FSH to estradiol ratio can be used as screening method for mild cognitive impairment in postmenopausal women.

OBJECTIVE: To determine the role of anthropometric measurement, menopausal symptoms and biochemical marker changes as screening methods for mild cognitive impairment (MCI) in postmenopausal women Methods: A cross-sectional study included 282 postmenopausal women in Jakarta, further classified into two groups, with and without MCI. Some related variables such as age, body mass index (BMI), duration of menopause, vasomotor symptoms, hormone levels such as follicle stimulating hormone (FSH), luteinizing hormone, leptin, estradiol, and cognitive status, were assessed and analyzed. RESULTS: The FSH levels significantly correlated with MCI incidence (p = 0.018), along with the ratio of FSH/estradiol levels (p = 0.029) and ratio of FSH/soluble leptin receptor (p = 0.011), while other variables did not. By multivariate analysis, the ratio of FSH/estradiol was known as the most significant factor with a probability of having MCI in menopausal women of 1.15. Using the ROC curve, the threshold of the ratio FSH/estradiol to predict MCI was 1.94, with sensitivity 66.5% and specificity 46.8%. CONCLUSIONS: The ratio of FSH to estradiol (>1.94) can be used as a screening method for the occurrence of MCI in postmenopausal women.

Depression in Parkinson's disease is not accompanied by more corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus.

BACKGROUND: Depression is frequently encountered in Parkinson's disease (PD). In addition, more than half of the PD patients have a disturbed dexamethasone suppression test, which is associated with increased activity of corticotropin-releasing hormone (CRH) neurons. We recently found an increase in CRH neuron number, CRH-messenger RNA, and vasopressin colocalization in CRH neurons in the paraventricular nucleus (PVN) of depressed patients, which may be involved in the pathogenesis of depression. METHODS: The number of neurons expressing CRH was determined in the PVN of 6 depressed PD patients with a high score (> or = 13) on the Hamilton Depression Rating Scale, 6 nondepressed PD patients, and 6 controls. RESULTS: The three groups did not differ in the number of neurons expressing CRH. CONCLUSIONS: We hypothesize that activation of CRH neurons in the PVN, as we recently observed in idiopathic depression, does not play an essential role in depression in PD.

Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression.

BACKGROUND: Cerebrospinal fluid levels of arginine vasopressin (AVP) and oxytocin (OXT) have been found to change in mood disorders. In the present study, the numbers of AVP-immunoreactive (IR) and OXT-IR neurons were determined in the paraventricular nucleus (PVN) of the human hypothalamus. METHODS: Postmortem brain tissue was fixed in formalin, embedded in paraffin, and stained for AVP and OXT using immunocytochemical techniques. The number of IR neurons in the PVN was estimated by morphometry in eight depressed patients ranging in age from 21 to 85 years and eight age-matched controls ranging in age from 23 to 88 years. RESULTS: The numbers of AVP-IR and OXT-IR neurons in the PVN of patients with mood disorder were increased by 56% and 23%, respectively. No differences were found in AVP-IR or OXT-IR cell numbers between three patients with major depression and three patients with bipolar depression. The numbers of AVP-IR and OXT-IR neurons in two patients with depression not otherwise specified were within the same range as in the six other patients with a mood disorder. CONCLUSIONS: 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.

Increased number of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of patients with multiple sclerosis.

Observations in experimental allergic encephalomyelitis (EAE), a model for multiple sclerosis (MS), have indicated that a low activity of the hypothalamo-pituitary-adrenal (HPA) system is accompanied by a high susceptibility for EAE in rat strains and that elevated corticosteroid levels are necessary for spontaneous recovery from EAE. The HPA axis activity is regulated by both corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP). Both types of neurons are localized in the paraventricular nucleus (PVN) of the hypothalamus. We determined the number of immunocytochemically identified CRH-immunoreactive (CRH-IR) and AVP-immunoreactive (AVP-IR) neurons in the PVN of the human hypothalamus of 8 MS patients, aged 34-63 years, and 8 age-matched control subjects without any primary neurological or psychiatric disorders, aged 30-59 years. In addition, the number of oxytocin (OXT) immunoreactive (OXT-IR) neurons was determined, since these neurons innervate brain stem nuclei and might thus be related to autonomic disturbances in MS. In MS the staining intensity for AVP was clearly lower and for OXT slightly lower. For CRH, the staining intensity was similar in both groups, and, moreover, in MS patients the number of CRH-IR cells in the PVN was found to be about 2.4 times higher than that in the control group. The number of OXT-IR or AVP-IR cells in the PVN of MS patients was not significantly different from that of the control group. Our results point to an activation of the neuroendocrine HPA axis which may be compatible with the idea that the HPA axis is involved in recovery from MS.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: a study of five cases.

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.

No vasopressin cell loss in the human hypothalamus in aging and Alzheimer's disease.

