Engineering, Год журнала: 2024, Номер 44, С. 256 - 265
Опубликована: Дек. 25, 2024
Язык: Английский
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Март 17, 2024
Abstract Altered interaction between striatonigral dopaminergic (DA) inputs and local acetylcholine (ACh) in striatum has long been hypothesized to play a central role dystonia pathophysiology. Indeed, previous research across various genetic mouse models of human isolated identified as shared endophenotype with paradoxical excitation striatal cholinergic interneurons (ChIs) activity response activation dopamine D2 receptor (D2R). These lack dystonic motor phenotype, which leaves critical gap comprehending the ACh transmission manifestation dystonia. To tackle this question, we used combination ex vivo slice physiology monitoring dynamics inducible, phenotypically penetrant, transgenic model paroxysmal non-kinesigenic dyskinesia (PNKD). We found that, similarly other models, PNKD displays D2R-induced ChI firing brain slices. In , caffeine triggers symptoms while reversing D2R-mediated ChIs desynchronizing network. WT littermate controls, stimulates spontaneous locomotion through similar but reversed mechanism involving an excitatory switch D2R control activity, associated enhanced network synchronization. Together these observations suggest that D2Rs may important synchronizing during heightened movement states. The “paradoxical excitation” described could represent compensatory or protective prevents abnormalities allows for phenotypic when lost.
Язык: Английский
Процитировано
0
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(16), С. 8610 - 8610
Опубликована: Авг. 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.
Язык: Английский
Процитировано
0
Exploration of Neuroprotective Therapy, Год журнала: 2024, Номер 4(5), С. 366 - 391
Опубликована: Сен. 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.
Язык: Английский
Процитировано
0
Frontiers in Aging Neuroscience, Год журнала: 2024, Номер 16
Опубликована: Сен. 26, 2024
Delirium is an acute, global cognitive disorder syndrome, also known as acute brain characterized by disturbance of attention and awareness fluctuation symptoms. Its incidence high among critically ill patients. Once patients develop delirium, it increases the risk unplanned extubation, prolongs hospital stay, nosocomial infection, post-intensive care syndrome-cognitive impairment, even death. Therefore, great importance to understand how delirium occurs reduce in This paper reviews potential pathophysiological mechanisms patients, with aim better understanding its processes, guiding formulation effective prevention treatment strategies, providing a basis for clinical medication.
Язык: Английский
Процитировано
0
Neurobiology of Disease, Год журнала: 2024, Номер unknown, С. 106685 - 106685
Опубликована: Сен. 1, 2024
Язык: Английский
Процитировано
0
Engineering, Год журнала: 2024, Номер 44, С. 256 - 265
Опубликована: Дек. 25, 2024
Язык: Английский
Процитировано
0