| First Author | Song W | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 32 | Pages | 10841-53 |
| PubMed ID | 22875919 | Mgi Jnum | J:186620 |
| Mgi Id | MGI:5432812 | Doi | 10.1523/JNEUROSCI.6469-11.2012 |
| Citation | Song W, et al. (2012) Schizophrenia-Like Features in Transgenic Mice Overexpressing Human HO-1 in the Astrocytic Compartment. J Neurosci 32(32):10841-10853 |
| abstractText | 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 alpha-synuclein expression with downregulation of the targeting miR-7b of the latter; augmented dopamine and serotonin levels in basal ganglia; reduced D(1) receptor 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. |
