The AVP and OXT neurons were activated in the PVN in patients with major depression or bipolar disorder. This activation may be associated with activation of the hypothalamic-pituitary-adrenal axis in these patients, since both AVP and OXT are known to potentiate the effects of corticotropin-releasing hormone. Because of their central effects, activation of AVP and OXT neurons may also be related to symptoms of major depression or bipolar disorder.

Animal experiments have shown that the parvocellular oxytocin (OXT) neurons of the hypothalamic paraventricular nucleus (PVN) inhibit food intake. In the present study, the PVN and its OXT neurons have been investigated in an extreme human eating disorder, i.e. the Prader-Willi syndrome (PWS). PWS patients are characterized by gross obesity, insatiable hunger, hypotonia, hypogonadism, and mental retardation. The PVN of 5 PWS patients (2 males and 3 females), varying in age between 22-64 yr, and 27 controls (14 males and 13 females) without any primary neurological or psychiatric diseases was morphometrically investigated after conventional staining with thionine and immunocytochemical staining for OXT and vasopressin (AVP). The thionine-stained volume of the PVN was 28% smaller in PWS patients (P = 0.028), and the total cell number was 38% lower (P = 0.009). The immunoreactivity for OXT and AVP was decreased in PWS patients, although the variability within the groups was high. A strong and highly significant decrease (42%; P = 0.016) was found in the number of OXT-expressing neurons of the PWS patients. The volume of the PVN-containing OXT-expressing neurons decreased by 54% (P = 0.028) in PWS. The number of AVP-expressing neurons in the PVN did not change significantly. The OXT neurons of the PVN seem to be good candidates for playing a physiological role in ingestive behavior as "satiety neurons" in the human hypothalamus.

The human hypothalamus is involved in a wide range of functions in the developing, adult and aging subject and is responsible for a large number of symptoms of neuroendocrine, neurological and psychiatric diseases. In the present review some prominent hypothalamic nuclei are discussed in relation to normal development, sexual differentiation, aging and a number of neuropathological conditions. The suprachiasmatic nucleus, the clock of the brain, shows seasonal and circadian variations in its vasopressin neurons. During normal aging, but even more so in Alzheimer's disease, the number of these neurons decreases. In homosexual men this nucleus is larger than in heterosexual men. The difference between the sexually dimorphic nuclei of men and women arises between the ages of 2-4 to puberty. In adult men this nucleus is twice as large as in adult women. In the process of aging, a sex-dependent decrease in cell number occurs. The vasopressin and oxytocin cells of the supraoptic and paraventricular nucleus are present in adult numbers as early as mid-gestation. Lower oxytocin neuron numbers are found in Prader-Willi syndrome, AIDS and Parkinson's disease. Familial hypothalamic diabetes insipidus is based upon a point mutation in the vasopressin-neurophysin-glycopeptide gene. Parvicellular corticotropin-releasing hormone-containing neurons in the paraventricular nucleus increase in number and are activated during the course of aging. In post-menopausal women, the infundibular or arcuate nucleus contains hypertrophic neurons containing oestrogen receptors. These neurons may be involved in the initiation of menopausal flushes. The nucleus tuberalis lateralis may be involved in feeding behaviour and metabolism. In Huntington's disease the majority of its neurons is lost; in Alzheimer's disease it shows very strong cytoskeletal alterations. Tuberomammillary nucleus neurons contain, e.g., histamine or galanine, and project to the cortex. Strong cytoskeletal changes, as well as plaques and tangles are found in this nucleus in Alzheimer's disease. The various hypothalamic nuclei are probably involved in many functions and symptoms of which only a minority has been revealed.

Total cell numbers in the paraventricular nucleus (PVN) were previously shown to remain unaltered with aging and in AD. The aim of the present study was to determine the aging pattern of the oxytocin (OXT) cell population in the PVN. For this purpose, the number of immunocytochemically identified oxytocin cells was determined in the PVN of the human hypothalamus in 20 control subjects ranging in age from 15 to 90 years and in 10 Alzheimer's disease (AD) patients aged 46 to 97 years. The results show that the number of OXT cells in the PVN is similar in males and females and remains unaltered in senescence and AD. It is concluded that the remarkable stability of the PVN in these conditions also applies for the subpopulation of OXT cells in this nucleus and that reports in the literature on diminished OXT secretion in AD do not seem to be based on a decrease in the number of OXT expressing neurons from the PVN.

We determined the number of immunocytochemically identified oxytocin (OXT) and vasopressin (AVP) neurons in the paraventricular nucleus (PVN) of the human hypothalamus of six Parkinson's disease (PD) patients ranging from 59 to 83 years of age. Six subjects without a primary neurologic or psychiatric disease, ranging from 69 to 88 years of age, served as controls. The OXT-immunoreactive cell number in the PVN of the PD patients was 22% lower than that of the control subjects. Although Lewy bodies were present in the nucleus basalis of Meynert, there were no Lewy bodies in the PVN of these patients. Doubt is raised about the presumed direct relationship between the presence of Lewy bodies and neuronal degeneration in PD. The AVP-immunoreactive cell number in the PD patients showed a similar decreasing trend, but the 18% reduction failed to reach statistical significance. The presence of tyrosine hydroxylase-positive neurons in the PVN was not affected in PD patients, supporting the notion that dopaminergic neurons of the mesencephalon, but not of the hypothalamus, are affected in PD. The decreased number of OXT-containing neurons in the PVN suggests that dopamine may be important for the function of these neurons and may provide a neural basis for some autonomic and endocrine disturbances in PD.