The Human Neurosecretory Neurones Under Perinatal Hypoxia: A Quantitative Immunohistochemical Study of the Supraoptic Nucleus in Autopsy Material

Abstract

In the rat, experimental manipulations that cause activation of the magnocellular neurosecretory neurones result in the synthesis, in addition to vasopressin (AVP) and oxytocin (OXY), of other neurotransmitters or peptides, including tyrosine hydroxylase (TH), the first and rate limiting enzyme for catecholamine biosynthesis. In the human neonate, our previous study showed that TH was selectively increased in AVP neurones of subjects that died from prolonged perinatal hypoxia. The purpose of the present study was to quantitatively investigate the expression of TH, AVP, OXY and neurophysin in magnocellular neurones of the human neonate in relation to the severity/duration of perinatal hypoxia, as estimated by neuropathological criteria. Autopsy was performed after obtaining parental written consent for diagnostic and research purposes. The intensity of the immunohistochemical reactions and the cellular/nuclear size were measured in the dorsolateral supraoptic nucleus using a computerised image analysis system. We showed that prolonged perinatal hypoxia resulted in the activation of the magnocellular neuroendocrine neurones of the human neonate, as indicated by their increased neuronal and nuclear size. OXY neurones appeared larger than the AVP ones at birth, possibly indicating an active role of foetal OXY during labour or even earlier. The gradual increase in the duration of the insult resulted in the reduction of intracellular AVP content, in parallel with a dramatic increase in the expression of TH, indicating a functional interaction of these peptides under neuronal activation. Ιsolated evidence in our series, obtained from an infant of a diabetic mother, raises the probability that in the case of hyperglycaemia the above pathogenetic mechanisms are diversified.

The Effect of Perinatal Hypoxic/Ischemic Injury on Tyrosine Hydroxylase Expression in the Locus Coeruleus of the Human Neonate

“…In 2 out of 5 subjects, low TH immunoreactivity was observed, while in the remaining 3 cases, intense TH staining was revealed in the LC, similar to the pattern of HII group 1 subjects with acute lesions. It is of note that such differences in the number and intensity of TH-IR perikarya among subjects of the same HII group were not evident in the other brain areas containing TH-IR neurons studied in our previous investigations in both the mesencephalon [16] and the hypothalamus of the same series of neonates [41,42]. Notably, in our previous study the magnocellular neurosecretory neurons in the hypothalamus appeared to induce TH expression under prolonged or chronic hypoxic damage in all the cases of group 3 [42].…”

“…It is of note that such differences in the number and intensity of TH-IR perikarya among subjects of the same HII group were not evident in the other brain areas containing TH-IR neurons studied in our previous investigations in both the mesencephalon [16] and the hypothalamus of the same series of neonates [41,42]. Notably, in our previous study the magnocellular neurosecretory neurons in the hypothalamus appeared to induce TH expression under prolonged or chronic hypoxic damage in all the cases of group 3 [42]. The discordance in TH staining of LC neurons within HII group 3 is of unclear significance, in view also of the small subgroups of patients that do not allow safe conclusions to be drawn.…”

“…The observed reduction in cell size, as well as in TH expression, appears to be functional and unrelated to factors such as the postmortem delay or fixation time of the tissues since in the hypothalamus of the same subjects, a dramatic increase in the neuronal size and induction of TH expression was observed likely due to activation of neurosecretory neurons after prolonged perinatal hypoxia [41,42]. Chronic hypoxia causes an adaptive reduction in metabolism [77] and an increase in the number of α 2 -somatodendritic inhibitory autoreceptors in the LC [78], events that may contribute to the observed reduction in cell size, as well as to the reduction in TH staining in LC neurons of neonates with changes of prolonged, older or chronic HII.…”

“…Part of this material was also used in our previous studies concerning the effect of perinatal hypoxia on the neurosecretory neurons of the hypothalamus [41,42] and the dopaminergic neurons of the mesencephalon [16,43]. Complete postmortem examination was carried out in all cases after parental written consent for diagnostic and research purposes.…”

Distribution of tyrosine‐hydroxylase‐immunoreactive neurons in the hypothalamus of tree shrews

“…A differential expression of TH immunoreactivity in neurosecretory neurons of the human PVN and SON is positively correlated with AVP mRNA levels (Panayotacopoulou et al, ). In addition, in the hypothalamus of the human neonate, TH expression has been observed to increase dramatically in newborns that have suffered prolonged perinatal hypoxia (Ganou et al, ; Pagida et al, ). TH is an oxygen‐dependent enzyme catalyzing the initial rate‐limiting step in catecholaminergic synthesis, and hypoxia is a major regulator of its expression (Ganou et al, ).…”