Experimental studies indicate that
hypoxia to the fetus, a common occurrence in many birth complications in humans, results in long-term disturbances of the central dopaminergic (DA) systems that persist in adulthood. Because dysregulation of DA systems is involved in the pathophysiology of many neurological and
psychiatric disorders, we investigated the effects of perinatal
hypoxia on the mesencephalic DA neurons of the human neonate using immunohistochemistry. We studied the expression of
tyrosine hydroxylase (TH), the first and rate-limiting
enzyme in
catecholamine synthesis, in substantia nigra, and ventral tegmental area of 18 neonates in relation to the age and severity/duration of hypoxic injury estimated by neuropathological criteria. In severe/abrupt perinatal
hypoxia, intense TH staining was observed in substantia nigra, ventral tegmental area, and, surprisingly, in the nonpreganglionic Edinger-Westphal nucleus. In severe/prolonged
hypoxia, there was a striking reduction or even absence of TH immunoreactivity in all the mesencephalic nuclei. These observations suggest that at early states of perinatal
hypoxia, there is a massive increase in
dopamine synthesis and release that is followed by feedback blockage of
dopamine synthesis through inhibition of TH by the end product
dopamine. Early dysregulation of DA neurotransmission could predispose infant survivors of severe perinatal
hypoxia to
dopamine-related neurological and/or cognitive deficits later in life.