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M A Hofman

Publications and source records attributed to M A Hofman.

At least 55 records · Page 3Linked to original sources
PubMed1993

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.

Adolescent↗
PubMed1993

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.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Diurnal and seasonal rhythms of neuronal activity in the suprachiasmatic nucleus of humans.

The mammalian suprachiasmatic nucleus (SCN) is considered to be a critical component of a neural system implicated in the temporal organization of a wide variety of biological processes. Since the environmental light-dark cycle is the main zeitgeber for many of these rhythms, photic information may have a synchronizing effect on the endogenous clock in the SCN by inducing periodic changes in the activity of certain groups of neurons. The present study was conducted to investigate whether the daily light-dark cycle as well as seasonal variations in photoperiod would affect the vasopressin cell population of the human SCN. To that end, the brains of 30 young human subjects (ranging in age from 6 to 47 years) were investigated. We found that the subdivision of the human SCN that contains vasopressin-producing neurons fluctuated significantly over the 24-hr period. The volume of the vasopressin cell population was, on average, 1.4 times as large during the daytime (1000-1800 hr) as during the nighttime (2200-0600 hr), and contained 1.8 times as many vasopressin-immunoreactive neurons. Peak values in both vasopressin volume and vasopressin cell number were observed in the early morning (0600-1000 hr). In general, the SCN contained fewer vasopressin-immunoreactive neurons during the night than during any other period of the natural light-dark cycle. In addition to the diurnal cycle of the SCN, a marked seasonal rhythm was observed. The volume of the vasopressin cell population was, on average, 2.4 times as large in the autumn as in the summer, and contained 3 times as many vasopressin-immunoreactive neurons. In general, the annual cycle of the human SCN showed a nonsinusoidal pattern with a maximum in early autumn, a lower plateau in winter, and a deep trough in late spring and early summer. In contrast with the periodic fluctuations in the number of vasopressin-immunoreactive neurons in the SCN, no significant diurnal or seasonal variations could be detected in the numerical cell density or cell nuclear diameter of vasopressin neurons. In conclusion, the findings indicate that the synthesizing activity of the vasopressin neurons of the human SCN exhibits a diurnal as well as a seasonal rhythm, and that the temporal organization of these processes becomes disturbed later in life.

Adolescent↗
PubMed1992

Seasonal changes in the suprachiasmatic nucleus of man.

The mammalian suprachiasmatic nucleus (SCN) is considered to be the principal component of the biological clock, generating a wide variety of physiological and behavioral circadian rhythms. In addition to its implication in circadian rhythms, the SCN is also involved in the expression of some seasonal cycles. In the present study we show that the volume of the human SCN and the number of vasopressin-immunoreactive neurons contained within it fluctuate significantly over the year, with values being about twice as high in the autumn as in the summer. In contrast, no seasonal variations could be detected in the paraventricular nucleus (PVN), another major vasopressinergic cell group in the hypothalamus. The present findings suggest that the human SCN is influenced by seasonal variations in photoperiod.

Adolescent↗
PubMed1992

The human hypothalamus: comparative morphometry and photoperiodic influences.

The concept of the hypothalamus as a distinct neurological entity concerned with a variety of regulatory processes dates back to the end of the 19th century. Before 1900 there were only vague intimations of the function of the brain surrounding the third ventricle and these were based primarily on various pathological and assorted clinical observations. Since then a large body of evidence has been derived implicating that the hypothalamus contains the control systems which are critically involved in many physiological, endocrine and behavioral processes. Among these are feeding and drinking, reproduction and the regulation of the sleep-wake cycle and temperature. Although the human hypothalamus accounts for only 4 cm3, or 0.3% of the adult brain volume, it contains the integrative systems critical for all these processes. A comparative morphometric analysis of the hypothalamus among mammals revealed that the volume of this part of the brain is highly correlated with brain size, irrespective of the ecological strategy or evolutionary history of the species considered. It appears that the human hypothalamus has just the size we may expect of such a large-brained mammal, but it is considerably larger than would be predicted from its body size. In mammals the preoptic region of the hypothalamus is implicated in the neural control of endocrine functions and in the temporal organization of a wide spectrum of biological rhythms. In recent years, the pivotal role of two hypothalamic cell groups have been considered in this context: the sexually dimorphic nucleus (SDN-POA) as part of the neural circuitry underlying masculine sexual behavior and reproductive functions and the suprachiasmatic nucleus (SCN) as the principal component of the central clock mechanism. Consistent with its role in the temporal organization of circadian processes, investigations in rodents and non-human primates suggest that the SCN is also involved in the seasonal control of reproductive and metabolic phenomena. Since the environmental light-dark cycle is the main Zeitgeber for circadian and seasonal rhythms in most species, including man, photic information could have substantial effects, not only on the neural activity of the biological clock, but also on its underlying structure. Our observations on the human SCN in relation to photoperiod indeed revealed a marked seasonal variation in the morphology of the human SCN. The volume of the SCN was, on average, twice as large in the autumn as in the summer and contained more than twice as many vasopressin immunoreactive neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Circadian Rhythm↗
PubMed1992

