Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 177, С. 117042 - 117042
Опубликована: Июль 14, 2024
Язык: Английский
Molecular Psychiatry, Год журнала: 2024, Номер 29(5), С. 1265 - 1280
Опубликована: Янв. 16, 2024
Abstract Early and progressive dysfunctions of the dopaminergic system from Ventral Tegmental Area (VTA) have been described in Alzheimer’s Disease (AD). During long pre-symptomatic phase, alterations function Parvalbumin interneurons (PV-INs) are also observed, resulting cortical hyperexcitability represented by subclinical epilepsy aberrant gamma-oscillations. However, it is unknown whether deficits contribute to brain AD. Here, using Tg2576 mouse model AD, we prove that reduced hippocampal innervation, due VTA dopamine neuron degeneration, impairs PV-IN firing gamma-waves, weakens inhibition pyramidal neurons induces via lower D2-receptor-mediated activation CREB-pathway. These coincide with numbers Perineuronal Net density. Importantly, L-DOPA selective D2-receptor agonist quinpirole rescue p -CREB levels improve PV-IN-mediated inhibition, thus reducing hyperexcitability. Moreover, similarly quinpirole, sumanirole – another a known anticonvulsant not only increases PV-INs but restores gamma-oscillations mice. Conversely, blocking transmission sulpiride (a D2-like receptor antagonist) WT mice reduces PV-INs, mimicking what occurs Tg2576. Overall, these findings support hypothesis integrity plays key role survival, disclosing relevant contribution tone epileptiform activity early
Язык: Английский
Процитировано
21
ECS Sensors Plus, Год журнала: 2024, Номер 3(2), С. 020601 - 020601
Опубликована: Апрель 1, 2024
Dopamine is an essential neurotransmitter for daily cognitive functions controlling many neurophysiological processes including memory, cognition, and physical control. Development of analytical methods sensors to detect dopamine important health monitoring neurological research. This review provides overview recent advances in the development electrochemical catalytic biosensors based on enzyme enzyme-mimetic materials discusses their potential applications measurements biological fluids. The first part summarizes critically assesses different types enzymes mimetic that can be used catalytically convert dopamine, followed by a discussion biosensor’s fabrication, key design parameters, detection mechanism various electrode platforms ranging from single-use screen-printed electrodes microneedles implantable microelectrodes. second examples samples, saliva, urine, serum, cell cultures, brain tissue. We conclude with summary advantages limitations these devices clinical field, outlook future research towards implementation broader adoption neurophysiology, pharmacology, field.
Язык: Английский
Процитировано
20
International Journal of Biological Sciences, Год журнала: 2024, Номер 20(5), С. 1927 - 1946
Опубликована: Янв. 1, 2024
The activation of NLRP3 inflammasome in microglia is critical for neuroinflammation during postoperative cognitive dysfunction (POCD) induced by sevoflurane.However, the molecular mechanism which sevoflurane activates remains unclear.The cGAS-STING pathway an evolutionarily conserved inflammatory defense mechanism.The role sevoflurane-induced inflammasome-dependent and underlying mechanisms require further investigation.We found that prolonged anesthesia with triggered characterized vivo.Interestingly, was activated hippocampus mice receiving sevoflurane.While blockade cGAS RU.521 attenuated mice.In vitro, we treatment significantly microglia, while pre-treatment robustly inhibited activation.Mechanistically, mitochondrial fission released DNA (mtDNA) into cytoplasm, could be abolished Mdivi-1.Blocking mtDNA release via mPTP-VDAC channel inhibitor cytosolic escape reduced finally inhibiting activation.Therefore, regulating targeting may provide a novel therapeutic target POCD.
