Abstract
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 hypertrophie 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.
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Airaksinen MS, Paer A, Paljärvi L, Reinikanen K, Riekkinen P, Panula P (1991) Histamine neurons in human hypothalamus: anatomy in normal and Alzheimer diseased brains. Neuroscience 44:465–481
Allen LS, Hines M, Shryne JE, Gorski RA (1989) Sex difference in the bed nucleus of the stria terminalis of the human brain. J Comp Neurol 302:697–706
Bahnsen U, Oosting P, Swaab DF, Nahke P, Richter D, Schmale H (1992) A missense mutation in the vasopressin-neurophysin precursor gene cosegregates with human autosomal dominant neurohypophyseal diabetes insipidus. EMBO J 11:19–23
Barry J (1977) Immunofluorescence study of LRF neurons in man. Cell Tissue Res 181:1–14
Bergeron C, Kovacs K, Ezrin C, Mizzen C (1991) Hereditary diabetes insipidus: an irnmunohistochemical study of the hypothalamus and pítuitary gland. Acta Neuropathol 81:345–348
Borson-Chazot F, Jordan D, Févre-Montange M, Kopp N, Tourniaire J, Rouzioux JM, Veisseire M, Mornex R (1986) TRH and LH-RH distribution in discrete nuclei of the human hypothalamus: evidence for a left predominance of TRH. Brain Res 382:433–436
Braak H, Braak E (1987) The hypothalamus of the human adult: chiasmatic region. Anat Embryol 176:315–330
Braak H, Braak E (1989) Cortical and subcortical argyrophylic grains characterize a disease associated with adult onset dementia. Neuropathol Appl Neurobiol 15:13–26
Braak H, Braak E (1992) Anatomy of the human hypothalamus (chiasmatic and tuberal region) In: Swaab DF, Hofman MA, Mirmiran M, Ravid R, Van Leeuwen FW (eds) The human hypothalamus in health and disease. Progress in brain research, vol 93. Elsevier, Amsterdam, pp 3–16
Braverman LE, Mancini JP, McGoldrick DM (1965) Hereditary idiopathic diabetes insipidus. A case report with autopsy findings. Ann Intern Med 63:503–508
Campbell SS, Kripke DF, Gillin JC, Hrubovcak JC (1988) Exposure to light in healthy elderly subjects and Alzheimer patients. Physiol Behav 42:141–144
Carter LS (1992) Oxytocin & Sexual Behavior. Neurosci Biobehav Rev 16:131–144
Chan-Palay VL, Jentsch B (1992) Galinin tuberomammillary neurons in the hypothalamus in Alzheimer's and Parkinson's disease. In: Swaab DF, Hofman MA, Mirmiran M, Ravid R, Van Leeuwen FW (eds) The human hypothalamus in health and disease. Progress in brain research, vol 93. Elsevier, Amsterdam, pp 263–270
Cohen RA, Albers HE (1991) Disruption of human circadian and cognitive regulation following a discrete hypothalamic lesion: a case study. Neurology 41:726–729
De Jonge FH, Louwerse AL, Ooms MP, Evers P, Endert E, Van de Poll NE (1989) Lesions of the SDN-POA inhibit sexual behaviour of male Wistar rats. Brain Res Bull 23:483–492
Diepen R (1962) Der Hypothalamus. In: W Bargmann (ed) Handbuch der mikroskopischen Anatomie des Menschen IV/7. Springer, Berlin Heidelberg New York, pp 1–181
Dierickx K, Vandesande F (1977) Immunocytochemical localization of the vasopressinergic and the oxytocinergic neurons in the human hypothalamus. Cell Tissue Res 184:15–27
Dörner G (1988) Neuroendocrine response to estrogen and brain differentiation in heterosexuals, homosexuals, and transsexuals. Arch Sexual Behav 17:57–75
Fekete M, Van Ree JM, Niesink RJM, De Wied D (1985) Disruption of circadian rhythms induces retrograde amnesia. Physiol Behav 34:883–887
Fliers E, Swaab DF (1983) Activation of vasopressinergic and oxytocinergic neurons during aging in the Wistar rat. Peptides 4:165–170
Fliers E, De Vries GJ, Swaab DF (1985) Changes with aging in the vasopressin and oxytocin innervation of the rat brain. Brain Res 348:1–8
Fliers E, Guldenaar SEF, Van de Wal N, Swaab DF (1986) Extrahypothalamic vasopressin and oxytocin in the human brain; presence of vasopressin cells in the bed nucleus of the stria terminalis. Brain Res 375:363–367
