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Postnatal alterations in dopaminergic markers in the human prefrontal cortex
C S Weickert1, M J Webster, P Gondipalli
1Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, 9000 Rockville Boulevard, Building 10, CRC6-5340, Bethesda, MD 20892, USA.
Neuroscience
|November 25, 2006
Summary
Dopamine system markers in the human prefrontal cortex change significantly after birth. Dopamine receptor 1 (DAR1) and dopamine receptor 2 (DAR2) levels peak in infancy or adolescence, respectively, and decline with age.
Area of Science:
- Neuroscience
- Developmental Biology
- Neurochemistry
Background:
- Dopamine in the prefrontal cortex is vital for cognition and implicated in neuropsychiatric disorders.
- The postnatal development of the human prefrontal cortex dopaminergic system is not well understood.
Purpose of the Study:
- To investigate the developmental trajectory of pre- and post-synaptic dopaminergic markers in the human prefrontal cortex throughout the lifespan.
- To correlate developmental changes with potential implications for neuropsychiatric disorders.
Main Methods:
- Analysis of postmortem prefrontal cortex tissue from 37 individuals (2 months to 86 years).
- Quantification of tyrosine hydroxylase (dopamine biosynthesis enzyme) via Western immunoblotting.
- Assessment of dopamine receptor 1 (DAR1), DAR2, and DAR4 gene expression using in situ hybridization.
Main Results:
- Tyrosine hydroxylase and DAR2 mRNA levels were highest in neonates.
- DAR1 mRNA expression peaked in adolescents and young adults.
- DAR1 and DAR2 mRNA levels were reduced in aged individuals; DAR4 mRNA showed no significant age-related changes.
Conclusions:
- The human prefrontal cortex dopaminergic system undergoes dynamic pre- and post-synaptic changes during postnatal development.
- The adolescent peak in DAR1 mRNA may be relevant to the onset of disorders like schizophrenia.
