Striatal astrocytic A2A-D2 receptor-receptor interactions and their role in neuropsychiatric disorders

Neuropharmacology, Journal Year: 2023, Volume and Issue: 237, P. 109636 - 109636

Published: June 15, 2023

It is now generally accepted that astrocytes are active players in synaptic transmission, so a neurocentric perspective of the integrative signal communication central nervous system shifting towards neuro-astrocentric perspective. Astrocytes respond to activity, release chemical signals (gliotransmitters) and express neurotransmitter receptors (G protein-coupled ionotropic receptors), thus behaving as co-actors with neurons system. The ability G physically interact through heteromerization, forming heteromers receptor mosaics new distinct recognition transduction pathways, has been intensively studied at neuronal plasma membrane, changed view One best-known examples receptor-receptor interaction relevant consequences for both physiological pharmacological points view, given by adenosine A2A dopamine D2 on membrane striatal neurons. Here we review evidence native can heteromerization well. Astrocytic A2A-D2 were found able control glutamate from astrocyte processes. processes discussed far their potential relevance glutamatergic transmission striatum concerned, including roles dysregulation pathological conditions schizophrenia or Parkinson's disease.

Language: Английский

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Oxytocin, GABA, and dopamine interplay in autism

Endocrine Regulations, Journal Year: 2024, Volume and Issue: 58(1), P. 105 - 114

Published: Jan. 1, 2024

Oxytocin plays an important role in brain development and is associated with various neurotransmitter systems the brain. Abnormalities production, secretion, distribution of oxytocin brain, at least during some stages development, are critical for pathogenesis neuropsychiatric diseases, particularly autism spectrum disorder. The etiology includes changes local sensory dopaminergic areas which also supplied by hypothalamic sources oxytocin. It very to understand their mutual relationship. In this review, relationship several components system, gamma-aminobutyric acid (GABA) inhibitory neurotransmission alterations disorder discussed. Special attention has been paid results describing a reduced expression GABAergic markers context models autism. presumed that altered neurotransmission, due absence or dysfunction certain developmental stages, disinhibits signaling contributes symptoms.

Language: Английский

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Chemogenetic Control of Striatal Astrocytes Improves Parkinsonian Motor Deficits in Mice

Glia, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

ABSTRACT Parkinson's disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal inputs, which causes striatal network dysfunction and leads to pronounced motor deficits. Recent evidence highlights astrocytes as a potential local source for neuromodulation. There substantial norepinephrine‐mediated recruitment cortical astrocyte activity during movement locomotion. However, it unclear how in striatum, region devoid norepinephrine neuromodulatory respond Moreover, remains unknown dopamine loss affects whether regulates behavioral deficits PD. We addressed these questions performing astrocyte‐specific calcium recordings manipulations using vivo fiber photometry chemogenetics. find that locomotion elicits over slower timescale than neurons. Acute pharmacological blockade receptors only moderately reduced locomotion‐related activity. Yet, unilateral depletion significantly attenuated responses. Chemogenetic stimulation G i ‐coupled partially improved this functional deficit dopamine‐lesioned mice. In parallel, chemogenetic manipulation restored asymmetrical open‐field exploratory behavior. Together, our results establish novel role signaling modulating function PD highlight non‐neuronal targets therapeutics.

Language: Английский

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Emerging therapeutic landscape on delivery of oxytocin to brain for treating neurological disorders

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 92, P. 105370 - 105370

Published: Jan. 12, 2024

Language: Английский

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Modulation of Neuron and Astrocyte Dopamine Receptors via Receptor–Receptor Interactions

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(10), P. 1427 - 1427

Published: Oct. 8, 2023

Dopamine neurotransmission plays critical roles in regulating complex cognitive and behavioral processes including reward, motivation, reinforcement learning, movement. receptors are classified into five subtypes, widely distributed across the brain, regions responsible for motor functions specific areas related to emotional functions. also acts on astrocytes, which express dopamine as well. The discovery of direct receptor–receptor interactions, leading formation multimeric receptor complexes at cell membrane providing decoding apparatus with flexible dynamics terms recognition signal transduction, has expanded knowledge G-protein-coupled receptor-mediated signaling processes. purpose this review article is provide an overview currently identified containing their modulatory action dopamine-mediated between neurons astrocytes. Pharmacological possibilities offered by targeting addressing neuropsychiatric disorders associated altered will be briefly discussed.

