Increased Expression of Tyrosine Hydroxylase Immunoreactivity in Paraventricular and Supraoptic Neurons in Illnesses with Prolonged Osmotic or Nonosmotic Stimulation of Vasopressin Release

Abstract

Our previous studies indicated that in the human paraventricular (PVN) and supraoptic (SON) nuclei, tyrosine hydroxylase (TH) – the first and rate-limiting enzyme in catecholamine synthesis – is localized mainly in magnocellular neurons and that antemortem factors regulate its expression. The purpose of the present study was to investigate the distribution of TH-immunoreactive (TH-IR) perikarya of the hypothalami of a large sample of well-documented adult subjects without neurological, psychiatric or endocrinological disease in order to identify factors that could regulate the expression of TH in the human neurosecretory neurons. Our material consisted of the hypothalami of 38 subjects studied immunohistochemically for TH using the peroxidase-antiperoxidase method. Striking individual differences were observed among the subjects studied concerning the number and distribution of TH-IR perikarya within the PVN and SON. These differences were evident throughout the entire rostrocaudal length of the hypothalamus and appeared to be related neither to the age or sex of the subjects nor to the postmortem interval or staining procedures. In the sample studied, a large number of TH-IR perikarya were observed specifically in all subjects that had suffered from right-sided heart failure due to pulmonary hypertension, liver cirrhosis or dehydration. In all the above illnesses, increased production and secretion of vasopressin (VP) are reported to occur due to a decrease in ‘effective’ blood volume or to osmotic stimulation. We conclude that somatic illnesses leading to prolonged osmotic or nonosmotic stimulation of VP release may induce increased expression of TH immunoreactivity in the human neurosecretory neurons related to neuronal activation.

Absence of a Difference in the Neurosecretory Activity of Supraoptic Nucleus Vasopressin Neurons of Neuroleptic-Treated Schizophrenic Patients

“…Similarly, no significant differences in TH expression were detected in the substantia nigra between schizophrenics and controls by reverse transcription-polymerase chain reaction [45]. The interindividual variability in TH expression could be attributed to somatic illnesses that may affect the activity of the VP neurons through osmotic and nonosmotic stimuli [19]. Indeed, the cases with the largest number of TH-IR neurons in our sample are NBB 92075 – a schizophrenic patient suffering from pulmonary hypertension/cor pulmonale – and NBB 94074 – a control subject who suffered from cardiac decompensation – i.e., both cases suffering from somatic illnesses that lead to nonosmotic stimulation of VP release due to a decrease in ‘effective’ blood volume [46,47,48].…”

“…We also studied the expression of tyrosine hydroxylase (TH) – the first and rate-limiting enzyme for dopamine synthesis, a neurotransmitter highly implicated in the pathophysiology of schizophrenia [17, 18]. In our previous study on mentally healthy subjects [19,] TH was found to be overexpressed in the VP neurons under clinical conditions of prolonged osmotic or nonosmotic stimulation. We focused our study on the dorsolateral part of the supraoptic nucleus (dl-SON), since this is the main source of plasma VP, and about 95% of its neurons synthesize VP in humans [20].…”

Individual Differences in the Expression of Tyrosine Hydroxylase mRNA in Neurosecretory Neurons of the Human Paraventricular and Supraoptic Nuclei: Positive Correlation with Vasopressin mRNA

“…In a number of previous studies [3,4,5,6,7,] we described striking individual differences concerning the number and distribution of TH-IR neurons in PVN and SON among control subjects, i.e., cases without known neurological, psychiatric, or endocrinological illnesses. These differences were evident throughout the entire rostrocaudal length of PVN and SON and appeared to be related neither to age or sex of the subjects nor to postmortem interval or staining procedures.…”

“…We attributed these individual differences to antemortem factors that could influence the expression of the TH gene within the human neurosecretory neurons. Since a large number of TH-IR perikarya was observed specifically in subjects that had suffered from somatic illnesses, leading to prolonged osmotic or nonosmotic stimulation of VP release (i.e., dehydration, right-sided heart failure due to pulmonary hypertension, or liver cirrhosis), we suggested that the expression of TH within the human neurosecretory nuclei is related to the activation of VP neurons [7]. …”

Reduced Immunoreactivity of Tyrosine Hydroxylase in the Hypothalamic Paraventricular Nucleus of the Seizure Sensitive Gerbil

“…TH activities in the central and peripheral nervous systems are subject to changes in stress, aging, osmotic stimuli and other physiological or endocrinological manipulations [2,9,22,25,34].…”