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M A Hofman

Publications and source records attributed to M A Hofman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Biological rhythms in the human life cycle and their relationship to functional changes in the suprachiasmatic nucleus.

Biological rhythms play a prominent role in the human life cycle. The endogenous rhythms are entrained by the environment and have an astronomical counterpart which is obvious for daily, monthly, and yearly rhythms, and may possibly also be present in weekly rhythms. Circadian rhythms are present in, e.g. testosterone levels, spontaneous birth, strokes, and death from cardiovascular causes. Circaseptan rhythms are present in, e.g. spontaneous birth, 17-ketosteroid levels, myocardial infarctions, and strokes. The relationship of these rhythms with the suprachiasmatic nucleus (SCN) has not yet been established. Circatrigintan rhythms, such as the menstrual cycle, have so far not been associated with the SCN. Circannual rhythms are present in, e.g. mood, suicides, reproduction, birth weight, sleep and season of birth of psychiatric patients. The human SCN shows strong circadian and circannual fluctuations in the number of neurons expressing vasopressin. The vasopressin and VIP cell population of the SCN develop late, i.e. for a major part postnatally. After the age of 50 the amplitudes of circadian and circannual fluctuations of the vasopressin cell numbers are reduced whereas the number of vasopressin expressing neurons decreases after the age of 80 and do so even more and earlier in Alzheimer's disease. Sex differences are present in the shape of the vasopressin subnucleus of the SCN and in the vasoactive intestinal polypeptide (VIP) cell number. The sex differences in the SCN, the doubling of the number of vasopressin neurons in the SCN of homosexual men, and a variety of animal experimental observations indicate that the SCN is involved in sexual behavior and reproduction. The exact role of the SCN in these processes is subject to current research.

Circadian Rhythm↗
PubMed1995

A sex difference in the human brain and its relation to transsexuality.

Transsexuals have the strong feeling, often from childhood onwards, of having been born the wrong sex. The possible psychogenic or biological aetiology of transsexuality has been the subject of debate for many years. Here we show that the volume of the central subdivision of the bed nucleus of the stria terminals (BSTc), a brain area that is essential for sexual behaviour, is larger in men than in women. A female-sized BSTc was found in male-to-female transsexuals. The size of the BSTc was not influenced by sex hormones in adulthood and was independent of sexual orientation. Our study is the first to show a female brain structure in genetically male transsexuals and supports the hypothesis that gender identity develops as a result of an interaction between the developing brain and sex hormones.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Increased light intensity prevents the age related loss of vasopressin-expressing neurons in the rat suprachiasmatic nucleus.

We investigated whether increased light input can counteract the age-related decrease in vasopressin- (AVP) and vasoactive intestinal polypeptide (VIP)-expressing neurons of the suprachiasmatic nucleus (SCN) by determining the numbers of these neurons in rats of different ages, housed under low or high intensities of light. The significant age-related decrease for AVP was prevented in old animals after high light housing. For VIP, no effects were found.

Aging↗
PubMed1995

Early cytoskeletal changes as shown by Alz-50 are not accompanied by decreased neuronal activity.

The nucleus tuberalis lateralis (NTL) is located in the basolateral part of the hypothalamus and is only present as a well-delineated nucleus in human and higher primates. In Alzheimer's disease (AD), NTL neurons show strong early cytoskeletal alterations, as revealed by the antibody Alz-50, but practically no senile plaques or neurofibrillary tangles. To study whether the activity of NTL neurons decreases when cytoskeletal changes appear, i.e., during aging and in AD, we applied a polyclonal antibody raised against the medial cisternae of the Golgi apparatus (GA). The size of the GA and the cell profile of NTL neurons, two established parameters for neuronal activity, were measured by an image analysis system. No significant change in the size of the profiles of the GA or of the neurons was observed in this nucleus during aging or AD. Earlier studies have shown that there is no decrease in cell number in the NTL in AD. We conclude that in the NTL an early hallmark of AD, i.e., cytoskeletal changes as stained by Alz-50, does not correlate with decreased neuronal activity, as reflected by the size of the GA, nor with a decrease in cell number. In addition, we found that the very early occurring and abundant presence of lipofuscin in NTL neurons does not go together with decreased neuronal activity.

Adult↗
PubMed1995

No changes in the number of vasoactive intestinal polypeptide (VIP)-expressing neurons in the suprachiasmatic nucleus of homosexual men; comparison with vasopressin-expressing neurons.

