The Dopaminergic System

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Aging in the brain is a complex process that involves several systems and structures. As the brain ages, there is a decreased activity in neurotransmission and increased risk for the development of neurodegenerative diseases. Dysfunction of the central noradrenergic and dopaminergic systems is one of the biological characteristics of aging in the brain and may contribute to changes in cognitive and motor functions in old individuals. Furthermore, aging-dependent norepinephrine (NE) loss occurs earlier than that of dopamine (DA) and a functional noradrenergic system may influence dopaminergic activities as evidenced by the fact that an intact noradrenergic system is neuroprotective on nigrostriatal dopaminergic neurons, and endogenous NE …show more content…
Therefore, manipulation of the noradrenergic system may not only improve aging-related dysfunction in the noradrenergic system, but also those of the dopaminergic system. Substantial progress has been made in uncovering critical effects of the transcription factors Phox2a, Phox2b, Hand2 and Gata3 on noradrenergic neurons in the past decade. It is now well known that during the embryonic period, these transcription factors coordinately control the specification and differentiation of noradrenergic neurons. These transcription factors have a potential regulatory role on noradrenergic neurons in the adult brain. For example, all four transcription factors are always present in fully differentiated noradrenergic neurons in the brain. Furthermore, they are required for the maintenance of mature noradrenergic neurons in vivo and for the continued expression of DA β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in …show more content…
Likewise, the administration of a NE precursor, and noradrenergic receptor antagonists and agonists will achieve the same effect. Restored noradrenergic function will facilitate functional improvements in the DA system. Therefore, results from the current study will likely provide new insights into the correlation between these transcription factor genes and LC neuronal dysfunction during aging and further improve dopaminergic

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