Cytoplasmic Ca2+ concentration changes evoked by cholinergic stimulation in primary astrocyte cultures prepared from the rat cochlear nucleus

Pap, Pál; Kőszeghy, Áron; Szücs, G; Rusznák, Zoltán

doi:10.1016/j.heares.2009.05.006

Cited by 21 publications

(15 citation statements)

References 52 publications

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“…An example is presented in Figs 5f1-f3, where the cell indicated by ' ' showed markedly different nuclear morphology (narrow, elongated nucleus as opposed to the more spherical ones characteristic of the granule cells) and did not present M3-specific immunopositivity. Although the precise identity of this and similar cells was not sought in the present work, they may have corresponded to representatives of a subclass of astrocytes that do not express M3 receptors [27]. Nevertheless, the existence of M3 receptor negative cells was an important observation, as it indicated that the immunohistochemistry results were not the consequences of non-specific labelling.…”

Section: The Role Of M1 and M3 Receptors In The Cch Effectsmentioning

confidence: 73%

Activation of muscarinic receptors increases the activity of the granule neurones of the rat dorsal cochlear nucleus—a calcium imaging study

Kőszeghy

Vincze

Rusznák

et al. 2012

Pflugers Arch - Eur J Physiol

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Acetylcholine modulates the function of the cochlear nucleus via several pathways. In this study the effects of cholinergic stimulation were studied on the cytoplasmic Ca 2+ concentration of granule neurones of the rat dorsal cochlear nucleus (DCN). Ca 2+ transients were recorded in Oregon-Green-BAPTA 1-loaded brain slices using a calcium imaging technique. For the detection, identification, and characterisation of the Ca 2+ transients, a wavelet analysis-based method was developed. Granule cells were identified on the basis of their size and localisation. The action potential-coupled character of the Ca 2+ transients of the granule cells was established by recording fluorescence changes and electrical activity simultaneously. Application of the cholinergic agonist carbamyl-choline (CCh) significantly increased the frequency of the Ca 2+ transients (from 0.37 to 6.31 min -1 , corresponding to a 17.1-fold increase; n = 89).This effect was antagonised by atropine, whereas CCh could still evoke an 8.3-fold increase of the frequency of the Ca 2+ transients when hexamethonium was present.Using immunolabelling, the expression of both type 1 and type 3 muscarinic receptors (M1 and M3 receptors, respectively) was demonstrated in the granule cells. Application of 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (an M3-specific antagonist) prevented the onset of the CCh effect, whereas an M1-specific antagonist (pirenzepine) was less effective. We conclude that cholinergic stimulation increases the activity of granule cells, mainly by acting on their M3 receptors. The modulation of the firing activity of the granule cells, in turn, may modify the firing of projection neurones, and may adjust signal processing in the entire DCN.

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Section: The Role Of M1 and M3 Receptors In The Cch Effectsmentioning

confidence: 73%

Activation of muscarinic receptors increases the activity of the granule neurones of the rat dorsal cochlear nucleus—a calcium imaging study

Kőszeghy

Vincze

Rusznák

et al. 2012

Pflugers Arch - Eur J Physiol

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“…Intracellular calcium (Ca 2+ ) concentration changes evoked by cholinergic stimulation were assessed according to refs. [40,41] with minor modifications. For the measurement, the fluorescent dye Fluo-3 (Fluo-3 AM; Thermo Fisher Scientific, cat: F1242) was employed.…”

Section: Evaluation Of Intracellular Hydrogen Peroxide (H 2 O 2 ) By mentioning

confidence: 99%

Cholinergic-like neurons carrying PSEN1 E280A mutation from familial Alzheimer’s disease reveal intraneuronal sAPPβ fragments accumulation, hyperphosphorylation of TAU, oxidative stress, apoptosis and Ca2+ dysregulation: Therapeutic implications