Language: Английский

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The role of intraamygdaloid oxytocin in spatial learning and avoidance learning

Peptides, Journal Year: 2024, Volume and Issue: 175, P. 171169 - 171169

Published: Feb. 9, 2024

The goal of the present study is to investigate role intraamygdaloid oxytocin in learning-related mechanisms. Oxytocin a neuropeptide which involved social bonding, trust, emotional responses and various behaviors. By conducting passive avoidance Morris water maze tests on male Wistar rats, memory performance learning was investigated. doses 10 ng 100 were injected into central nucleus amygdala. Our results showed that significantly reduced time required locate platform during test while increasing latency test. However, experiment failed produce significant effect either tests. rats pretreated with 20 receptor antagonist (L-2540) administered amygdala also subjected aforementioned highlight receptors spatial- learning. Results suggest supports processing both antagonists can however block effects substantiate uses enhance performance.

Language: Английский

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Moxie begets MOXI: The journey to a novel hypothesis about Mu-opioid and OXytocin system Interactions

Comprehensive Psychoneuroendocrinology, Journal Year: 2024, Volume and Issue: 19, P. 100244 - 100244

Published: June 26, 2024

This narrative review summarizes the early life of author, Khalin E. Nisbett, and highlights factors that led to her career in research development two novel hypotheses:

Language: Английский

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Functional activation of dorsal striatum astrocytes improves movement deficits in hemi-parkinsonian mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 2, 2024

Summary Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal inputs, which causes striatal network dysfunction and leads to pronounced motor deficits. Recent evidence highlights astrocytes as a potential local source modulation. However, it remains unknown how dopamine loss affects astrocyte activity whether regulates behavioral deficits in PD. We addressed these questions performing astrocyte-specific calcium recordings manipulations using vivo fiber photometry chemogenetics. find that locomotion elicits over slower timescale than neurons. Unilateral depletion reduced locomotion-related responses. Chemogenetic activation facilitated activity, improved asymmetrical open field exploratory behavior lesioned mice. Together, our results establish novel role for functional signaling modulating function PD highlight non-neuronal targets therapeutics.

Language: Английский

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Control of Dopamine Signal in High-Order Receptor Complex on Striatal Astrocytes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8610 - 8610

Published: Aug. 7, 2024

The receptor-receptor interaction (RRI) of G protein-coupled receptors (GPCRs) leads to new functional entities that are conceptually distinct from the simple addition signals mediated by activation form heteromers. Focusing on astrocytes, there is evidence for existence inhibitory and facilitatory RRIs, including heteromers formed adenosine A2A dopamine D2 receptors, oxytocin receptor (OTR), D2-OTR possible involvement these in mosaicism has never been investigated striatal astrocytes. By biophysical approaches, we focused our attention an A2A-D2-OTR high-order complex its role modulating cytosolic calcium levels endogenous glutamate release, when astrocyte processes were stimulated with 4-aminopyridine. Functional data indicate a permissive OTR signaling regulation glutamatergic transmission, control both D2-mediated OTR-facilitating effect D2. Imaging biochemical bioinformatic confirmed ternary structure membrane. In conclusion, appears be hotspot release astrocytic may contribute integration different neurotransmitter-mediated striatum heterotrimers. Considering selectivity allosteric interventions GPCRs organized as mosaics, heterotrimers offer selective pharmacological targets neuropsychiatric disorders neurodegenerative diseases.

Language: Английский

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Possible roles of heteroreceptor complexes in excitotoxic processes

Exploration of Neuroprotective Therapy, Journal Year: 2024, Volume and Issue: 4(5), P. 366 - 391

Published: Sept. 24, 2024

Excitotoxicity represents a neuropathological process, describing the toxic actions of excitatory neurotransmitters, where excessive or prolonged activation glutamate receptors triggers cascade events leading to neuronal injury death. Under conditions reduced energy availability and increased oxidative stress neurons become particularly vulnerable excitotoxicity large body available evidence indicates that central mechanism in pathogenesis acute degenerative diseases nervous system. Astrocytes represent key elements regulation homeostasis by their opposing functions uptake release, microglial cells play an important role response damage. Depending on phenotype they assume when activated, can trigger immune defense neuroprotective processes. To perform both glial cell populations monitor extracellular space through panel receptors. Furthermore, variety signaling pathways also contribute modulation glutamatergic transmission, acting specific expressed neurons, astrocytes, microglia. In last decades, has been provided almost all families establish structural receptor-receptor interactions, formation heteroreceptor complexes at membrane cells. The cooperativity emerges ligands monomers forming these assemblies provides decoding apparatus with flexible dynamics terms recognition signal transduction allows integration incoming signals already level. Available data possible modulatory roles played excitotoxic processes will be here reviewed discussed. From pharmacological standpoint, findings may offer possibilities explore novel therapeutic strategies targeting receptor address disorders system associated dysregulation signaling.

Language: Английский

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