1. Pharmacological treatment with mirtazapine rescues cortical atrophy and respiratory deficits in MeCP2 null mice
- Author
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Valentina Vaghi, Gabriele Baj, Sara Ferrazzo, Enrico Tongiorgi, Carlo Antonio Raminelli, Annalisa Bernareggi, Tamara Bittolo, Chiara Deiana, Bittolo, Tamara, Raminelli, Carlo Antonio, Deiana, Chiara, Baj, Gabriele, Vaghi, Valentina, Ferrazzo, Sara, Bernareggi, Annalisa, and Tongiorgi, Enrico
- Subjects
0301 basic medicine ,Methyl-CpG-Binding Protein 2 ,Mice ,0302 clinical medicine ,Heart Rate ,Desipramine ,Medicine ,GABAergic Neurons ,gamma-Aminobutyric Acid ,Cerebral Cortex ,Multidisciplinary ,Seizure ,Antidepressive Agents ,medicine.anatomical_structure ,Breath Tests ,Cerebral cortex ,Anesthesia ,Antidepressant ,GABAergic ,Antidepressive Agent ,medicine.drug ,Human ,medicine.medical_specialty ,Breath Test ,congenital, hereditary, and neonatal diseases and abnormalities ,Mirtazapine ,Rett syndrome ,Mianserin ,Article ,MECP2 ,03 medical and health sciences ,Seizures ,Internal medicine ,Rett Syndrome ,Animals ,Humans ,GABAergic Neuron ,Atrophy ,Somatosensory Cortex ,business.industry ,Animal ,medicine.disease ,030104 developmental biology ,Endocrinology ,Monoamine neurotransmitter ,business ,030217 neurology & neurosurgery - 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.
- Published
- 2016