Acute Functional Adaptations in Isolated Presynaptic Terminals Unveil Synaptosomal Learning and Memory

Pittaluga, Anna

doi:10.3390/ijms20153641

Cited by 15 publications

(21 citation statements)

References 72 publications

(115 reference statements)

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“…Learning and memory impairments as well as mood disorders and anxiety mainly rely on alteration of the chemical neurotransmission in selected regions of the central nervous system (CNS), particularly affecting the catecholaminergic, the cholinergic and the GABAergic pathways. These systems are selected targets of aging processes, as the efficiency of the synthesis and the release of these neuromodulators, as well as the expression of the corresponding membrane receptors, result in impairments in old brains [1][2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammation in Aged Brain: Impact of the Oral Administration of Ellagic Acid Microdispersion

Boggia

Turrini

Roggeri

et al. 2020

IJMS

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The immune system and the central nervous system message each other to preserving central homeostasis. Both systems undergo changes during aging that determine central age-related defects. Ellagic acid (EA) is a natural product which is beneficial in both peripheral and central diseases, including aging. We analyzed the impact of the oral administration of a new oral ellagic acid micro-dispersion (EAm), that largely increased the EA solubility, in young and old mice. Oral EAm did not modify animal weight and behavioral skills in young and old mice, but significantly recovered changes in “ex-vivo, in vitro” parameters in old animals. Cortical noradrenaline exocytosis decreased in aged mice. EAm administration did not modify noradrenaline overflow in young animals, but recovered it in old mice. Furthermore, GFAP staining was increased in the cortex of aged mice, while IBA-1 and CD45 immunopositivities were unchanged when compared to young ones. EAm treatment significantly reduced CD45 signal in both young and old cortical lysates; it diminished GFAP immunopositivity in young mice, but failed to affect IBA-1 expression in both young and old animals. Finally, EAm treatment significantly reduced IL1beta expression in old mice. These results suggest that EAm is beneficial to aging and represents a nutraceutical ingredient for elders.

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Section: Introductionmentioning

confidence: 99%

Neuroinflammation in Aged Brain: Impact of the Oral Administration of Ellagic Acid Microdispersion

Boggia

Turrini

Roggeri

et al. 2020

IJMS

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“…Owing to address this question, we focussed on synaptosomes, which are re-sealed pinched off nerve terminals that retain the functional properties of the presynaptic component they originate from (Pittaluga et al, 2019) and that we propose as an appropriate model to highlight the presence and the release of exosomes from nerve terminals.…”

Section: Discussionmentioning

confidence: 99%

“…Synaptosomes represent the simplest model to study the Ca 2+ -dependent exocytosis of transmitters from synaptic vesicles (Raiteri and Raiteri, 2000;Pittaluga, 2019). The finding that the enrichment of exosomal markers in the exosomal fraction isolated from the supernatants of depolarized synaptosomes was almost undetectable when nerve terminals were stimulated with the 25 mM KCl medium lacking Ca 2+ ions suggests that the release of exosomes is a Ca 2+ -dependent event, as already described in the literature (Savina et al, 2003;Krämer-Albers et al, 2007;Lachenal et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…The transmitter exocytosis is presynaptically controlled by auto-and heteroreceptors (Raiteri, 2001;Langer, 2008;Pittaluga, 2019). Interestingly, the depolarization-evoked Ca 2+ -dependent secretion of exosomes from cultured cortical neurons was shown to be controlled by GABA A ligands, allowing the conclusion that the release of exosomes from these cells can be mediated by synaptic receptors activity (Lachenal et a., 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Glutamate exocytosis from cortical synaptosomes is an active process controlled by auto-and heteroreceptors presynaptically located in nerve terminals. In particular, presynaptic GABA B heteroreceptors exist in cortical glutamatergic nerve endings: they are inhibitory G-coupled receptors, whose activation reduces the adenylyl cyclase activity and the Ca 2+ conductance, inhibiting glutamate exocytosis from the nerve endings (Bonanno and Raiteri., 1993;Grilli et al, 2004;Pittaluga 2019). Accordingly, the glutamate content in the supernatants of synaptosomes exposed to 25 mM KCl medium in the presence of the GABA B receptor agonist (±)-baclofen (10 μM) was significantly lower than that in the supernatants of synaptosomes exposed to the depolarizing stimulus alone ( Figure 6A).…”

