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M A Hofman

Publications and source records attributed to M A Hofman.

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The supraoptic and paraventricular nuclei of the human hypothalamus in relation to sex, age and Alzheimer's disease.

Volume and total cell number were determined in the supraoptic (SON) and paraventricular (PVN) nuclei of 14 male and 16 female subjects ranging in age from 10 to 93 years. In addition, 4 male and 6 female subjects suffering from Alzheimer's disease (AD) and ranging in age from 46 to 97 years were studied. Subjects were divided into two age groups, viz., "young" for subjects up to 60 years, and "old" for subjects older than 60. No sex differences in volume and in total cell number were observed in the SON and PVN in either age group. In addition, no significant correlation was found between total cell number in the SON and PVN and brain weight. No significant differences in volume and total cell number were found in either the SON or PVN between young and old control subjects or between AD cases and controls, indicating that these nuclei are spared from degenerative changes in senescence and AD. Determination of neuron numbers in the SON supported this view. In contrast, volume and total cell counts in the suprachiasmatic decreased in senescence and were dramatically reduced in AD. The present results indicate the occurrence of differential patterns of cell loss within the human hypothalamus with aging and in AD, which are proposed to be related to functional differences between the hypothalamic nuclei.

Adolescent↗

From here to eternity: brain aging in an evolutionary perspective.

There is plenty of evidence to show that a high metabolic rate slowly destabilizes the optimal differentiated state of cells as a result of nonenzymatic processes. Because of the continuing high energy demands of the brain in homeothermic organisms, an evolutionary expansion of this organ has to go with the development of maintenance systems which effectively counteract these degenerative processes. Thus the nerve cells in more encephalized and longer-lived species are probably inherently more stable in maintaining their cellular and molecular integrity in the presence of destabilizing insults than do low encephalized species with short life spans.

Aging↗

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.

Adolescent↗

VIP neurons in the human SCN in relation to sex, age, and Alzheimer's disease.

The brains of 46 control subjects and 21 Alzheimer's disease (AD) patients were studied to determine whether there are age-related or AD-related changes in the vasoactive intestinal polypeptide (VIP) neuron population of the human suprachiasmatic nucleus (SCN). The number of VIP expressing neurons in the SCN of females, ranging in age from 10-91 years, did not change during normal aging. In males, however, the number of VIP neurons in the SCN was highest in the young subjects (10-40 years of age), after which, a dramatic decrease occurred in middle-aged subjects. This resulted in an age-dependent sex difference in the VIP cell population of the SCN: young males had twice as many VIP expressing SCN neurons as young females, whereas in the middle-aged groups, the females had twice as many VIP SCN neurons as the males. A significant decrease in the number of VIP expressing neurons in the SCN was found in female presenile AD patients, i.e., those younger than 65 years.

Adolescent↗

Influence of aging on the seasonal rhythm of the vasopressin-expressing neurons in the human suprachiasmatic nucleus.

The mammalian suprachiasmatic nucleus (SCN) is considered to be a major component of the biological clock implicated in the temporal organization of a variety of physiological, endocrine, and behavioral processes. There is now a great deal of evidence indicating that many of these rhythms are progressively disturbed during senescence. The present study was aimed at investigating the influence of aging on the seasonal rhythm of the vasopressin (VP)-expressing neurons in the human SCN. To that end, brains obtained at autopsy of 48 human 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 annual oscillation in young but not in elderly people. Whereas in young subjects low VP-immunoreactive neuron numbers were found during the summer (May-July) and peak values in autumn (September-November), the SCN of elderly people showed a disrupted annual cycle with a reduced amplitude. These data suggest that the biosynthesis of vasopressin in the human SCN exhibits a seasonal rhythm that becomes disturbed later in life.

Adolescent↗

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.

Adolescent↗

Lifespan changes in the human hypothalamus.

The various cell groups in the human hypothalamus show different patterns of aging, which are the basis for changes in biological rhythms, hormone production, autonomic functions, and behavior. The suprachiasmatic nucleus (SCN), the clock of the brain, exhibits circadian and seasonal rhythms in vasopressin synthesis that are disrupted later in life. Furthermore, the age-related sexual differences in the number of vasoactive intestinal polypeptide neurons in this nucleus reinforces the idea that the SCN is not only involved in the timing of circadian rhythms but also in the temporal organization of reproductive functions. The sexually dimorphic nucleus of the preoptic are (SDN-POA), or intermediate nucleus, is twice as large in men as in women, a difference that arises between the ages of two to four years and puberty. During aging a dramatic, sex-dependent decrease in cell number occurs, leading to values which are only 10-15% of the cell number found in early childhood. The vasopressin and oxytocin producing cells in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) are examples of neuron populations that seem to stay perfectly intact in old age. Parvocellular corticotropin-releasing hormone-containing neurons are found throughout the PVN and are even activated in the course of aging, as indicated by their increase in number and by their coexpression with vasopressin. Part of the arcuate nucleus of the hypothalamus (ARH), or tubero-infundibular nucleus, contains hypertrophic neurons in postmenopausal women. These hypertrophied neurons contain neurokinin-B, substance P, and estrogen receptors and probably act on LHRH neurons as interneurons. The tuberal lateral nucleus (NTL), involved in feeding behavior and energy metabolism, does not show any neuronal loss in senescence. These findings indicate that each cell group of the human hypothalamus has its own sex-specific pattern of aging. In fact, some hypothalamic nuclei show a dramatic functional decline with aging, whereas others seem to become more active later in life.

Arcuate Nucleus of Hypothalamus↗

Metachronanalysis of circannual and circasemiannual characteristics of human suprachiasmatic vasopressin-containing neurons.

We here test for and detect anticipated about-yearly (circannual) changes in the volume and number of vasopressin-containing neurons in the human suprachiasmatic nucleus. We then resolve inferential statistical parameters quantifying the extent and timing (the amplitude and acrophase) of the circannual rhythm previously missed by data inspection and classical biometry. We parametrize about-half-yearly changes previously validated by non-parametric statistical tests. New dynamic circannual and circasemiannual endpoints thus become available for basic investigation and the assessment of disease risk elevation and/or chronoprotopathology. It was earlier demonstrated that the circannual rhythms of prolactin and TSH are prominent classifiers of individuals at high versus low familial and other risk for developing breast or prostate cancer. Any neurocrine or neural mechanisms contributing to this classification are now amenable to study, on a population basis, with the dynamic hypothalamic rhythm characteristics yielded by this metachronanalysis.

Cell Count↗