Frolkis VV, Golovchenko SF, Medved VI, Frolkis RA (1982) Vasopressin and cardiovascular system in aging. Gerontology 28:290–302
Gladue BA, Green R, Helleman RE (1984) Neuroendocrine response to estrogen and sexual orientation. Science 225:1496–1499
Gorski RA, Gordon JH, Shryne JE, Southam AM (1978) Evidence for a morphological sex difference within the medial preoptic area of the rat brain. Brain Res 148:333–346
Goudsmit E, Fliers E, Swaab DF (1988a) Vasopressin and oxytocin excretion in the Brown Norway rat in relation to aging, water metabolism and testosterone. Mech Ageing Dev 44:241–252
Goudsmit E, Fliers E, Swaab DF (1988b) Testosterone supplementation restores vasopressin innervation in the senescent rat brain. Brain Res 473:306–313
Goudsmit E, Hofman MA, Fliers E, Swaab DF (1990) The supraoptic and paraventricular nuclei of the human hypothalamus in relation to sex, age and Alzheimer's disease. Neurobiol Aging 11:529–536
Hinton DR, Sadun AA, Blanks JC, Miller CA (1986) Optic nerve degeneration in Alzheimer's disease. N Engl J Med 315:485–487
His W (1893) Vorschläge zur Einteilung des Gehirns. Arch Anat Entwicklungsgesch (Leipzig) 17:172–179
Hofman MA, Swaab DF (1989) The sexually dimorphic nucleus of the preoptic area in the human brain: a comparative morphometric study. J Anat 164:55–72
Hofman MA, Swaab DF (1992a) The human hypothalamus: comparative morphometry and photoperiodic influences. In: Swaab DF, Hofman MA, Mirmiran M, Ravid R, Van Leeuwen FW (eds) The human hypothalamus in health and disease. Progress in brain research, vol 93. Elsevier, Amsterdam, pp 133–149
Hofman MA, Swaab DF (1992b) Seasonal changes in the suprachiasmatic nucleus of man. Neurosci Lett 139:257–260
Hofman MA, Goudsmit E, Purba JS, Swaab DS (1990) Morphometric analysis of the supraoptic nucleus in the human brain. J Anat 172:259–270
Honnebier MBOM, Swaab DF, Mirmiran M (1989) Diurnal rhythmicity during early human development. In: Reppert SM (ed) Development of circadian rhythmicity and photoperiodism in mammals. Perinatology Press, Ithaca, NY, pp 83–103
Hoogendijk JE, Fliers E, Swaab DF, Verwer RWH (1985) Activation of vasopressin neurons in the human supraoptic and paraventricular nucleus in senescence and senile dementia. J Neurol Sci 69:291–299
Horn E, Lach B, Lapierre Y, Hrdina P (1988) Hypothalamic pathology in the neuroleptic malignant syndrome. Am J Psychiatry 145:617–620
Insel TR (1992) Oxytocin — a neuropeptide for affiliation: evidence from behavioral, receptor autoradiographic, and comparative studies. Psychoneuroendocrinology 17:3–35
Ishii T (1966) Distribution of Alzheimer's neurofibrillary changes in the brain stem and hypothalamus of senile dementia. Acta Neuropathol 6:181–187
Ito M, Mori Y, Oiso Y, Saito H (1991) A single base substitution in the coding region for neurophysin II associated with familial central diabetes insipidus. J Clin Invest 87:725–728
Jacobson CD, Shryne JE, Shapiro F, Gorski RA (1980) Ontogeny of the sexually dimorphic nucleus of the preoptic area. J Comp Neurol 193:541–548
Jones E, Burton H, Saper CB, Swanson LW (1976) Midbrain, diencephalic and cortical relationships of the basal nucleus of Meynert and associated structures in primates. J Comp Neurol 167:385–420
Katz B, Rimmer S, Iragui V, Katzman R (1989) Abnormal pattern electroretinogram in Alzheimer's disease: evidence for retinal ganglion cell degeneration? Ann Neurol 26:221–225
Kopp N, Najimi M, Champier J, Chigr F, Charnay Y, Epelbaum J, Jordan D (1992) Ontogeny of peptides in human hypothalamus in relation to sudden infant death syndrome (SIDS). In: Swaab DF, Hofman MA, Mirmiran M, Ravid R, Van Leeuwen FW (eds) The human hypothalamus in health and disease. Progress in brain research, vol 93. Elsevier, Amsterdam, pp 167–188
Kovacs K, Sheehan HL (1982) Pituitary changes in Kallman's syndrome. A histologic, immunocytologic, ultrastructural, and immunoelectron microscopic study. Fert Steril 37:83–89