Section: Comparative Analysis Of Exosomal and Synaptosomal Markers Inmentioning

confidence: 95%

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The depolarization-evoked, Ca2+-dependent release of exosomes from mouse cortical nerve endings: new insights into synaptic transmission.

Olivero

Cisani

Marimpietri

et al. 2020

Preprint

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Background and purpose Exosomes, nanosized extracellular vesicles, emerged as players in the cell-to-cell communication in the central nervous system (CNS), having a role in the modulation of the synaptic activity. This study aimed at evaluating whether exosomes can be actively released from presynaptic nerve terminals. Experimental Approach Mouse cortical synaptosomes were exposed to a depolarizing stimulus (25 mM KCl medium) and exosomes were isolated from the synaptosomal supernatants. Exosomes were characterized by dynamic light scattering, transmission electron microscopy, western blot and flow cytometry analyses. We also evaluated whether and how removing external Ca2+ ions or activating presynaptic GABAB receptors by exposing synaptosomes to (±)-baclofen (10 μM) affects the 25 mM KCl-evoked release of exosomes. Key Results The structural and biochemical analysis unveiled that synaptosomal supernatants contained vesicles having the size and the shape of exosomes, immunopositive for the exosomal markers TSG101, flotillin-1, CD63 and CD9. The content of these proteins in the exosomal fraction isolated from synaptosomal supernatants increased upon the exposure of nerve terminals to a depolarizing stimulus and occurred in a Ca2+-dependent fashion, mimicking the release of glutamate. (±)-Baclofen significantly reduced glutamate exocytosis but failed to affect the release of exosomes from cortical synaptosomes. Finally, presynaptic exosomes were shown to carry selected NMDA and AMPA receptors subunits. Conclusion and implications Our study unveils the Ca2+-dependent, depolarization-evoked release of exosomes from mouse cortical nerve terminals, which is insensitive to presynaptic releaseregulating GABAB receptors. These findings add new insights into the mechanisms of exosomes-mediated communication in CNS. Background and purpose Exosomes, nanosized extracellular vesicles, emerged as players in the cell-to-cell communication in the central nervous system (CNS), having a role in the modulation of the synaptic activity. This study aimed at evaluating whether exosomes can be actively released from presynaptic nerve terminals. Experimental Approach Mouse cortical synaptosomes were exposed to a depolarizing stimulus (25 mM KCl medium) and exosomes were isolated from the synaptosomal supernatants. Exosomes were characterized by dynamic light scattering, transmission electron microscopy, western blot and flow cytometry analyses. We also evaluated whether and how removing external Ca 2+ ions or activating presynaptic GABA B receptors by exposing synaptosomes to (±)-baclofen (10 μM) affects the 25 mM KCl-evoked release of exosomes.

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Synaptosomes and Metamodulation of Receptors

Pittaluga

Marchi

2022

Methods in Molecular Biology

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Acute Functional Adaptations in Isolated Presynaptic Terminals Unveil Synaptosomal Learning and Memory

Cited by 15 publications

References 72 publications

Neuroinflammation in Aged Brain: Impact of the Oral Administration of Ellagic Acid Microdispersion

Neuroinflammation in Aged Brain: Impact of the Oral Administration of Ellagic Acid Microdispersion

The depolarization-evoked, Ca2+-dependent release of exosomes from mouse cortical nerve endings: new insights into synaptic transmission.

Synaptosomes and Metamodulation of Receptors

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