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Antidepressant-like effect of artemin in mice: a mechanism for acetyl-l-carnitine activity on depression

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Abstract

Rationale

Depression may be associated with altered plasticity of the nervous system. The importance of neurotrophic factor levels is strongly suggested, and the neuronal-related family is extensively studied with respect to glial-derived one.

Objectives

Aimed to contribute to the study of nervous plasticity modulation as therapeutical target in mood disorders, the role of the glial-derived factor artemin (ARTN) in depression and in the pharmacodynamics of the antidepressant and trophic compound acetyl-l-carnitine (ALCAR) was evaluated.

Methods

Male mice were treated with 100 mg kg−1 ALCAR daily for 7 days; 0.6 μg/mouse ARTN was acutely injected intracerebroventricularly. Gene knockdown of ARTN and GDNF family receptor alpha (GFRalpha3) was obtained by oligonucleotide antisense strategy. The forced swimming test was performed to evaluate antidepressant-like effects.

Results

Repeated ALCAR administration increased ARTN levels in spinal cord, hippocampus, and prefrontal cortex. No modulatory effect was detected on BDNF and glial cell line-derived neutrotrophic factor (GDNF). ARTN, 30 min after administration, showed a dose-dependent antidepressant-like effect. ALCAR needed a 7-day treatment to reach a comparable effect; nevertheless, both substances were able to induce a phosphorylation of the GDNF family receptor Ret. A decrease of the free ARTN level by a specific ARTN antibody impaired the antidepressant-like effect of acute ARTN and repeated ALCAR. Gene knockdown of ARTN or, alternatively, of its receptor GFRalpha3 fully prevented ALCAR effectiveness.

Conclusions

A mechanism for the antidepressant property of ALCAR is proposed, and the novelty of the possible role of ARTN in depression is suggested.

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Acknowledgments

The authors declare that this work was funded by the Italian Ministry of Instruction, University and Research and by Sigma-Tau Industrie Farmaceutiche Riunite.

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Authors and Affiliations

  1. Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy

    Lorenzo Di Cesare Mannelli, Elisa Vivoli, Alberto Salvicchi, Alessandro Bartolini & Carla Ghelardini

  2. Department of Experimental Pathology and Oncology, University of Florence, Viale Morgagni 85, 50134, Florence, Italy

    Nicola Schiavone

  3. Sigma-Tau Industrie Farmaceutiche Riunite S.p.A, Via Pontina km 30,400, 00040, Pomezia, Rome, Italy

    Aleardo Koverech, Masa Messano, Raffaella Nicolai & Paola Benatti

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  1. Lorenzo Di Cesare Mannelli
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  2. Elisa Vivoli
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  3. Alberto Salvicchi
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  9. Alessandro Bartolini
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Correspondence to Lorenzo Di Cesare Mannelli.

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Di Cesare Mannelli, L., Vivoli, E., Salvicchi, A. et al. Antidepressant-like effect of artemin in mice: a mechanism for acetyl-l-carnitine activity on depression. Psychopharmacology 218, 347–356 (2011). https://doi.org/10.1007/s00213-011-2326-0

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