Based on the model of the adrenergic neurone proposed earlier, the dynamics of nerve-pulse transmission after treatment with inhibitors of neuronal uptake and catechol-O-methyltransferase, alpha 1-adrenoceptor antagonists, changes in the concentration of Ca2+ ions in the external medium, the action of tetrodotoxin (TTX) and repetitive stimulation, are analysed. The results of numerical simulation show that: the addition of drugs that inhibit neuronal uptake and catechol-O-methyltransferase cause the augmentation of noradrenaline action on post-synaptic structures and an increase in the amplitude of the generated inhibitory post-synaptic potential (IPSP); treatment with adrenergic antagonists reduces the amplitude of IPSP; decrease in the concentration of extracellular Ca2+ ions and application of TTX abolish the post-synaptic response. All these effects are shown to be dose-dependent. The repetitive stimulation of the neurone reproduces the effects of accumulation and potentiation. Possible applications of the results obtained are discussed.
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http://dx.doi.org/10.1016/1350-4533(95)01003-b | DOI Listing |
Hum Brain Mapp
February 2025
Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Groningen, The Netherlands.
Cognitive impairment is considered to be one of the key features of Parkinson's disease (PD), ultimately resulting in PD-related dementia in approximately 80% of patients over the course of the disease. Several distinct cognitive syndromes of PD have been suggested, driven by different neurotransmitter deficiencies and thus requiring different treatment regimes. In this study, we aimed to identify characteristic brain covariance patterns that reveal how cholinergic denervation is related to PD and to cognitive impairment, focusing on four domains, including attention, executive functioning, memory, and visuospatial cognition.
View Article and Find Full Text PDFSci Transl Med
January 2025
Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, 81377 Munich, Germany.
In Alzheimer's disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration and cognitive decline. However, the pathophysiological link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ-related tau accumulation. Aβ has been found to trigger neuronal hyperactivity and hyperconnectivity, and preclinical research has shown that tau spreads across connected neurons in an activity-dependent manner.
View Article and Find Full Text PDFAdv Compos Hybrid Mater
January 2025
J. Mike Walker '66 Department of Mechanical Engineering, Texas A&M University, College Station, TX 77843 USA.
Dosage tolerance is one of the translational challenges of using metformin (Met) in brain therapeutics. This paper presents metal-organic framework (MOF)-74-Mg nanocarriers (NCs) for intranasal (IN) delivery of brain-specific agents with a prolonged release time. We confirmed their excellent biocompatibility (5 mg/mL) and intrinsic fluorescence properties (370/500 nm excitation/emission peak) in Neuro-2A cells.
View Article and Find Full Text PDFAlzheimer's disease (AD) is an age-related neurodegenerative pathology. Brain-derived extracellular vesicles (EVs) have been demonstrated to be implicated in AD pathogenesis by facilitating the propagation of Tau, amyloid-β and inflammatory cytokines. However, the impact of peripheral EVs (pEVs) in AD pathogenesis remains poorly investigated.
View Article and Find Full Text PDFMitochondrial ATP production and calcium buffering are critical for metabolic regulation and neurotransmission making the formation and maintenance of the mitochondrial network a critical component of neuronal health. Cortical pyramidal neurons contain compartment-specific mitochondrial morphologies that result from distinct axonal and dendritic mitochondrial fission and fusion profiles. We previously showed that axonal mitochondria are maintained at a small size as a result of high axonal mitochondrial fission factor (Mff) activity.
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