic receptor population. Although the activity-dependent molecular mechanism of neurotransmitter switching is increasingly well understood, the basis of specification of postsynaptic neurotransmitter receptors matching the newly expressed transmitter is unknown. Using a functional assay, we show that sustained application of glutamate to embryonic vertebrate skeletal muscle cells cultured before innervation is necessary and sufficient to up-regulate ionotropic glutamate receptors from a pool of different receptors expressed at low levels. Up-regulation of these ionotropic receptors is independent of signaling by metabotropic glutamate receptors. Both imaging of glutamate-induced calcium elevations and Western blots reveal ionotropic glutamate receptor expression prior to immunocytochemical detection. Sustained application of glutamate to skeletal myotomes in vivo is necessary and sufficient for up-regulation of membrane expression of the GluN1 NMDA receptor subunit. Pharmacological antagonists and morpholinos implicate p38 and Jun kinases and MEF2C in the signal cascade leading to ionotropic glutamate receptor expression. The results suggest a mechanism by which neuronal release of transmitter up-regulates postsynaptic expression of appropriate transmitter receptors following neurotransmitter switching and may contribute to the proper expression of receptors at the time of initial innervation.
Topics: Animals; Calcium; Female; Glutamic Acid; Mitogen-Activated Protein Kinase 8; Muscle Cells; Neurons; Neurotransmitter Agents; Receptors, N-Methyl-D-Aspartate; Synapses; Xenopus
PubMed: 32041885
DOI: 10.1073/pnas.1916600117 -
Nature Reviews. Neuroscience Jan 2012For many years it has been assumed that the identity of the transmitters expressed by neurons is stable and unchanging. Recent work, however, shows that electrical... (Review)
Review
For many years it has been assumed that the identity of the transmitters expressed by neurons is stable and unchanging. Recent work, however, shows that electrical activity can respecify neurotransmitter expression during development and in the mature nervous system, and an understanding is emerging of the molecular mechanisms underlying activity-dependent transmitter respecification. Changes in postsynaptic neurotransmitter receptor expression accompany and match changes in transmitter specification, thus enabling synaptic transmission. The functional roles of neurotransmitter respecification are beginning to be understood and appear to involve homeostatic synaptic regulation, which in turn influences behaviour. Activation of this novel form of plasticity by sensorimotor stimuli may provide clinical benefits.
Topics: Animals; Calcium Signaling; Cell Differentiation; Cell Movement; Homeostasis; Models, Biological; Motor Activity; Neurons; Neurotransmitter Agents; Receptors, Neurotransmitter; Synapses
PubMed: 22251956
DOI: 10.1038/nrn3154 -
Cells Dec 2020Many receptors for neurotransmitters, such as dopamine, norepinephrine, acetylcholine, and neuropeptides, belong to the superfamily of G protein-coupled receptors... (Review)
Review
Many receptors for neurotransmitters, such as dopamine, norepinephrine, acetylcholine, and neuropeptides, belong to the superfamily of G protein-coupled receptors (GPCRs). A general model posits that GPCRs undergo two-step homologous desensitization: the active receptor is phosphorylated by kinases of the G protein-coupled receptor kinase (GRK) family, whereupon arrestin proteins specifically bind active phosphorylated receptors, shutting down G protein-mediated signaling, facilitating receptor internalization, and initiating distinct signaling pathways via arrestin-based scaffolding. Here, we review the mechanisms of GRK-dependent regulation of neurotransmitter receptors, focusing on the diverse modes of GRK-mediated phosphorylation of receptor subtypes. The immediate signaling consequences of GRK-mediated receptor phosphorylation, such as arrestin recruitment, desensitization, and internalization/resensitization, are equally diverse, depending not only on the receptor subtype but also on phosphorylation by GRKs of select receptor residues. We discuss the signaling outcome as well as the biological and behavioral consequences of the GRK-dependent phosphorylation of neurotransmitter receptors where known.
Topics: Animals; Arrestins; G-Protein-Coupled Receptor Kinases; Humans; Phosphorylation; Receptors, G-Protein-Coupled; Receptors, Neurotransmitter; Signal Transduction
PubMed: 33396400
DOI: 10.3390/cells10010052 -
Invertebrate Neuroscience : IN Nov 2018Na/K-pump is an electrogenic transmembrane ATPase located in the outer plasma membrane of cells. The Na/K-ATPase pumps 3 sodium ions out of cells while pumping 2... (Review)
Review
Na/K-pump is an electrogenic transmembrane ATPase located in the outer plasma membrane of cells. The Na/K-ATPase pumps 3 sodium ions out of cells while pumping 2 potassium ions into cells. Both cations move against their concentration gradients. This enzyme's electrogenic nature means that it has a chronic role in stabilizing the resting membrane potential of the cell, in regulating the cell volume and in the signal transduction of the cell. This review will mainly consider the role of the Na/K-pump in neurons, with an emphasis on its role in modulating neurotransmitter receptor. Most of the literature on the modulation of neurotransmitter receptors refers to the situation in the mammalian nervous system, but the position is likely to be similar in most, if not all, invertebrate nervous systems.