Kremer HPH (1992) The hypothalamic lateral tuberal nucleus: normal anatomy and changes in neurological diseases. In: Swaab DF, Hofman MA, Mirmiran M, Ravid R, Van Leeuwen FW (eds) The human hypothalamus in health and disease. Progress in brain research, vol 93. Elsevier, Amsterdam, pp 249–261
Kremer HPH, Roos RAC, Dingjan G, Marani E, Bots GTM (1990) Atrophy of the hypothalamic lateral tuberal nucleus in Huntington's disease. J Neuropathol Exp Neurol 49:371–382
Kremer HPH, Swaab DF, Bots GThAM, Fisser B, Ravid R, Roos RAC (1991) The hypothalamic lateral tuberal nucleus in Alzheimer's disease. Ann Neurol 29:279–284
Le Gros Clark WE (1938) Morphological aspects of the hypothalamus. In: Le Gros Clark WE, Beattie J, Riddoch G, Dott NM (eds) The hypothalamus. Morphological, functional, clinical and surgical aspects. Oliver & Boyd, Edinburgh, pp 1–68
Legros JJ, Gilot P, Schmilz S, Bruwier M, Mantanus H, TimsitBerthier M (1980) Neurohypophyseal peptides and cognitive function: a clinical approach. In: Brambilla F, Racagni G, De Wied D (eds) Progress in psychoneuroendocrinology. Elsevier, Amsterdam, pp 325–337
Matsumoto A, Arai Y (1983) Sex difference in volume of the ventromedial nucleus of the hypothalamus in the rat. Endocrinol Jpn 30:277–280
Mirmiran M, Kok JH (1991) Circadian rhythms in early human development. Early Hum Dev 26:121–128
Mirmiran M, Overdijk J, Witting W, Klop A, Swaab DF (1988) A simple method for recording and analyzing circadian rhythms in man. J Neurosci Methods 25:209–214
Mai JK, Kedziora O, Teckhaus L, Sofroniew MV (1991) Evidence for subdivisions in the human suprachiasmatic nucleus. J Comp Neurol 305:508–525
Moore RY (1992) The organization of the human circadian timing system. In: Swaab DF, Hofman MA, Mirmiran M, Ravid R, Van Leeuwen FW (eds) The human hypothalamus in health and disease. Progress in brain research, vol 93. Elsevier, Amsterdam, pp 99–117
Morrison JH, Benoit R, Magistretti PJ, Bloom FE (1983) Immunohistochemical distribution of pro-somatostatin-related peptides in cerebral cortex. Brain Res 262:344–351
Morton A (1961) A quantitative analysis of the normal neuron population of the hypothalamic magnocellular nuclei in man and of their projections to the neurohypophysis. J Comp Neurol 136:143–158
Murphy MR, Seckl JR, Burton S, Checkley SA, Lightman SL (1987) Changes in oxytocin and vasopressin secretion during sexual activity in men. J Clin Endocrinol Metab 65:738–741
Nagai L, Li CH, Hsieh SM, Kizaki T, Urano Y (1984) Two cases of hereditary diabetes insipidus, with an autopsy finding in one. Acta Endocrinol 105:318–323
Nauta WJH, Haymaker W (1969) Hypothalamic nuclei and fiber connections. In: Haymaker W, Anderson E, Nauta WJH (eds) The hypothalamus. Thomas, Springfield, Ill, pp 136–203
Okawa M, Hishikawa Y, Hozumi S, Hori H (1991) Sleep-wake rhythm disorder and phototherapy in elderly patients with dementia. Biol Psychiatry 1:837–840
Olson BR, Drutarosky MD, Stricker EM, Verbalis JG (1991) Brain oxytocin receptor antagonism blunts the effects of anorexigenic treatments in rats: evidence for central oxytocin inhibition of food intake. Endocrinology 129:785–791
Panayotacopoulou MT, Swaab DF (1993) Development of tyrosine hydroxylase-immunoreactive neurons in the human paraventricular and supraoptic nuclei. Dev Brain Res (in press)
Panula P, Airaksinen MS, Pirvola U, Kotilainen E (1990) Histamine containing neuronal system in human brain. Neuroscience 34:129–132
Prinz PN, Viatliano PP, Vitiello MV, Bokan J, Raskind M, Perskind E, Gerber C (1982) Sleep, EEG and mental function changes in senile dementia of the Alzheimer's type. Neurobiol Aging 3:361–370
Raadsheer FC, Sluiter AA, Ravid R, Tilders FJH, Swaab DF (1993) Localization of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the human hypothalamus; age-dependent colocalization with vasopressin. Brain Res (in press)