Язык: Английский
Процитировано
19
Neurobiology of Disease, Год журнала: 2023, Номер 185, С. 106253 - 106253
Опубликована: Авг. 2, 2023
N6-methyladenosine (m6A) plays a crucial role in ischemic stroke, whereas the of methyltransferase-like 14 (METTL14) stroke remains unknown. A model middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation/reperfusion (OGD/R) HAPI cells were used to simulate vivo vitro. We found that METTL14 level was upregulated microglia/macrophage after MCAO OGD/R. enhanced expression KAT3B by promoting m6A modification mRNA. STING has been identified as target for increased enhancing H3K27ac promoter. promoted M1 polarization NLRP3 inflammasome/pyroptosis axis KAT3B-STING signaling depletion relieved brain injury inhibiting M1-like rats. These findings indicate relieves MCAO-induced injury, probably via switching from towards M2 restraining microglia/macrophage.
Язык: Английский
Процитировано
33
iScience, Год журнала: 2024, Номер 27(4), С. 109568 - 109568
Опубликована: Март 26, 2024
Highlights•This study analyzed pathways of differentially expressed mRNAs in people with RLS•Nine closely interconnected network groups emerged to be significantly dysregulated•Among them: infections, inflammation, immunology, neurodegeneration, and cancer•Infections could trigger inflammatory/immune reactions predisposed subjectsSummaryThe aim this was analyze signaling associated messenger RNAs restless legs syndrome (RLS). Seventeen RLS patients 18 controls were enrolled. Coding RNA expression profiling 12,857 gene transcripts by next-generation sequencing performed. Enrichment analysis pathfindR tool carried-out, p-adjusted ≤0.001 fold-change ≥2.5. Nine main different dysregulated RLS: cancer, neurotransmission biological, blood metabolic mechanisms. Genetic predisposition plays a key role evidence indicates its inflammatory nature; the high involvement mainly neurotropic viruses TORCH complex might genetically subjects activate series biological pathways—especially IL-17, receptor potential channels, nuclear factor kappa-light-chain-enhancer activated B cells, NOD-like receptor, mitogen-activated protein kinase, p53, mitophagy, ferroptosis—involved neurotransmitter mechanisms, synaptic plasticity, axon guidance, carcinogenesis, metabolism.Graphical abstract
Язык: Английский
Процитировано
10
Molecular Neurobiology, Год журнала: 2025, Номер unknown
Опубликована: Фев. 25, 2025
Язык: Английский
Процитировано
1
Neuropharmacology, Год журнала: 2023, Номер 237, С. 109636 - 109636
Опубликована: Июнь 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.
Язык: Английский
Процитировано
17
Progress in Neurobiology, Год журнала: 2024, Номер 234, С. 102574 - 102574
Опубликована: Янв. 22, 2024
Язык: Английский
Процитировано
6
Phytomedicine, Год журнала: 2024, Номер 126, С. 155435 - 155435
Опубликована: Фев. 13, 2024
Язык: Английский
Процитировано
6
Brain Communications, Год журнала: 2024, Номер 6(4)
Опубликована: Янв. 1, 2024
Parkinson's disease is a progressive neurodegenerative disorder characterized by the deposition of misfolded alpha-synuclein in different regions central and peripheral nervous system. Motor impairment represents signature clinical expression disease. Nevertheless, non-motor symptoms are invariably present at stages constitute an important therapeutic challenge with high impact for patients' quality life. Among symptoms, pain frequently experienced patients, being range 24-85% population. Moreover, more than 5% first manifestation, preceding decades exordium motor symptoms. Pain implies complex biopsychosocial experience downstream anatomical network involved perception, modulation, processing. Interestingly, all areas can be affected a-synuclein pathology, suggesting that pathophysiology encompasses 'pain spectrum', involving neurochemical substrates. Here various sites recruited modulation processing discussed, highlighting consequences their possible degeneration course Starting from small fibres neuropathy pathological alterations level posterior laminae spinal cord, we then describe multifaceted role noradrenaline dopamine loss driving dysregulated perception. Finally, focus on intertwined circuits between amygdala, nucleus accumbens habenula determining psycho-emotional, autonomic cognitive This narrative review provides anatomically driven comprehension disease, aiming fostering new insights personalized diagnosis interventions.
Язык: Английский
Процитировано
6