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E Fliers

Publications and source records attributed to E Fliers.

At least 55 records · Page 3Linked to original sources

Distribution of thyrotropin-releasing hormone (TRH)-containing cells and fibers in the human hypothalamus.

In the present study, we describe for the first time the distribution of thyrotropin-releasing hormone (TRH)-containing cells and fibers in the human hypothalamus using brain material obtained with a short postmortem delay. Following fixation in paraformaldehyde, glutaraldehyde and picric acid, excellent staining was obtained with two different TRH antisera. Many TRH-containing neurons were present in the paraventricular nucleus (PVN), especially in the dorsocaudal part of this nucleus. They were mostly parvicellular, but a few magnocellular TRH-positive neurons were observed as well. The PVN also contained a dense network of TRH fibers. The supraoptic nucleus (SON) did not show any TRH immunoreactivity, excluding the possibility of cross-reactivity of the antiserum with neurohypophysial hormones or their precursors. In addition, TRH cells were found in the suprachiasmatic nucleus (SCN), which is the circadian clock of the brain, in the sexually dimorphic nucleus (SDN) and dorsomedially of the SON. We observed small number of TRH cells throughout the hypothalamic gray in all subjects studied. A high density of TRH-containing fibers was seen not only in the median eminence but also in other hypothalamic areas, e.g., in the ventromedial nucleus (VM) and in the perifornical area. The results generally agree with earlier data in the rat, with the exception of the absence of TRH cells in the SON. The large number of sites of TRH-containing fiber terminations on neurons suggests important physiological functions of this neuropeptide as a neurotransmitter or neuromodulator in the human brain, in addition to its role as a neurohormone in pituitary secretion of thyroid-stimulating hormone (TSH).

Aged↗

Testosterone supplementation restores vasopressin innervation in the senescent rat brain.

The vasopressin (AVP) innervation in the male rat brain is decreased in senescence. This decrease is particularly pronounced in brain regions where AVP fiber density is dependent on plasma levels of sex steroids. Since plasma testosterone levels decrease progressively with age in the rat, the possibility of restoring central AVP innervation by peripheral testosterone supplementation was investigated by giving senescent (33 months) Brown-Norway rats subcutaneous implants of either empty or testosterone-filled silastic tubes for the period of 1 month. Plasma testosterone levels of testosterone-treated animals were restored to values which did not differ from those of young animals. The results show that the age-related decline in AVP fiber density can indeed be reversed by testosterone supplementation. In contrast, oxytocin innervation, which was previously shown not to be testosterone-dependent, was not restored. These results show for the first time restoration of a specific innervation pattern in the senescent rat brain mediated by peripheral hormones and indicate that a considerable plasticity is retained in the aging central nervous system.

Aging↗

Vasopressin and oxytocin excretion in the Brown-Norway rat in relation to aging, water metabolism and testosterone.

There is considerable disagreement in the literature on changes in the hypothalamo-neurohypophyseal system (HNS) with aging: some reports support HNS degeneration, whereas others claim an activation of this system in senescence. In order to study age-related changes in vasopressin (VP) and oxytocin (OT) excretion in relation to water metabolism, six young (4 months) and 12 aged (34 months) male Brown-Norway rats were placed in metabolism cages. Since plasma testosterone levels have been reported to affect HNS activity and to decline progressively with age, half of the aged animals were given subcutaneous testosterone implants. Urine volume and water intake were significantly increased in aged animals, while urine osmolality was significantly reduced. These changes could not be attributed to diminished VP secretion, since 24-h urinary excretion of this peptide was elevated in the aged animals. In addition, 24-h OT excretion was elevated in the aged animals, indicating an overall activation of the HNS in senescence. VP excretion was significantly correlated with urine osmolality, urine volume and urinary VP concentration. No significant differences were observed between testosterone- and sham-implanted aged rats. It is concluded that the moderate polyuria/polydipsia in the senescent Brown-Norway rat is probably due to renal changes and is accompanied by a compensatory rise in both VP and OT secretion. Testosterone does not affect these changes.

Aging↗

Morphometric analysis of the suprachiasmatic and paraventricular nuclei in the human brain: sex differences and age-dependent changes.

