Dataset Information

The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between Apoptosis and Autophagy.

ABSTRACT: In a mouse model of oxygen induced retinopathy (OIR), beta adrenergic receptor (BAR) blockade has been shown to recover hypoxia-associated retinal damages. Although the adrenergic signaling is an important regulator of apoptotic and autophagic processes, the role of BARs in retinal cell death remains to be elucidated. The present study was aimed at investigating whether ameliorative effects of BAR blockers may occur through their coordinated action on apoptosis and autophagy. To this aim, retinas from control and OIR mice untreated or treated with propranolol, a non-selective BAR1/2 blocker, were characterized in terms of expression and localization of apoptosis and autophagy markers. The effects of propranolol on autophagy signaling were also evaluated and specific autophagy modulators were used to get functional information on the autophagic effects of BAR antagonism. Finally, propranolol effects on neurodegenerative processes were associated to an electrophysiological investigation of retinal function by recording electroretinogram (ERG). We found that retinas of OIR mice are characterized by increased apoptosis and decreased autophagy, while propranolol reduces apoptosis and stimulates autophagy. In particular, propranolol triggers autophagosome formation in bipolar, amacrine and ganglion cells that are committed to die by apoptosis in response to hypoxia. Also our data argue that propranolol, through the inhibition of the Akt-mammalian target of rapamycin pathway, activates autophagy which decreases retinal cell death. At the functional level, propranolol recovers dysfunctional ERG by recovering the amplitude of a- and b-waves, and oscillatory potentials, thus indicating an efficient restoring of retinal transduction. Overall, our results demonstrate that BAR1/2 are key regulators of retinal apoptosis/autophagy, and that BAR1/2 blockade leads to autophagy-mediated neuroprotection. Reinstating the balance between apoptotic and autophagic machines may therefore be viewed as a future goal in the treatment of retinopathies.

SUBMITTER: Cammalleri M

PROVIDER: S-EPMC5770647 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between Apoptosis and Autophagy.

Cammalleri Maurizio M Locri Filippo F Catalani Elisabetta E Filippi Luca L Cervia Davide D Dal Monte Massimo M Bagnoli Paola P

Frontiers in cellular neuroscience 20171212

In a mouse model of oxygen induced retinopathy (OIR), beta adrenergic receptor (BAR) blockade has been shown to recover hypoxia-associated retinal damages. Although the adrenergic signaling is an important regulator of apoptotic and autophagic processes, the role of BARs in retinal cell death remains to be elucidated. The present study was aimed at investigating whether ameliorative effects of BAR blockers may occur through their coordinated action on apoptosis and autophagy. To this aim, retina ...[more]

PMID: 29375312

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Project description:Study objectivesPosttraumatic nightmares may exacerbate and perpetuate the daytime symptoms of posttraumatic stress disorder and might represent a therapeutic target. The therapeutic strategy of memory reconsolidation using the β-adrenergic receptor blocker propranolol associated with re-exposure psychotherapy is a promising treatment in patients with posttraumatic stress disorder. Previous studies have established this therapy is effective in reducing overall clinician-assessed posttraumatic stress disorder symptoms, but to date no previous study has specifically focused on posttraumatic nightmares in this therapy. This study provides a preliminary assessment of the evolution of nightmare severity during this therapy protocol compared with the decrease of the other posttraumatic stress disorder symptoms. It evaluates the incidence of side effects and examines the relative effects on posttraumatic nightmares.MethodsPatients were recruited as part of the Paris Mémoire Vive Study. Data were collected using a prospective longitudinal design including 1 baseline visit, 6 therapeutic visits, and 2 follow-up visits. During the 6 therapeutic visits, propranolol was administered orally 60 to 75 minutes prior to the psychotherapeutic session.ResultsOn average, nightmare severity decreased from "severe" to "mild" during the protocol and remained stable 2 months after the last session. Whereas 85% of patients reported nightmares at baseline, only 50% still had them after the protocol. The protocol was generally well tolerated and did not increase nightmare severity for any patient in the study.ConclusionsMemory reconsolidation therapy with propranolol seems promising in reducing nightmare severity, up to and including remission. However, research using a randomized controlled design and assessing maintenance of nightmare extinction is warranted.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: Using Reconsolidation Blockade to Treat Trauma Related Disorders After Paris Attacks: An Effectiveness Study (PARIS-MEM); Identifier: NCT02789982; URL: https://www.clinicaltrials.gov/ct2/show/NCT02789982.CitationMallet C, Chick CF, Maatoug R, Fossati P, Brunet A, Millet B. Memory reconsolidation impairment using the β-adrenergic receptor blocker propranolol reduces nightmare severity in patients with posttraumatic stress disorder: a preliminary study. J Clin Sleep Med. 2022;18(7):1847-1855.

Dataset Information

The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between Apoptosis and Autophagy.

Publications

The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between Apoptosis and Autophagy.

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