Acute isoproterenol induces anxiety-like behavior in rats and increases plasma content of extracellular vesicles

Leo, Giuseppina; Guescini, Michele; Genedani, Susanna; Stocchi, Vilberto; Carone, Chiara; Filaferro, Monica; Sisti, Davide; Marcoli, Manuela; Maura, Guido; Cortelli, Pietro; Guidolin, Diego; Fuxé, Kjell; Agnati, Luigi F.

doi:10.1016/j.physbeh.2015.02.002

“…Moreover, recent evidence demonstrated that EVs may transfer to target cells genetic information, in particular, microRNA (miRNA) [ 15 , 16 , 20 , 25 , 26 , 27 ] and DNA [ 17 , 28 , 29 ]. miRNA are a class of 20–22 nucleotide non-coding RNAs that regulate gene expression in mammals at the post-transcriptional level [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles Released by Oxidatively Injured or Intact C2C12 Myotubes Promote Distinct Responses Converging toward Myogenesis

Guescini

¹

,

Maggio

²

,

Ceccaroli

³

et al. 2017

IJMS

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Myogenic differentiation is triggered, among other situations, in response to muscle damage for regenerative purposes. It has been shown that during myogenic differentiation, myotubes release extracellular vesicles (EVs) which participate in the signalling pattern of the microenvironment. Here we investigated whether EVs released by myotubes exposed or not to mild oxidative stress modulate the behaviour of targeted differentiating myoblasts and macrophages to promote myogenesis. We found that EVs released by oxidatively challenged myotubes (H2O2-EVs) are characterized by an increased loading of nucleic acids, mainly DNA. In addition, incubation of myoblasts with H2O2-EVs resulted in a significant decrease of myotube diameter, myogenin mRNA levels and myosin heavy chain expression along with an upregulation of proliferating cell nuclear antigen: these effects collectively lead to an increase of recipient myoblast proliferation. Notably, the EVs from untreated myotubes induced an opposite trend in myoblasts, that is, a slight pro-differentiation effect. Finally, H2O2-EVs were capable of eliciting an increased interleukin 6 mRNA expression in RAW264.7 macrophages. Notably, this is the first demonstration that myotubes communicate with surrounding macrophages via EV release. Collectively, the data reported herein suggest that myotubes, depending on their conditions, release EVs carrying differential signals which could contribute to finely and coherently orchestrate the muscle regeneration process.

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“…At a similar dose, ISO has been shown to mediate anti-depressant effects (Zhang et al ., 2001); however, it is not likely this would explain the increases in latency. Similarly, these effects were not the result of changes in anxiety-related behavior given all animals spent more time in the open arms of the EPM, suggesting both ISO and PRO do not impart anxiogenic effects, an important determination since altered BAR function and heightened noradrenergic tone have been linked to anxiety in the past (Leo et al ., 2015). In contrast, PRO is associated with attenuated physiological responses to anxiety (Nandhra et al ., 2013; Argolo et al ., 2015).…”

Section: Discussionmentioning

confidence: 97%

Norepinephrine as a spatial memory reset signal

Grella

¹

,

Gomes

²

,

Lackie

³

et al. 2021

Behavioural Pharmacology

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Contextual information is represented in the hippocampus (HPC) partially through the recruitment of distinct neuronal ensembles. It is believed that reactivation of these ensembles underlies memory retrieval processes. Recently, we showed that norepinephrine input from phasic locus coeruleus activation induces hippocampal plasticity resulting in the recruitment of new neurons and disengagement from previously established representations. We hypothesize that norepinephrine may provide a neuromodulatory mnemonic switch signaling the HPC to move from a state of retrieval to encoding in the presence of novelty, and therefore, plays a role in memory updating. Here, we tested whether bilateral dorsal dentate gyrus (dDG) infusions of the β-adrenergic receptor (BAR) agonist isoproterenol (ISO), administered prior to encoding or retrieval, would impair spatial working and reference memory by reverting, the system to encoding (thereby recruiting new neurons) potentially interfering with the retrieval of the previously established spatial ensemble. We also investigated whether dDG infusions of ISO could promote cognitive flexibility by switching the system to encoding when it is adaptive (ie, when new information is presented, eg, reversal learning). We found that intra-dDG infusions of ISO given prior to retrieval caused deficits in working and reference memory which was blocked by pretreatment with the BAR-antagonist, propranolol (PRO). In contrast, ISO administered prior to reversal learning led to improved performance. These data support our hypothesis that norepinephrine serves as a novelty signal to update HPC contextual representations via BAR activation-facilitated recruitment of new neurons. This can be both maladaptive and adaptive depending on the situation. Behavioural