In an earlier study we found more than twice as many vasopressin (AVP) neurons in the suprachiasmatic nucleus (SCN) of homosexual men as compared to heterosexual men. The present measurements in the same individuals showed that there is no difference in the number of vasoactive intestinal polypeptide (VIP)-expressing neurons in the SCN. The reduced nuclear diameter of both VIP and AVP neurons in the SCN as found in homosexual men points to metabolic alterations in the SCN in relation to sexual orientation.

Adult↗
PubMed1995

Effect of photoperiod on the diurnal melatonin and 5-methoxytryptophol rhythms in the human pineal gland.

The mammalian pineal organ is a major endocrine component of the circadian timing system, primarily concerned with the regulation of photoperiodic responses. The effect of different photoperiods on the diurnal variation in the concentration of melatonin and 5-methoxytryptophol (5-ML) was studied in the pineal glands, obtained at autopsy, of 38 human subjects, and measured by radioimmunoassay. A diurnal rhythm in pineal melatonin was evident only in the long photoperiod (April-September) with melatonin concentrations being 4.2 times higher at night (22.00-10.00 h) than during the day (10.00-22.00 h). In contrast, diurnal variations in the pineal 5-ML content were only observed in the short photoperiod (October-March) with high concentrations during day-time and low concentrations during night-time. In general, night-time concentrations of both melatonin and 5-ML were higher in summer than in winter. These data suggest that the synthesis of indoleamines in the human pineal exhibits a diurnal rhythm which is affected by seasonal changes in day length.

Adolescent↗
PubMed1995

Increased activity of hypothalamic corticotropin-releasing hormone neurons in multiple sclerosis.

Clinical observations and animal studies suggest that the hypothalamo-pituitary-adrenal (HPA) axis plays a role in the susceptibility to and the recovery from multiple sclerosis (MS). Since the HPA-axis is under the control of corticotropin-releasing hormone (CRH) neurons of the hypothalamus, we determined 2 parameters for activation of the CRH neurons in the hypothalamic paraventricular nucleus (PVN) in MS patients. Since the HPA-axis is more activated in MS, we expected an increased activity of CRH neurons. We also expected to see an age-related increase in CRH activity, because of the possible role of the HPA-axis in the age-related decrease in susceptibility to MS. The number of CRH cell profiles and the proportion of CRH neurons co-expressing vasopressin were used as parameters for activity. CRH cell population became more activated both in control and MS patients, from 40 years of age onwards, when the prevalence of MS starts to decrease in the population. The CRH neurons showed a significantly higher level of activation in MS patients than in controls, as appeared from the 3-fold increase in CRH cell number and the 4.5-fold increase in cells co-expressing CRH and vasopressin (AVP).

Adult↗
PubMed1995

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)

Adult↗
PubMed1995

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.

Adult↗
PubMed1995

Brain research, gender and sexual orientation.

Recent brain research has revealed structural differences in the hypothalamus in relation to biological sex and sexual orientation. Differences in size and cell number of various nuclei in the hypothalamus for homosexual versus heterosexual men have recently been reported in two studies. We have found that a cluster of cells in the preoptic area of the human hypothalamus contains about twice as many cells in young adult men as in women. We have called this cluster the sexually dimorphic nucleus (SDN). The magnitude of the difference is the SDN depends on age. In other human research, two other hypothalamic nuclei (interstitial nuclei of the anterior hypothalamus [INAH] 2 and 3) and part of the bed nucleus of the stria terminalis (BST) have been reported to be sexually dimorphic in the human. Sexual differentiation to the human brain takes place much later than originally claimed. At birth the SDN contains only some 20% of the cells found at 2 to 4 years of age. The cell number rapidly increases in boys and girls at the same rate until 2 to 4 years of age. After that age period, a decrease in cell number takes place in girls, but not in boys. This causes the sexual differentiation of the SDN. This postnatal period of hypothalamic differentiation indicates that, in addition to genetic factors, a multitude of environmental and psychosocial factors may have profound influence on the sexual differentiation of the brain. No difference in SDN cell number was observed between homosexual and heterosexual men. This finding refutes Dörner's hypothesis that homosexual males have a "female" hypothalamus. However, in a sample of brains of homosexual men we did find that an area of the hypothalamus called the suprachiasmatic nucleus (SCN) contains twice as many cells as the SCN of a heterosexual group. A recent report by LeVay claims that another nucleus, INAH-3, is more than twice as large in heterosexual as in homosexual men, whereas Allen and Gorski found that the anterior commissure was larger in homosexual men than in heterosexual men or women. Preliminary research on male-to-female transsexuals is also discussed. The functional implications of these findings in determining adult sexual orientation are as yet far from clear.

Adolescent↗
PubMed1995

Sexual differentiation of the human hypothalamus in relation to gender and sexual orientation.

