Prenatal one-carbon metabolism dysregulation programs schizophrenia-like deficits
| Autor: | A R Hamzeh, Nayna Sanathara, S M Lee, Zitong Wang, Ryan F. Yoshimura, Xiangmin Xu, Lien Wang, Amal Alachkar, Olivier Civelli, Geoffrey W. Abbott |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Developmental Disabilities Medical and Health Sciences Mice 0302 clinical medicine Methionine Pregnancy Haloperidol Basic Helix-Loop-Helix Transcription Factors Hippocampal 2.1 Biological and endogenous factors Aetiology Prefrontal cortex Clozapine Tetrahydrofolates Psychiatry Neuronal Plasticity Neurogenesis CA1 Region Biological Sciences Psychiatry and Mental health Mental Health Prenatal Exposure Delayed Effects Neurological Female Psychology medicine.drug Antipsychotic Agents medicine.medical_specialty Prefrontal Cortex Article 03 medical and health sciences Cellular and Molecular Neuroscience Folic Acid Internal medicine Neuroplasticity Genetics medicine Animals Humans Molecular Biology CA1 Region Hippocampal One-Carbon Group Transferases Animal Psychology and Cognitive Sciences Neurosciences medicine.disease Brain Disorders Developmental disorder Stereotypy (non-human) Disease Models Animal 030104 developmental biology Endocrinology Disease Models Synaptic plasticity Schizophrenia Stereotyped Behavior Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Alachkar, A; Wang, L; Yoshimura, R; Hamzeh, AR; Wang, Z; Sanathara, N; et al.(2018). Prenatal one-carbon metabolism dysregulation programs schizophrenia-like deficits. MOLECULAR PSYCHIATRY, 23(2), 282-294. doi: 10.1038/mp.2017.164. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/2wh1n4k9 Molecular psychiatry, vol 23, iss 2 |
| Popis: | The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equivalent to double their daily intake during the last week of gestation. Their progeny (MET mice) exhibited schizophrenia-like social deficits, cognitive impairments and elevated stereotypy, decreased neurogenesis and synaptic plasticity, and abnormally reduced local excitatory synaptic connections in CA1 neurons. Neural transcript expression of only one gene, encoding the Npas4 transcription factor, was >twofold altered (downregulated) in MET mice; strikingly, similar Npas4 downregulation occurred in the prefrontal cortex of human patients with schizophrenia. Finally, therapeutic actions of typical (haloperidol) and atypical (clozapine) antipsychotics in MET mice mimicked effects in human schizophrenia patients. Our data support the validity of MET mice as a model for schizophrenia, and uncover methionine metabolism as a potential preventive and/or therapeutic target. |
| Databáze: | OpenAIRE |
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