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“…At a similar dose, ISO has been shown to mediate anti-depressant effects (Zhang, Frith, and Wilkins, 2001), however, it is not likely this would explain the increases in latency. Similarly, these effects were not the result of changes in anxiety-related behavior given all animals spent more time in the open arms of the EPM, suggesting both ISO and PRO do not impart anxiogenic effects, an important determination since altered BAR function and heightened noradrenergic tone have been linked to anxiety in the past (Leo, Guescini, Genedani, Stocchi, Carone, Filaferro et al, 2015). In contrast, PRO is associated with attenuated physiological responses to anxiety (Nandhra, Murphy and Sule, 2013;Argolo, Cavalcanti-Ribeiro, and Netto, 2015).…”

Section: Discussionmentioning

confidence: 97%

Norepinephrine as a Spatial Memory Reset Signal

Grella

¹

,

Gomes

²

,

Lackie

³

et al. 2020

Preprint

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Contextual information is represented in the hippocampus (HPC) partially through the recruitment of distinct neuronal ensembles. It is believed that reactivation of these ensembles underlies memory retrieval processes. Recently, we showed that norepinephrine (NE) input from phasic locus coeruleus (LC) activation induces hippocampal plasticity resulting in the recruitment of new neurons and a disengagement from previously established representations. We hypothesize that NE may provide a neuromodulatory, mnemonic switch signaling the HPC to move from a state of retrieval to encoding in the presence of novelty, and therefore, plays a role in memory updating.Here, we tested whether bilateral dorsal dentate gyrus (DG) infusions of the βadrenergic receptor (BAR) agonist isoproterenol (ISO), administered prior to encoding or retrieval, would impair spatial working and reference memory by reverting the system to encoding (thereby recruiting new neurons) potentially interfering with retrieval of the previously established spatial ensemble. We also investigated whether dDG infusions of ISO could promote cognitive flexibility by switching the system to encoding when it is adaptive (i.e. when new information is presented e.g. reversal learning). We found that intra-dDG infusions of ISO given prior to retrieval caused deficits in working and reference memory which was blocked by pre-treatment with the BAR-antagonist, propranolol (PRO). In contrast, ISO administered prior to reversal learning led to improved performance. These data support our hypothesis that NE serves as a novelty signal to update HPC contextual representations via BAR activation-facilitated recruitment of new neurons. This can be both maladaptive and adaptive depending on the situation. Grella et al., 3an inability to remap hippocampal contextual representations (i.e., trauma-related representations are reactivated rather than incorporating safety signals into existing memory traces) (Maren et al., 2013; Morrison and Ressler, 2014; Giustino et al., 2016; Liberzon and Abelson, 2016; Elsey and Kindt, 2017; Lee et al., 2017; Sheynin and Liberzon, 2017). The pathophysiology of anxiety disorders such as PTSD is characterized by noradrenergic dysregulation (Hendrickson and Raskind, 2016). We believe the locus coeruleus (LC), the site of noradrenergic cell bodies, plays a role in Grella et al., 5 memory updating, specifically by biasing the system towards encoding. This suggests that individuals with PTSD may be experiencing an inability to engage this transition to encoding through dysfunction of the LC norepinephrine (NE) system.The LC responds to salience cues including novelty and sends a major noradrenergic projection to the dentate gyrus (DG) (Aston-Jones and Bloom, 1981;Vankov et al.

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Acute isoproterenol induces anxiety-like behavior in rats and increases plasma content of extracellular vesicles

Cited by 9 publications

References 46 publications

Extracellular Vesicles Released by Oxidatively Injured or Intact C2C12 Myotubes Promote Distinct Responses Converging toward Myogenesis

Extracellular Vesicles Released by Oxidatively Injured or Intact C2C12 Myotubes Promote Distinct Responses Converging toward Myogenesis

Norepinephrine as a spatial memory reset signal

Norepinephrine as a Spatial Memory Reset Signal

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