Recently, sex differences in the structures of the human hypothalamus and adjacent brain structures have been observed that seem to be related to gender, to gender problems such as transsexuality, and to sexual orientation, that is, heterosexuality and homosexuality. Although these observations have yet to be confirmed, and their exact functional implications are far from clear, they open up a whole new field of physiological structural-functional relationships in human brain research that has so far focused mainly on such relationships in pathology.

Age Distribution↗
PubMed1994

Alterations in circadian rhythmicity of the vasopressin-producing neurons of the human suprachiasmatic nucleus (SCN) with aging.

The suprachiasmatic nucleus (SCN) of the anterior hypothalamus is implicated in the temporal organization of circadian rhythms in a variety of physiological, endocrine and behavioral processes. There is a great deal of evidence indicating that aging is characterized by a progressive deterioration of circadian timekeeping. The present study was aimed at investigating whether there are age-related changes in circadian rhythmicity of the vasopressin (VP)-producing neurons in the human SCN. To that end brains obtained at autopsy of 39 subjects, ranging in age from 6 to 91 years, were studied. Subjects were divided into two age groups, viz. 'young subjects' (up to 50 years) and 'elderly subjects' (over 50 years). It is shown that the number of VP-immunoreactive neurons in the human SCN exhibits a marked diurnal oscillation in young, but not in elderly, people. Whereas in young subjects low VP-immunoreactive neuron numbers were found during the night period (22:00-06:00 h) and peak values during the early morning (06:00-10:00 h), the SCN of elderly people showed a reduced amplitude and a tendency for a reversed diurnal pattern with high instead of low values during the night. The findings suggest that the VP synthesis of the human SCN exhibits a circadian rhythm that is disrupted later in life.

Adolescent↗
PubMed1994

Development of vasoactive intestinal polypeptide neurons in the human suprachiasmatic nucleus in relation to birth and sex.

The development of vasoactive intestinal polypeptide (VIP) neurons was determined in the human suprachiasmatic nucleus (SCN) of 43 subjects ranging from 27 weeks of gestation to 30 years of age using immunocytochemistry and morphometry. VIP neurons were first observed at 31 weeks of gestation in the ventrolateral part of the SCN. From 3 months postnatally onwards, VIP positive neurons were observed in some subjects in the centromedial part of the SCN. The centromedial type of VIP staining became a constant finding only at 19 years of age, at term the SCN was still very immature. Only in a few subjects some VIP neurons stained in the ventrolateral SCN and their number and nuclear diameter was small. Postnatally the number of VIP neurons increased gradually until around 3 years of age adult values were reached. After the age of 10 a clear sex difference in the number of VIP neurons was found: males having on average twice as many VIP neurons in the SCN as females. The adult VIP cell numbers in the SCN amounted only 35% of those found earlier for vasopressin. The present data do not support a particular role for VIP neurons in those rhythms that are already present in early development, e.g., of the temperature rhythm in prematures of around 30 weeks gestational age. Our observations in this and earlier papers as well as animal studies do suggest though a possible role for VIP neurons in the SCN in sexual dimorphic functions such as reproduction and sexual behavior.

Adolescent↗
PubMed1994

Increased cortisol levels in aging and Alzheimer's disease in postmortem cerebrospinal fluid.

The hypothalamo-pituitary-adrenal (HPA) axis is activated during aging and even more so in dementia. Increased levels of corticosteroids may be neurotoxic. Therefore we have investigated cortisol levels in cerebrospinal fluid (CSF) of Alzheimer patients and controls. Ventricular postmortem CSF was collected from clinically and neuropathologically well-defined Alzheimer patients (n = 26) and control subjects (n = 21). In the group of Alzheimer patients the mean CSF total cortisol level was 83% higher than that in the controls. In presenile Alzheimer patients (< 65 years of age; n = 13) the CSF-cortisol level was 5 times higher than that of presenile controls (n = 7). In contrast, senile Alzheimer patients (n = 13) and controls of over 65 years of age (n = 14) did not show a significant difference in CSF-cortisol levels. The presence or absence of a difference in the cortisol-CSF levels in, respectively, presenile or senile Alzheimer patients as compared to controls was due to the 3.5-fold rise of CSF-cortisol in control subjects over 65 years of age as compared with controls under 65 years of age. The CSF-cortisol levels in presenile and senile Alzheimer patients were similar. No significant correlation was observed in the Alzheimer patients between age of onset of the dementia and CSF cortisol levels or duration of Alzheimer's disease and CSF cortisol levels. The finding that in senile Alzheimer patients cortisol levels were similar to those of unaffected age-matched controls does not seem to support the cortisol neurotoxicity hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

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.

Aged↗
PubMed1993

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.

Aged↗