Circadian rhythms and the suprachiasmatic nucleus in perinatal development, aging and Alzheimer's disease.

Circadian rhythms are already present in the fetus. At a certain stage of pre-natal hypothalamic development (around 30 weeks of gestation) the fetus becomes responsive to maternal circadian signals. Moreover, recent studies showed that the fetal biological clock is able to generate circadian rhythms, as exemplified by the rhythms of body temperature and heart rate of pre-term babies in the absence of maternal or environmental entrainment factors. Pre-term babies that are deprived of maternal entrainment and kept under constant environmental conditions (e.g., continuous light) in the neonatal intensive care unit run the risk of developing a biological clock dysfunctioning. However, the fact should be acknowledged that at least in mice the development of the circadian pacemaker (i.e., SCN) does not depend on environmental influences (Davis and Menaker, 1981), although other data suggest that severe disruption of the maternal circadian rhythm indeed abolishes the circadian rhythm of the fetal SCN (Shibata and Moore, 1988). During aging and in particular in AD circadian rhythms are disturbed. These disturbances include phase advance and reduced period and amplitude, as well as an increased intradaily variability and a decreased interdaily stability of the rhythm. Among the factors underlying these changes the loss of SCN neurons seems to play a central role. Other contributory factors may be reduced amount of light, degenerative changes in the visual system and the level of activity and decreased melatonin.

Aging↗
PubMed1992

Gender and sexual orientation in relation to hypothalamic structures.

Animal experiments have provided evidence for the presence of sex differences from the synaptic level up to behaviour. Although sex differences in the human brain may have been presumed implicitly since the days of Aristotle, research on the presence of functional and structural sex differences of the human brain started only relatively recently. The most conspicuous sex difference in the mammalian brain was described by Gorski et al. [1978] in the preoptic area (POA) of the rat hypothalamus. We found that the volume of a putative homologue of this sexually dimorphic nucleus (SDN) in the adult human hypothalamus was more than twice as large in men as in women and contained about twice as many cells. Recently a similar sex difference and volume has been described for the human bed nucleus of the stria terminalis and 'interstitial nuclei of the hypothalamus' (INAH). Sexual differentiation of the hypothalamus was generally believed to take place between 4 and 7 months of gestation. A life span study on the SDN of more than 100 subjects revealed, however, that only after the age of 2-4 years postnatally sexual differentiation becomes manifest by a decrease in volume and cell number in the female SDN. If sexual differentiation of the brain indeed takes place postnatally, not only chemical and hormonal factors may influence this process but also social factors. A prominent theory on the development of sexual orientation is that it develops as a result of an interaction between the developing brain and sex hormones. According to Dörner's hypothesis, male homosexuals have a female differentiation of the hypothalamus. This hypothesis was not supported by our observations on the SDN. Neither the SDN volume nor the cell number in the hypothalamus of homosexual men differed from that of heterosexual men. However, a difference in SCN cell number was observed in relation to sexual orientation. The volume and cell number of the SCN of homosexual men was twice as large as that of a reference group. During development, the SCN volume and cell counts reach peak values around 13-16 months after birth. At this age the SCN contains about the same number of cells as the SCN of adult male homosexuals, whereas in the reference group the cell numbers subsequently decline to the adult value, which is about 35% of the peak value.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

The hypothalamic lateral tuberal nucleus and the characteristics of neuronal loss in Huntington's disease.