Topics: Animals; Humans; Membrane Potentials; Neurons; Receptors, Neurotransmitter; Sodium-Potassium-Exchanging ATPase
PubMed: 30488358
DOI: 10.1007/s10158-018-0221-7 -
Scientific Reports Jun 2022In the weeks immediately after onset of sensory loss, extensive reorganization of both the cortex and hippocampus occurs. Two fundamental characteristics comprise...
In the weeks immediately after onset of sensory loss, extensive reorganization of both the cortex and hippocampus occurs. Two fundamental characteristics comprise widespread changes in the relative expression of GABA and glutamate receptors and debilitation of hippocampal synaptic plasticity. Here, we explored whether recovery from adaptive changes in the expression of plasticity-related neurotransmitter receptors and hippocampal synaptic plasticity occurs in the time-period of up to 12 months after onset of sensory loss. We compared receptor expression in CBA/J mice that develop hereditary blindness, with CBA/CaOlaHsd mice that have intact vision and no deficits in other sensory modalities throughout adulthood. GluN1-subunit expression was reduced and the GluN2A:GluN2B ratio was persistently altered in cortex and hippocampus. GABA-receptor expression was decreased and metabotropic glutamate receptor expression was altered. Hippocampal synaptic plasticity was persistently compromised in vivo. But although LTP in blind mice was chronically impaired throughout adulthood, a recovery of the early phase of LTP became apparent when the animals reached 12 months of age. These data show that cortical and hippocampal adaptation to early postnatal blindness progresses into advanced adulthood and is a process that compromises hippocampal function. A partial recovery of hippocampal synaptic plasticity emerges in advanced adulthood, however.
Topics: Animals; Blindness; Hippocampus; Mice; Mice, Inbred CBA; Neuronal Plasticity; Neurotransmitter Agents; Receptors, Neurotransmitter; gamma-Aminobutyric Acid
PubMed: 35650390
DOI: 10.1038/s41598-022-13127-y -
Nature Neuroscience Jul 2023Dynamics and functions of neural circuits depend on interactions mediated by receptors. Therefore, a comprehensive map of receptor organization across cortical regions...
Dynamics and functions of neural circuits depend on interactions mediated by receptors. Therefore, a comprehensive map of receptor organization across cortical regions is needed. In this study, we used in vitro receptor autoradiography to measure the density of 14 neurotransmitter receptor types in 109 areas of macaque cortex. We integrated the receptor data with anatomical, genetic and functional connectivity data into a common cortical space. We uncovered a principal gradient of receptor expression per neuron. This aligns with the cortical hierarchy from sensory cortex to higher cognitive areas. A second gradient, driven by serotonin 5-HT receptors, peaks in the anterior cingulate, default mode and salience networks. We found a similar pattern of 5-HT expression in the human brain. Thus, the macaque may be a promising translational model of serotonergic processing and disorders. The receptor gradients may enable rapid, reliable information processing in sensory cortical areas and slow, flexible integration in higher cognitive areas.
Topics: Aged; Animals; Female; Humans; Male; Rats; Autoradiography; Brain Mapping; Cerebral Cortex; Cognition; Dendritic Spines; Gyrus Cinguli; Macaca fascicularis; Rats, Inbred Lew; Receptor, Serotonin, 5-HT1A; Receptors, Cholinergic; Receptors, Dopamine; Receptors, Neurotransmitter; Serotonin; Species Specificity; Myelin Sheath
PubMed: 37336976
DOI: 10.1038/s41593-023-01351-2 -
Biomolecules Apr 2020The concept of pharmacological receptor was proposed at the turn of the 20th century but it took almost 70 years before the first receptor for a neurotransmitter was... (Review)
Review
The concept of pharmacological receptor was proposed at the turn of the 20th century but it took almost 70 years before the first receptor for a neurotransmitter was isolated and identified as a protein. This review retraces the history of the difficulties and successes in the identification of the nicotinic acetylcholine receptor, the first neurotransmitter receptor to be identified.
Topics: Animals; Drug Discovery; Humans; Receptors, Nicotinic
PubMed: 32260196
DOI: 10.3390/biom10040547 -
NeuroImage Dec 2022Neurotransmitter receptors modulate signaling between neurons. Thus, neurotransmitter receptors and transporters play a key role in shaping brain function. Due to the...
Neurotransmitter receptors modulate signaling between neurons. Thus, neurotransmitter receptors and transporters play a key role in shaping brain function. Due to the lack of comprehensive neurotransmitter receptor/transporter density datasets, microarray gene expression measuring mRNA transcripts is often used as a proxy for receptor densities. In the present report, we comprehensively test the spatial correlation between gene expression and protein density for a total of 27 neurotransmitter receptors, receptor binding-sites, and transporters across 9 different neurotransmitter systems, using both PET and autoradiography radioligand-based imaging modalities. We find poor spatial correspondences between gene expression and density for all neurotransmitter receptors and transporters except four single-protein metabotropic receptors (5-HT, CB, D, and MOR). These expression-density associations are related to gene differential stability and can vary between cortical and subcortical structures. Altogether, we recommend using direct measures of receptor and transporter density when relating neurotransmitter systems to brain structure and function.
Topics: Humans; Receptors, Neurotransmitter; Brain; Autoradiography; Neurotransmitter Agents; Carrier Proteins; Gene Expression
PubMed: 36209794
DOI: 10.1016/j.neuroimage.2022.119671