Abstract Details

Title An 'HO-1 Transducer' Model of Developmental and Degenerative Brain Disorders

Topic Child Neurology/Developmental Neurobiology

Presentation(s) S15 - (-)

Poster/Presentation
Number 006

Objective

Background 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. We previously showed that transfection of cultured astroglia with HMOX1 elicits cytopathological changes akin to those observed in human neurodevelopmental and degenerative disorders and renders nearby neurons vulnerable to oxidative injury.

Design/Methods GFAP.HMOX1 transgenic mice were engineered to overexpress human HO-1 in the astrocytic compartment.

Results At 48 weeks of age, GFAP.HMOX1 transgenic mice exhibited subcortical oxidative stress and mitochondrial damage/autophagy; diminished neuronal reelin content (males); induction of Nurr1 and Pitx3; increased tyrosine hydroxylase and_?-synuclein expression; augmented dopamine and serotonin levels in basal ganglia; reduced D1 receptor binding in nucleus accumbens; axodendritic pathology and altered hippocampal cytoarchitectonics; impaired neurovascular coupling; attenuated prepulse inhibition (males); and hyperkinetic behavior.

Conclusions 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.

Authors/Disclosures
PRESENTER	No disclosure on file
Wei Song (Lady Davis Institute for Medical Research)	No disclosure on file
Hillel Zukor (Lady Davis Institute for Medical Research)	No disclosure on file
	No disclosure on file
Jacob R. Hascalovici, MD (Montefiore Medical Center)	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
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	No disclosure on file
Hyman M. Schipper, MD, PhD, FAAN (Jewish General Hospital)	No disclosure on file

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