Schizophrenia-Like Features in Transgenic Mice Overexpressing Human HO-1 in the Astrocytic Compartment
| Autor: | Lalit K. Srivastava, Edith Hamel, Hyman M. Schipper, Wei Song, Adrienne Liberman, Xin Kang Tong, Sanjeev K. Bhardwaj, Jeannie Mui, Shih Hsiung Lin, Hojatollah Vali, Ayda Tavitian, Jacob R. Hascalovici, Hillel Zukor |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Dopamine Agents
Mice Monoaminergic Nuclear Receptor Subfamily 4 Group A Member 2 Laser-Doppler Flowmetry Reelin Prepulse inhibition Chromatography High Pressure Liquid Glial fibrillary acidic protein General Neuroscience Age Factors Brain Gene Expression Regulation Developmental Articles Sensory Gating Inhibition Psychological Benzamides alpha-Synuclein medicine.drug Protein Binding Tyrosine 3-Monooxygenase Enzyme-Linked Immunosorbent Assay Mice Transgenic Biology Nucleus accumbens Tritium Dopamine receptor D1 Downregulation and upregulation Dopamine Glial Fibrillary Acidic Protein medicine Animals Humans Biogenic Monoamines RNA Messenger Gait Disorders Neurologic Homeodomain Proteins Analysis of Variance Receptors Dopamine D2 Superoxide Dismutase Receptors Dopamine D1 Benzazepines Embryo Mammalian Disease Models Animal MicroRNAs Reelin Protein nervous system Acoustic Stimulation Animals Newborn Astrocytes biology.protein Schizophrenia Neuroscience Heme Oxygenase-1 Transcription Factors |
| Popis: | Delineation of key molecules that act epigenetically to transduce diverse stressors into established patterns of disease would facilitate the advent of preventive and disease-modifying therapeutics for a host of neurological disorders. Herein, we demonstrate that selective overexpression of the stress protein heme oxygenase-1 (HO-1) in astrocytes of novel GFAP.HMOX1 transgenic mice results in subcortical oxidative stress and mitochondrial damage/autophagy; diminished neuronal reelin content (males); induction of Nurr1 and Pitx3 with attendant suppression of their targeting miRNAs, 145 and 133b; increased tyrosine hydroxylase and α-synuclein expression with downregulation of the targeting miR-7b of the latter; augmented dopamine and serotonin levels in basal ganglia; reduced D1receptor binding in nucleus accumbens; axodendritic pathology and altered hippocampal cytoarchitectonics; impaired neurovascular coupling; attenuated prepulse inhibition (males); and hyperkinetic behavior. The GFAP.HMOX1 neurophenotype bears resemblances to human schizophrenia and other neurodevelopmental conditions and implicates glial HO-1 as a prime transducer of inimical (endogenous and environmental) influences on the development of monoaminergic circuitry. Containment of the glial HO-1 response to noxious stimuli at strategic points of the life cycle may afford novel opportunities for the effective management of human neurodevelopmental and neurodegenerative conditions. |
| Databáze: | OpenAIRE |
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