et al. 2020

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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and cognitive disturbance as a consequence of the loss of cholinergic neurons in the brain, neuritic plaques and hyperphosphorylation of TAU protein. Although the underlying mechanisms leading to these events are unclear, mutations in presenilin 1 (PSEN1), e.g., E280A (PSEN1 E280A), are causative factors for autosomal dominant early-onset familial AD (FAD). Despite advances in the understanding of the physiopathology of AD, there are no efficient therapies to date. Limitations in culturing brain-derived live neurons might explain the limited effectiveness of AD research. Here, we show that mesenchymal stromal (stem) cells (MSCs) can be used to model FAD, providing novel opportunities to study cellular mechanisms and to establish therapeutic strategies. Indeed, we cultured MSCs with the FAD mutation PSEN1 E280A and wild-type (WT) PSEN1 from umbilical cords and characterized the transdifferentiation of these cells into cholinergic-like neurons (ChLNs). PSEN1 E280A ChLNs but not WT PSEN1 ChLNs exhibited increased intracellular soluble amyloid precursor protein (sAPPf) fragments and extracellular Aβ42 peptide and TAU phosphorylation (at residues Ser202/Thr205), recapitulating the molecular pathogenesis of FAD caused by mutant PSEN1. Furthermore, PSEN1 E280A ChLNs presented oxidative stress (OS) as evidenced by the oxidation of DJ-1Cys 106-SH into DJ-1Cys 106-SO 3 and the detection of DCF-positive cells and apoptosis markers such as activated pro-apoptosis proteins p53, c-JUN, PUMA and CASPASE-3 and the concomitant loss of the mitochondrial membrane potential and DNA fragmentation. Additionally, mutant ChLNs displayed Ca 2+ flux dysregulation and deficient acetylcholinesterase (AChE) activity compared to control ChLNs. Interestingly, the inhibitor JNK SP600125 almost completely blocked TAU phosphorylation. Our findings demonstrate that FAD MSC-derived cholinergic neurons with the

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“…Glial cells, mainly astrocytes, express a diversity of mAChRs including M1 and M3 (Pap et al, 2009). In several brain regions activation of mAChRs on glia cause elevations in intracellular glial [Ca 2+ ] i (Araque et al, 2002; Pap et al, 2009; Takata et al, 2011; Navarrete et al, 2012). Glia participate in the induction of synaptic plasticity in the hippocampus, including a form of LTP at the CA3-CA1 synapses that is dependent on activation of mAChRs (Navarrete et al, 2012).…”

Section: Machr Driven Ecb Release and Electrical Synaptic Connectionsmentioning

confidence: 99%

Muscarinic cholinergic receptors modulate inhibitory synaptic rhythms in hippocampus and neocortex

Alger

Nagode

Tang

2014

Front. Synaptic Neurosci.

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Activation of muscarinic acetylcholine (ACh) receptors (mAChRs) powerfully affects many neuronal properties as well as numerous cognitive behaviors. Small neuronal circuits constitute an intermediate level of organization between neurons and behaviors, and mAChRs affect interactions among cells that compose these circuits. Circuit activity is often assessed by extracellular recordings of the local field potentials (LFPs), which are analogous to in vivo EEGs, generated by coordinated neuronal interactions. Coherent forms of physiologically relevant circuit activity manifest themselves as rhythmic oscillations in the LFPs. Frequencies of rhythmic oscillations that are most closely associated with animal behavior are in the range of 4–80 Hz, which is subdivided into theta (4–14 Hz), beta (15–29 Hz) and gamma (30–80 Hz) bands. Activation of mAChRs triggers rhythmic oscillations in these bands in the hippocampus and neocortex. Inhibitory responses mediated by GABAergic interneurons constitute a prominent feature of these oscillations, and indeed, appear to be their major underlying factor in many cases. An important issue is which interneurons are involved in rhythm generation. Besides affecting cellular and network properties directly, mAChRs can cause the mobilization of endogenous cannabinoids (endocannabinoids, eCBs) that, by acting on the principal cannabinoid receptor of the brain, CB1R, regulate the release of certain neurotransmitters, including GABA. CB1Rs are heavily expressed on only a subset of interneurons and, at lower density, on glutamatergic neurons. Exogenous cannabinoids typically disrupt oscillations in the theta (θ) and gamma (γ) ranges, which probably contributes to the behavioral effects of these drugs. It is important to understand how neuronal circuit activity is affected by mAChR-driven eCBs, as this information will provide deeper insight into the actions of ACh itself, as well as into the effects of eCBs and exogenous cannabinoids in animal behavior. After covering some basic aspects of the mAChR system, this review will focus on recent findings concerning the mechanisms and circuitry that generate θ and γ rhythms in hippocampus and neocortex. The ability of optogenetic methods to probe the many roles of ACh in rhythm generation is highlighted.

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Cytoplasmic Ca2+ concentration changes evoked by cholinergic stimulation in primary astrocyte cultures prepared from the rat cochlear nucleus

Cited by 21 publications

References 52 publications

Activation of muscarinic receptors increases the activity of the granule neurones of the rat dorsal cochlear nucleus—a calcium imaging study

Activation of muscarinic receptors increases the activity of the granule neurones of the rat dorsal cochlear nucleus—a calcium imaging study

Cholinergic-like neurons carrying PSEN1 E280A mutation from familial Alzheimer’s disease reveal intraneuronal sAPPβ fragments accumulation, hyperphosphorylation of TAU, oxidative stress, apoptosis and Ca2+ dysregulation: Therapeutic implications

Muscarinic cholinergic receptors modulate inhibitory synaptic rhythms in hippocampus and neocortex

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