Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry

Marta Pratelli; Sara Migliarini; Barbara Pelosi; Francesco Napolitano; Alessandro Usiello; Massimo Pasqualetti

doi:10.1523/ENEURO.0376-16.2017

Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry

eNeuro. 2017 Apr 11;4(2):ENEURO.0376-16.2017. doi: 10.1523/ENEURO.0376-16.2017. eCollection 2017 Mar-Apr.

Authors

Marta Pratelli¹, Sara Migliarini¹, Barbara Pelosi¹, Francesco Napolitano^{2

3}, Alessandro Usiello^{2

4}, Massimo Pasqualetti^{1

5

6}

Affiliations

¹ Department of Biology Unit of Cell and Developmental Biology, University of Pisa, Pisa 56127, Italy.
² Ceinge Biotecnologie Avanzate, Naples 80145, Italy.
³ Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy.
⁴ Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania, Luigi Vanvitelli, Italy.
⁵ Center for Neuroscience and Cognitive Systems, Istituto Italiano di Tecnologia, Rovereto, TN 38068, Italy.
⁶ Neuroscience Institute, National Research Council (CNR), Pisa 56124, Italy.

Abstract

Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the fine-tuning of neuron development and the establishment of wiring patterns in the brain. However, whether serotonin is involved in the maintenance of neuronal circuitry in the adult brain remains elusive. Here, we use a Tph2^fl°^x conditional knockout (cKO) mouse line to assess the impact of serotonin depletion during adulthood on serotonergic system organization. Data show that the density of serotonergic fibers is increased in the hippocampus and decreased in the thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin depletion. Strikingly, these defects are rescued following reestablishment of brain 5-HT signaling via administration of the serotonin precursor 5-hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers reveals that changes in serotonin homeostasis affect axonal branching complexity. These data demonstrate that maintaining proper serotonin homeostasis in the adult brain is crucial to preserve the correct serotonergic axonal wiring.

Keywords: 5-hydroxytryptophan; serotonergic innervations; serotonin; serotonin homeostasis; tryptophan hydroxylase 2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

5-Hydroxytryptophan / pharmacology
Animals
Brain-Derived Neurotrophic Factor / genetics
Brain-Derived Neurotrophic Factor / metabolism
Gene Expression Regulation / drug effects
Gene Expression Regulation / genetics
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Homeostasis / drug effects
Homeostasis / genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Midline Thalamic Nuclei / cytology*
Nerve Net / physiology*
Neural Pathways / drug effects
Neural Pathways / physiology
RNA, Messenger / metabolism
Serotonergic Neurons / drug effects
Serotonergic Neurons / physiology*
Serotonin / metabolism*
Serotonin Agents / pharmacology
Serotonin Plasma Membrane Transport Proteins / genetics
Serotonin Plasma Membrane Transport Proteins / metabolism
Signal Transduction / drug effects
Signal Transduction / genetics
Tryptophan Hydroxylase / genetics
Tryptophan Hydroxylase / metabolism

Substances

Brain-Derived Neurotrophic Factor
RNA, Messenger
Serotonin Agents
Serotonin Plasma Membrane Transport Proteins
Green Fluorescent Proteins
Serotonin
5-Hydroxytryptophan
Tph2 protein, mouse
Tryptophan Hydroxylase