title: Pharmacological treatment with mirtazapine rescues cortical atrophy and respiratory deficits in MeCP2 null mice.
abstract: Loss of MeCP2 (Methyl CpG binding protein 2) in Rett syndrome (RTT) causes brain weight decrease, shrinkage of the cortex with reduced dendritic arborization, behavioral abnormalities, seizures and cardio-respiratory complications. The observed monoamine neurotransmitters reduction in RTT suggested antidepressants as a possible therapy. We treated MeCP2-null mice from postnatal-day 28 for two weeks with desipramine, already tested in RTT, or mirtazapine, an antidepressant with limited side-effects, known to promote GABA release. Mirtazapine was more effective than desipramine in restoring somatosensory cortex thickness by fully rescuing pyramidal neurons dendritic arborization and spine density. Functionally, mirtazapine treatment normalized heart rate, breath rate, anxiety levels, and eliminated the hopping behavior observed in MeCP2-null mice, leading to improved phenotypic score. These morphological and functional effects of mirtazapine were accompanied by reestablishment of the GABAergic and glutamatergic receptor activity recorded in cortex and brainstem tissues. Thus, mirtazapine can represent a new potential pharmacological treatment for the Rett syndrome.
authors.affiliation: Department of Life Sciences, University of Trieste, Via L. Giorgieri, 5-34127 Trieste, Italy.
authors.forename: Tamara
authors.initials: T
authors.lastname: Bittolo
authors.affiliation: Department of Life Sciences, University of Trieste, Via L. Giorgieri, 5-34127 Trieste, Italy.
authors.forename: Carlo Antonio
authors.initials: CA
authors.lastname: Raminelli
authors.affiliation: Department of Life Sciences, University of Trieste, Via L. Giorgieri, 5-34127 Trieste, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Deiana
authors.affiliation: Department of Life Sciences, University of Trieste, Via L. Giorgieri, 5-34127 Trieste, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Baj
authors.affiliation: Department of Life Sciences, University of Trieste, Via L. Giorgieri, 5-34127 Trieste, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vaghi
authors.affiliation: Department of Life Sciences, University of Trieste, Via L. Giorgieri, 5-34127 Trieste, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrazzo
authors.affiliation: Department of Life Sciences, University of Trieste, Via L. Giorgieri, 5-34127 Trieste, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Bernareggi
authors.affiliation: Department of Life Sciences, University of Trieste, Via L. Giorgieri, 5-34127 Trieste, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Tongiorgi
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001284:Atrophy / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D001944:Breath Tests; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D003891:Desipramine / Q000008:administration & dosage; D059330:GABAergic Neurons / Q000187:drug effects / Q000473:pathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D008803:Mianserin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051379:Mice; D000078785:Mirtazapine; D015518:Rett Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012640:Seizures / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D013003:Somatosensory Cortex / Q000187:drug effects / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000235:genetics / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D051783:Methyl-CpG-Binding Protein 2; D008803:Mianserin; D005680:gamma-Aminobutyric Acid; D000078785:Mirtazapine; D003891:Desipramine