The total number of immunocytochemically identified vasopressin (AVP) cells was determined morphometrically in the paraventricular (PVN) and dorsolateral part of the supraoptic nucleus (dl-SON) of the human hypothalamus in 30 subjects ranging in age from 15 to 97 years, including 10 Alzheimer's disease (AD) patients. The aim of the present study was to test the hypothesis that the increased activity of AVP neurons reported earlier is accompanied by an absence of cell loss in these nuclei in senescence and AD. The results show that numbers of immunoreactive AVP cells in the PVN and dl-SON do not decline during aging or in AD. During aging, the number of neurons expressing AVP even increased in the PVN of control subjects. The nuclear diameter of the AVP cells in the PVN and dl-SON showed an increase in old AD patients. It is concluded that no cell loss occurs in the AVP cell population in the PVN and dl-SON during aging and in AD, and that AVP expression increases in the PVN during normal aging, but not in AD.

Decreased number of oxytocin-immunoreactive neurons in the paraventricular nucleus of the hypothalamus in Parkinson's disease.

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.

Decreased number of oxytocin neurons in the paraventricular nucleus of the human hypothalamus in AIDS.

The number of immunocytochemically identified vasopressin (AVP) and oxytocin (OXT) neurons was determined morphometrically in the paraventricular nucleus of the hypothalamus of 20 acquired immunodeficiency syndrome (AIDS) patients and 10 controls. The AIDS group consisted of 14 homosexual males (age range 25-62 years), four of whom had a probable HIV-1 associated dementia complex, and six non-demented heterosexuals (four males and two females, age range 21-73 years). Ten males without a primary neurological or psychiatric disease served as a control group. The number of OXT-expressing neurons in the paraventricular nucleus of both groups of AIDS patients was approximately 40% lower than that of the controls. In contrast, the three groups showed no significant differences in the number of AVP-expressing neurons in the paraventricular nucleus. Since there were no significant differences in the number of AVP and OXT cells between the homosexual and heterosexual subjects with AIDS, the morphological difference in the paraventricular nucleus seems to be related to AIDS and not to sexual orientation. No inflammatory changes were found in the paraventricular nucleus area. The selective changes in the OXT neurons of the paraventricular nucleus may be the basis for part of the neuroendocrine, autonomic dysfunction or vegetative symptoms in AIDS.

Annual variations in the vasopressin neuron population of the human suprachiasmatic nucleus.

The mammalian suprachiasmatic nucleus is considered to be the major component of the biological clock, involved in the temporal organization of a wide variety of physiological and behavioral processes. The present study was conducted to investigate whether there are diurnal or annual variations in the morphology of the vasopressin-containing neuron population of the suprachiasmatic nucleus in human beings. To that end, the brains of 48 human subjects were investigated. A marked annual variation was observed in the volume and vasopressin cell number of the human suprachiasmatic nucleus: the volume of the vasopressin cell population was, on average, 2.5 times larger in October-November than in May-June and contained 2.7 times as many vasopressin-immunoreactive neurons. In general, the annual cycle of the human suprachiasmatic nucleus showed a non-sinusoidal pattern with a maximum in early autumn, a lower plateau in winter and a deep trough in late spring and early summer. In contrast, no such seasonal variations could be detected in suprachiasmatic nucleus vasopressin numerical cell density or cell-nuclear diameter. The number of vasopressin-immunoreactive neurons in the paraventricular nucleus of the hypothalamus, on the other hand, did not show any significant periodic changes over the year, indicating the specificity of the suprachiasmatic nucleus rhythm. In contrast with the annual cycle of the suprachiasmatic nucleus, no significant diurnal variations were observed in any of these parameters. In conclusion, the findings indicate that photoperiod may be considered a potential environmental factor controlling the activity of the vasopressin system of the human suprachiasmatic nucleus.

Functional neuroanatomy and neuropathology of 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.

Oxytocin cell number in the human paraventricular nucleus remains constant with aging and in Alzheimer's disease.

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.

Morphometric analysis of the supraoptic nucleus in the human brain.

The supraoptic nucleus (SON) in the human hypothalamus is an elongated, densely packed collection of large neurosecretory cells. The size, shape and cellular morphology of the dorsolateral part of the SON was examined in relation to sex and age in adult subjects. In this region, the following parameters were measured: length of the rostrocaudal axis, maximum cross-sectional area, volume, numerical cell density, total cell number and the mean diameter of the cell nuclei. No sexual differences were observed in any of these parameters with the exception that males have a more elongated SON than females. In contrast to absolute size, sex-linked differences were found in the way the morphometric parameters are interrelated. Of the parameters investigated, only the number of cells in the SON showed significant changes with ageing. A striking increase in the total number of cells, by about 30%, was found between 40 and 65 years of age. A further increase in cell number was observed after the age of 65 years, as a result of which the nucleus contained, on average, 1.4 times as many cells in old subjects (65-90 years) as in young individuals (20-40 years). These findings suggest that a substantial proliferation of glial cells takes place in the human supraoptic nucleus with advancing age. Finally, the morphology of the SON was compared with that of other hypothalamic regions--the suprachiasmatic nucleus (SCN) and the paraventricular nucleus (PVN)--using the same material as that used in previous investigations in this series (Hofman et al. 1988; Hofman & Swaab, 1989).