Fast-acting Antidepressant-like Effects of Reelin Evaluated in the Repeated-corticosterone Chronic Stress Paradigm

Overview

Journal Neuropsychopharmacology

Date 2020 Jan 12

PMID 31926481

Citations 18

Authors

Kyle J Brymer

Jenessa Johnston

Justin J Botterill

Raquel Romay-Tallon

Milann A Mitchell

Josh Allen

Graziano Pinna

Hector J Caruncho

Lisa E Kalynchuk

Affiliations

Soon will be listed here.

Abstract

The present report examines the effects of repeated or single intrahippocampal Reelin infusions on measures of depressive-like behavior, cognition, and hippocampal neurogenesis in the repeated-corticosterone (CORT) paradigm. Rats received subcutaneous injections of CORT for 3 weeks and Reelin was infused through an inserted canula in the left hippocampus on days 7, 14, and 21, or only on day 21 of CORT injections. CORT increased immobility in the forced-swim test and impaired object-location memory. Notably, these effects were reversed by both repeated and single-Reelin infusions. CORT decreased both the number and complexity of doublecortin-labeled maturing newborn neurons in the dentate gyrus subgranular zone, and a single-Reelin infusion increased the number but not complexity of newborn neurons, while repeated Reelin infusions restored both. Injection of the AMPA antagonist CNQX blocked the rescue of the behavioral phenotype by Reelin but did completely block the effects of Reelin on hippocampal neurogenesis. Reelin is able to rescue the deficits in AMPA, NMDA, GABA receptors, mTOR and p-mTOR induced by CORT. These novel results demonstrate that a single intrahippocampal Reelin infusion into the dorsal hippocampus has fast-acting antidepressant-like effects, and that some of these effects may be at least partially independent of Reelin actions on hippocampal neurogenesis.

Citing Articles

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A single intravenous reelin injection restores corticosterone-induced neurochemical and behavioral alterations in dams during the post-partum period.

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The Inflammation-Induced Dysregulation of Reelin Homeostasis Hypothesis of Alzheimer's Disease.

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Intravenous Reelin rescues despair-like behavior, Reelin cells in the dentate sub-granular zone, and spleen atrophy in the cyclic corticosterone model of recurring depressive episodes.

Reive B, Johnston J, Sanchez-Lafuente C, Scheil K, Kurz K, Kalynchuk L Front Pharmacol. 2024; 15:1368620.

PMID: 38482060 PMC: 10936541. DOI: 10.3389/fphar.2024.1368620.

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