The size, shape and cellular morphology of the suprachiasmatic (SCN) and paraventricular nuclei (PVN) in the human hypothalamus were examined in relation to sex and age. In both nuclear regions the following parameters were determined: length of the rostrocaudal axis, maximum cross sectional area, volume, numerical cell density, total number of cells and the diameter of cell nuclei. No sexual difference was observed in any of these parameters, either in the SCN or in the PVN, with the exception of a sexual dimorphism in the shape of the SCN. In contrast to the absolute measurements, sexual differences were found in the internal structural organisation of these hypothalamic nuclei using multivariate regression analysis. Of the parameters measured only the volume of the SCN in females showed a continuous decrease with ageing, whereas the changes in the other variables were not consistent. Regression analysis revealed that this decrease in SCN volume is mainly caused by cell loss rather than by a reduction in cell size. Finally, a comparison of the volumetric measurements of the human SCN and PVN with those of the rat showed that the human SCN is reduced in size relative to other hypothalamic nuclei. Possible consequences of this phenomenon for the functional significance of the SCN in man are discussed.

Adolescent↗

Changes in vasopressin and testosterone in the senescent brown-Norway (BN/BiRij) rat.

Although earlier reports in the literature suggested degenerative changes in the senescent hypothalamo-neurohypophyseal system (HNS), recent investigation showed hyperactivity of this system in the old Wistar (WAG/Rij) rat. In the brain, changes were found in those sites of extrahypothalamic vasopressin (VP) fiber termination that are testosterone-dependent. In the present study, further evaluation of these changes was performed in male Brown-Norway (BN/BiRij) rats. Immunocytochemical staining of VP binding sites in renal tubuli of the senescent, 33-month-old rats was occasional, and could only slightly be enhanced up to weak staining by in vitro preincubation with the peptide, in contrast to the intense staining observed in young, 3-month-old rats. Although VP plasma levels of young and old rats did not differ significantly and no change in either urine or plasma osmolality was observed, urinary VP concentration and 24-hour urinary VP excretion were significantly increased in senescent rats. The activation of the hypothalamo-neurohypophyseal system (HNS) in the senescent rat seems thus to compensate for a decreased responsiveness to VP in the aged kidney. Testicular weight in the senescent animals declined by 40% and a highly significant decrease of 80-90% was observed in total and free testosterone plasma levels. Consequently, changes in peripheral organs in senescent rats may well underly the changes observed in the brain of these animals.

Aging↗

Extrahypothalamic vasopressin and oxytocin in the human brain; presence of vasopressin cells in the bed nucleus of the stria terminalis.

In the present study, the distribution of extrahypothalamic vasopressin (VP) and oxytocin (OXT) in the human brain was investigated by means of immunocytochemistry. In the septum verum, few VP fibers were found in the nucleus septalis lateralis and medialis (NSL and NSM), and in the bed nucleus of the anterior commissure. Very few VP and OXT fibers were present in the amygdala and in the hippocampus, mainly around the rostral tip of the lateral ventricle on the level of the pes hippocampi. The locus coeruleus (LC) contained dense networks of VP fibers and, although to a lesser extent, OXT fibers over its entire rostrocaudal extension. VP-immunoreactive neurons were present in the bed nucleus of the stria terminalis in a number of subjects, while no OXT cells were found in this structure. Thus, the VP innervation of limbic structures in the human brain, in particular of the NSL, was found to be clearly less pronounced than in the rat brain. The VP innervation of the LC, by contrast, was denser in the human brain than in the rat brain. No sex differences were found in the VP innervation of the human brain. These findings stress the need for caution in extrapolation of data concerning peptidergic innervation of the rat brain towards the human brain.

Adolescent↗

[Increased vasopressin production in senescence and dementia].

Vasopressin (VP) is involved as a neurotransmitter in a number of central functions that are frequently disturbed during aging and dementia. Therefore, this peptide has been used in clinical trials as a 'substitution therapy' for the degenerating peptidergic neurons, aimed at improving cognitive functions in aged and demented individuals with unequivocal results. In order to investigate whether the VP systems indeed show the claimed degenerative changes during aging and dementia, we focused in the first place on the Supra Optic Nucleus (SON) and Para Ventricular Nucleus (PVN). VP cells were identified by means of immunocytochemistry in a series of 32 formalin-fixed human hypothalami, including 4 patients with senile dementia of the Alzheimer type (SDAT). In the SON and PVN, VP cell and nucleolar size was determined by means of a digitizer device, as parameter for peptide synthesizing activity. VP cell size and nucleolar size increased beyond 80 years of age, both in the PVN and in the SON. In SDAT patients these measures fell within the range for their age group. Instead of degenerative changes, these results show an activation of the vasopressinergic system in senescence and in SDAT patients, similar to earlier observations in the aged rat and in accordance with a rise in human neurophysin and VP levels reported recently. The cause for these changes might be in the kidney. Immunocytochemical staining of VP binding sites in the renal tubuli was strongly diminished in kidneys of old (25 and 34 months) as compared to young (3 and 5 months) Wistar and Brown-Norway rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Changes with aging in the vasopressin and oxytocin innervation of the rat brain.