Neurons in the hypothalamic lateral tuberal nucleus (NTL) were counted in 16 Huntington's disease (HD) patients and 12 controls. The control range was 47,500-71,700. In the HD cases the number ranged from 2,800 to 40,600. The log-transformed counts of the HD patients correlated closely with age-at-death (r = 0.66, P less than 0.01) and age-at-onset (r = 0.78, P less than 0.001), but not with duration of disease, nor with the severity of the neostriatal changes. Because of its vulnerability to the effects of the HD gene and its simplicity, the NTL seems fit to study the characteristics of neuronal death in HD.

Age Factors↗
PubMed1991

At what age is the developing cerebral cortex of the rat comparable to that of the full-term newborn human baby?

By means of a comparative study of experimental data from the literature we estimated at what age the rat cerebral cortex corresponds to that of the full-term newborn human infant with regard to the degree of maturation. As a result of this study we suggest that the 12-13-day-old rat pup fulfills this criterion. This finding should be of use to scientists who use the rat for studying certain processes assumed to occur in the human cerebral cortex around full-term birth.

Animals↗
PubMed1991

Sexual dimorphism of the human brain: myth and reality.

Many neuroanatomical sex differences have been identified in both animals and humans, which may form the neural bases for sex-specific behavior and reproductive as well as non-reproductive functions. The present essay gives a brief review of the findings on sex differences in the human brain. Our observations on the human hypothalamus revealed that the shape of the suprachiasmatic nucleus (SCN)--a structure involved in the regulation of circadian rhythms and reproductive cycles--is elongated in females and more spherical in males. In addition, an extremely large SCN was observed in the brains of homosexual men who died from AIDS. Both the volume of the SCN and the number of vasopressin neurons were about twice as large as in a male reference group. In contrast to the SCN, in which only shape differences were found in relation to gender, the volume and cell number of the sexually dimorphic nucleus of the preoptic area (SDN-POA) showed a marked sexual dimorphism. The mean volume of the SDN-POA was 2.2 times larger in males than in females and contained about twice as many cells. The function of this sexually dimorphic area in humans is not known, but presumably it is involved in the control of male sexual behavior. The fact that no differences in either volume or cell number were observed between the SDN-POAs of homo- and heterosexual men indicates a selectivity of the SCN in this respect and contradicts the view that male homosexuals have a 'female' hypothalamus.

Brain↗
PubMed1991

The fractal geometry of convoluted brains.

The evolution of the brain in mammals is characterized by an overall size increase and structural reorganization. Consequently, the brain's geometry has changed notably since the late Cretaceous. Here I show that the mammalian brain is a fractal structure, the dimensions of which can be described in mathematical terms. Application of the scaling principle to convoluted brains shows that the cortical surface area, with its fractal dimension of D = 2.70 +/- 0.07, is geometrically similar with the amount of white matter, i.e., with the number and length of the interconnective nerve fibers. The hypothesis is put forward that the potential for brain evolution results from a combination of fractal folding and compartmentalization of neurons into modular circuits. The close correspondence between the form and fractal dimensions of the brain and a geometric model provides further evidence that the macroscopic organization of the brain in mammals is governed by a few simple generative rules and that these internal factors of brain design, bearing no relation to the selective reasons of initial enlargement, may be the primary determinants directing the evolution of the brain.

Animals↗
PubMed1990

An enlarged suprachiasmatic nucleus in homosexual men.

Morphometric analysis of the human hypothalamus revealed that the volume of the suprachiasmatic nucleus (SCN) in homosexual men is 1.7 times as large as that of a reference group of male subjects and contains 2.1 times as many cells. In another hypothalamic nucleus which is located in the immediate vicinity of the SCN, the sexually dimorphic nucleus (SDN), no such differences in either volume or cell number were found. The SDN data indicate the selectivity of the enlarged SCN in homosexual men, but do not support the hypothesis that homosexual men have a 'female hypothalamus'.

AIDS Dementia Complex↗
PubMed1990

Development of vasopressin neurons in the human suprachiasmatic nucleus in relation to birth.

The number of neurons expressing vasopressin (AVP) was determined in the suprachiasmatic nucleus (SCN) of the hypothalamus of 41 human subjects ranging in age from 27 weeks of gestation up to 30 years of age. At term, i.e. at 38-42 weeks of gestation, the fetal SCN is still immature, since it then contains only about 13% of the adult number of AVP-expressing neurons. The period of rapid increase in the number of AVP-staining neurons in the SCN during the first few months postnatally coincides with the appearance of overt diurnal rhythms in the child.

Adolescent↗
PubMed1990

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).

Adolescent↗