Role of Aspartyl-(asparaginyl)-β-hydroxylase Mediated Notch Signaling in Cerebellar Development and Function

Overview

Journal Behav Brain Funct

Publisher Biomed Central

Specialties Neurology
Psychology
Social Sciences

Date 2010 Nov 6

PMID 21050474

Citations 17

Authors

Elizabeth Silbermann

Peter Moskal

Nathaniel Bowling

Ming Tong

Suzanne M de la Monte

Affiliations

Soon will be listed here.

Abstract

Background: Aspartyl-(Asparaginyl)-β-Hydroxylase (AAH) is a hydroxylating enzyme that promotes cell motility by enhancing Notch-Jagged-HES-1 signaling. Ethanol impaired cerebellar neuron migration during development is associated with reduced expression of AAH.

Methods: To further characterize the role of AAH in relation to cerebellar development, structure, and function, we utilized an in vivo model of early postnatal (P2) intracerebro-ventricular gene delivery to silence AAH with small interfering RNA (siAAH), or over-express it with recombinant plasmid DNA (pAAH). On P20, we assessed cerebellar motor function by rotarod testing. Cerebella harvested on P21 were used to measure AAH, genes/proteins that mediate AAH's downstream signaling, i.e. Notch-1, Jagged-1, and HES-1, and immunoreactivity corresponding to neuronal and glial elements.

Results: The findings demonstrated that: 1) siAAH transfection impaired motor performance and blunted cerebellar foliation, and decreased expression of neuronal and glial specific genes; 2) pAAH transfection enhanced motor performance and increased expression of neuronal and glial cytoskeletal proteins; and 3) alterations in AAH expression produced similar shifts in Notch-1, Jagged-1, and HES-1 protein or gene expression.

Conclusions: The results support our hypothesis that AAH is an important mediator of cerebellar development and function, and link AAH expression to Notch signaling pathways in the developing brain.

Citing Articles

Impact of Prenatal Dietary Soy on Cerebellar Neurodevelopment and Function in Experimental Fetal Alcohol Spectrum Disorder.

de la Monte S, Tong M, Ziplow J, Mark P, Van S, Nguyen V Nutrients. 2025; 17(5).

PMID: 40077682 PMC: 11901751. DOI: 10.3390/nu17050812.

Differential rescue effects of choline chloride and soy isolate on metabolic dysfunction in immature central nervous system neurons: Relevance to fetal alcohol spectrum disorder.

de la Monte S, Elgas E, Tong M, Delikkaya B, Yang Y Diabetes Manag (Lond). 2024; 13(Suppl 1):107-118.

PMID: 39601020 PMC: 11595351.

Aspartate β-Hydroxylase Is Upregulated in Head and Neck Squamous Cell Carcinoma and Regulates Invasiveness in Cancer Cell Models.

Mukherjee P, Zhou X, Galli S, Davidson B, Zhang L, Ahn J Int J Mol Sci. 2024; 25(9).

PMID: 38732216 PMC: 11084744. DOI: 10.3390/ijms25094998.

Recent Advances and Therapeutic Implications of 2-Oxoglutarate-Dependent Dioxygenases in Ischemic Stroke.

Xie J, Zhang Z Mol Neurobiol. 2023; 61(7):3949-3975.

PMID: 38041714 DOI: 10.1007/s12035-023-03790-1.

Dietary Soy Prevents Alcohol-Mediated Neurocognitive Dysfunction and Associated Impairments in Brain Insulin Pathway Signaling in an Adolescent Rat Model.

Tong M, Ziplow J, Mark P, de la Monte S Biomolecules. 2022; 12(5).

PMID: 35625605 PMC: 9139005. DOI: 10.3390/biom12050676.

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