Dopaminergic System: The Role Of Aging In The Brain

Aging in the brain is a complex process that involves several systems and structures. Normal aging not only shows a decreased activity in neurotransmission, but also is a major risk factor for the development of neurodegenerative diseases. Dysfunction of the central noradrenergic and dopaminergic systems is one of the biological characteristics of aging, which may contribute to changes in cognitive and motor functions in aged persons. Furthermore, aging-dependent norepinephrine (NE) loss occurs earlier than that of dopamine (DA) and a functional noradrenergic system may influence the dopaminergic activities evidenced by the fact that an intact noradrenergic system shows neuroprotection on nigrostriatal dopaminergic neurons, and endogenous NE
In the past decade, substantial progress has been made in uncovering critical effects of transcription factors such as Phox2a, Phox2b, Hand2 and Gata3 on noradrenergic neurons. It is now well known that during the embryonic period, these transcription factors coordinately control the specification and differentiation of noradrenergic neurons. Recent years’ studies have shown that these transcription factors have a potential regulatory role of noradrenergic neurons in adult brains. For example, all four transcription factors are present in fully differentiated noradrenergic neurons in the brain throughout lifetime. Furthermore, these transcription factors are required for maintenance of mature noradrenergic neurons in vivo and for continued expression of DA
Likewise, administration of a NE precursor, and noradrenergic receptor antagonists and agonists will work similarly. The restored noradrenergic function will facilitate the functional improvement of the DA system. Accordingly, the results of the current study may provide new insights into the correlation between these transcription factor genes and LC neuronal dysfunction during aging and further affect the dopaminergic