Dataset Information

Opposing effects of ?2- and ?-adrenergic receptor stimulation on quiescent neural precursor cell activity and adult hippocampal neurogenesis.

ABSTRACT: Norepinephrine regulates latent neural stem cell activity and adult hippocampal neurogenesis, and has an important role in modulating hippocampal functions such as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage process, spanning from the activation and proliferation of hippocampal stem cells, to their differentiation into neurons. However, the stage-specific effects of noradrenergic receptors in regulating adult hippocampal neurogenesis remain poorly understood. In this study, we used transgenic Nestin-GFP mice and neurosphere assays to show that modulation of ?2- and ?-adrenergic receptor activity directly affects Nestin-GFP/GFAP-positive precursor cell population albeit in an opposing fashion. While selective stimulation of ?2-adrenergic receptors decreases precursor cell activation, proliferation and immature neuron number, stimulation of ?-adrenergic receptors activates the quiescent precursor pool and enhances their proliferation in the adult hippocampus. Furthermore, our data indicate no major role for ?1-adrenergic receptors, as we did not observe any change in either the activation and proliferation of hippocampal precursors following selective stimulation or blockade of ?1-adrenergic receptors. Taken together, our data suggest that under physiological as well as under conditions that lead to enhanced norepinephrine release, the balance between ?2- and ?-adrenergic receptor activity regulates precursor cell activity and hippocampal neurogenesis.

SUBMITTER: Jhaveri DJ

PROVIDER: S-EPMC4055446 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Opposing effects of α2- and β-adrenergic receptor stimulation on quiescent neural precursor cell activity and adult hippocampal neurogenesis.

Jhaveri Dhanisha J DJ Nanavaty Ishira I Prosper Boris W BW Marathe Swanand S Husain Basma F A BF Kernie Steven G SG Bartlett Perry F PF Vaidya Vidita A VA

PloS one 20140612 6

Norepinephrine regulates latent neural stem cell activity and adult hippocampal neurogenesis, and has an important role in modulating hippocampal functions such as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage process, spanning from the activation and proliferation of hippocampal stem cells, to their differentiation into neurons. However, the stage-specific effects of noradrenergic receptors in regulating adult hippocampal neurogenesis remain poorly understood. In th ...[more]

PMID: 24922313

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Project description:Neurogenesis persists in the subgranular zone of the hippocampal formation in the adult mammalian brain. In this area, neural progenitor cells (NPCs) receive both permissive and instructive signals, including neurotransmitters, that allow them to generate adult-born neurons which can be functionally integrated in the preexisting circuit. Deregulation of adult hippocampal neurogenesis (ahNG) occurs in several neuropsychiatric and neurodegenerative diseases, including major depression, and represents a potential therapeutic target. Of interest, several studies suggested that, both in rodents and in humans, ahNG is increased by chronic administration of classical monoaminergic antidepressant drugs, suggesting that modulation of this process may participate to their therapeutic effects. Since the established observation that noradrenergic innervations from locus coeruleus make contact with NPC in the dentate gyrus, we investigated the role of beta adrenergic receptor (?-AR) on ahNG both in vitro and in vivo. Here we report that, in vitro, activation of ?2-AR by norepinephrine and ?2-AR agonists promotes the formation of NPC-derived mature neurons, without affecting NPC survival or differentiation toward glial lineages. Additionally, we show that a selective ?2-AR agonist able to cross the blood-brain barrier, salmeterol, positively modulates hippocampal neuroplasticity when chronically administered in adult naïve mice. Indeed, salmeterol significantly increased number, maturation, and dendritic complexity of DCX+ neuroblasts. The increased number of DCX+ cells was not accompanied by a parallel increase in the percentage of BrdU+/DCX+ cells suggesting a potential prosurvival effect of the drug on neuroblasts. More importantly, compared to vehicle, salmeterol promoted ahNG, as demonstrated by an increase in the actual number of BrdU+/NeuN+ cells and in the percentage of BrdU+/NeuN+ cells over the total number of newly generated cells. Interestingly, salmeterol proneurogenic effects were restricted to the ventral hippocampus, an area related to emotional behavior and mood regulation. Since salmeterol is commonly used for asthma therapy in the clinical setting, its novel pharmacological property deserves to be further exploited with a particular focus on drug potential to counteract stress-induced deregulation of ahNG and depressive-like behavior.

Dataset Information

Opposing effects of ?2- and ?-adrenergic receptor stimulation on quiescent neural precursor cell activity and adult hippocampal neurogenesis.

Publications

Opposing effects of α2- and β-adrenergic receptor stimulation on quiescent neural precursor cell activity and adult hippocampal neurogenesis.

Similar Datasets

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