The effect of aging on the vasopressin (AVP) and oxytocin (OXT) innervation of the brain was studied by means of immunocytochemistry, comparing the major innervated areas in 5-month-old and 34-month-old male Brown-Norway rats. A marked decrease of AVP fiber density was found in the old rats as compared with the young animals in the vertical limb of the diagonal band, the basal nucleus of Meynert, the lateral habenular nucleus, the medial amygdaloid nucleus, the substantia nigra, the ventral hippocampus, the central gray, the locus coeruleus and in the ambiguus nucleus. The AVP innervation of the lateral septum and the dorsomedial hypothalamic nucleus was moderately, although not significantly reduced. No age difference in AVP innervation was found in the paraventricular thalamic nucleus or in the nucleus of the solitary tract. OXT fiber density did not differ between young and old animals in the locus coeruleus, the nucleus of the solitary tract and the ambiguus nucleus. Thus, the aging process appears to affect AVP cells in a differential, rather than in a general way. Changes were found to be more pronounced in those areas where the AVP innervation is dependent upon circulating androgens.

Aging↗

The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia.

The suprachiasmatic nucleus (SCN) is considered to be the endogenous clock of the brain, essential for the ovulation cycle and the temporal organization of sleep-wake patterns, among other things. Immunocytochemical staining with anti-vasopressin as a marker permitted a morphometric study of this nucleus in the human brain, which revealed that the shape of the SCN is sexually dimorphic. The shape of the SCN was elongated in women and more spherical in men. In both sexes a decrease in SCN volume and cell number was observed in senescence (80-100 years). The latter change was especially pronounced in patients with senile dementia of the Alzheimer type (SDAT). This suggests the presence of a structural defect in the SCN which underlies the general disturbance of biological rhythms in senescence and SDAT.

Adolescent↗

The vasopressin and oxytocin neurons in the human supraoptic and paraventricular nucleus; changes with aging and in senile dementia.

The neuropeptides vasopressin (AVP) and oxytocin (OXT) are supposed to be involved not only in peripheral functions (e.g. diuresis, labour and lactation) but also in central processes that are frequently disturbed during aging and senile dementia (e.g. fluid and electrolyte homeostasis and cognitive functions). A concomitant decrease in activity of the hypothalamo-neurohypophyseal system (HNS) with aging has been postulated in the literature, but has not yet been established. In order to investigate possible age-related changes in the human HNS, immunocytochemically identified AVP and OXT neurons in the paraventricular and supraoptic nucleus (PVN and SON) were analysed morphometrically in subjects from 10 to 93 years of age, including patients with senile dementia of the Alzheimer type (SDAT). Cell size was used as a parameter for peptide production. Mean profile area of OXT cells did not show any significant changes with increasing age. Mean profile area of AVP cells, however, showed an initial decrease up to the sixth decade of life, after which a gradual increase was observed. Size of AVP and OXT cell nuclei did not change significantly with aging. Observations in brains from patients with SDAT were within the range for their age group. The present results do not support degeneration or diminished function of the HNS in senescence or SDAT, as generally presumed in the literature, but suggest an activation of AVP cells after 80 years of age. The activation of AVP cells in senescence is in accordance with previous findings in the aged Wistar rat.

Adolescent↗

A sexually dimorphic nucleus in the human brain.

A sexually dimorphic cell group is described in the preoptic area of the human hypothalamus. Morphometric analysis revealed that the volume of this nucleus is 2.5 +/- 0.6 times (mean +/- standard error of the mean) as large in men as in women, and contains 2.2 +/- 0.5 times as many cells. Between the ages of 10 and 93 years, the nucleus decreases greatly in volume and in cell number. Although no function has yet been established for this nucleus, it is located within an area that is essential for gonadotropin release and sexual behavior in other mammals.

Adolescent↗

Activation of vasopressin neurons in the human supraoptic and paraventricular nucleus in senescence and senile dementia.

A recent study has shown that vasopressin (AVP) cells in the human supraoptic (SON) and paraventricular (PVN) nuclei increase in size after 60 years of age, suggesting that AVP production is increased in senescence. In the present study, the same brain material was used for the determination of nucleolar size in immunocytochemically identified AVP and oxytocin (OXT) neurons as an additional parameter for peptide production. A strong correlation was found between nucleolar size and cell size, both in AVP and OXT neurons. Nucleolar size of AVP but not of OXT neurons increased significantly in senescence. Observations in brains from patients with senile dementia of the Alzheimer type (SDAT) were commensurate with their ages. These results strongly support the hypothesis that AVP neurons in the SON and PVN are activated in old age.

Adolescent↗