Ranee NE (1992) Hormonal influences on morphology and neuropeptide gene expression in the infundibular nucleus of post-menopausal women. In: Swaab DF, Hofman MA, Mirmiran M, Ravid R, Van Leeuwen FW (eds) The human hypothalamus in health and disease. Progress in brain research, vol 93. Elsevier, Amsterdam, pp 221–236
Ravid R, Fliers E, Swaab DF, Zurcher C (1987) Changes in vasopressin and testosterone in the senescent Brown-Norway (BN/BiRij) rat. Gerontology 33:87–98
Reppert SM (1992) Pre-natal development of a hypothalamic biological clock. In: Swaab DF, Hofman MA, Mirmiran M, Ravid R, Van Leeuwen FW (eds) The human hypothalamus in health and disease. Progress in brain research, vol 93. Elsevier, Amsterdam, pp 119–132
Rusak B, Zucker I (1979) Neural regulation of circadian rhythms. Physiol Rev 59:449–526
Sack RL, Lewy AJ, Blood ML, Keith LD, Nakagawa H (1992) Circadian rhythm abnormalities in totally blind people: incidence and clinical significance. J Clin Endocrinol Metab 75:127–134
Sandyk R, Iacono RP, Bamford CR (1987) The hypothalamus in Parkinson's disease. Ital J Neurol Sci 8(3): 227–234
Sanford JRA (1975) Tolerance of debility in elderly dependents by supporters at home: its significance for hospital practice. B M J 3:471–473
Saper CB (1985) Organization of cerebral cortical afferent systems in the rat. II Hypothalamocortical projections. J Comp Neurol 237:21–46
Saper CB (1990) Hypothalamus. In: Paxinos G (ed) The human nervous system. Academic Press, San Diego, pp 389–413
Saper CB, German DC (1987) Hypothalamic pathology in Alzheimer's disease. Neurosci Lett 74:364–370
Schwanzel-Fukuda M, Bick D, Pfaff D (1989) Luteinizing hormone-releasing hormone (LHRH)-expressing cells do not migrate normally in an inherited hypogonadal (Kallmann) syndrome. Mol Brain Res 6:311–326
Schwartz WJ, Bosis NA, Hedley-Whyte ET (1986) A discrete lesion of ventral hypothalamus and optic chiasm that disturbed the daily temperature rhythm. J Neurol 233:1–4
Sheehan HL, Kovacs K (1966) The subventricular nucleus of the human hypothalamus. Brain 89:589–614
Simpson WA, Yates CM, Watts AG, Fink G (1988) Congo red birefringent structures in the hypothalamus in senile dementia of the Alzheimer type. Neuropathol Appl Neurobiol 14:381–393
Spencer S, Saper CB, Joh T, Reis DJ, Goldstein M, Raese JD (1985) Distribution of catecholamine-containing neurons in the normal human hypothalamus. Brain Res 328:73–80
Steinbusch HWM, Mulder AH (1984) Localization and projections of histamine immunoreactive neurons in the central nervous system of the rat. In: Björklund A, Hökfelt T, Kuhar MJ (eds) Handbook of chemical neuroanatomy 3. Elsevier, Amsterdam, pp 126–140
Swaab DF (1991) Brain aging and Alzheimer's disease: “wear and tear” versus “use it or lose it”. Neurobiol Aging 12:317–324
Swaab DF, Fliers E (1985) A sexually dimorphic nucleus in the human brain. Science 228:1112–1115
Swaab DF, Hofman MA (1988) Sexual differentiation of the human hypothalamus: ontogeny of the sexually dimorphic nucleus of the preoptic area. Dev Brain Res 44:314–318
Swaab DF, Hofman MA (1990) An enlarged suprachiasmatic nucleus in homosexual men. Brain Res 537:141–148
Swaab DF, Fliers E, Partiman TS (1985) The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res 342:37–44
Swaab DF, Roozendaal B, Ravid R, Velis DN, Gooren L, Williams RS (1987) Suprachiasmatic nucleus in aging, Alzheimer's disease, transsexuality and Prader-Willi syndrome. In: De Kloet R et al (eds) Neuropeptides and brain function. Progress in brain research, vol 72. Elsevier, Amsterdam, pp 301–310
Swaab DF, Hofman MA, Honnebier MBOM (1990) Development of vasopressin neurons in the human suprachiasmatic nucleus in relation to birth. Dev Brain Res 52:289–293
Swaab DF, Gooren LJG, Hofman MA (1992a) The human hypothalamus in relation to gender and sexual orientation. In: Swaab DF, Hofman MA, Mirmiran M, Ravid R, Van Leeuwen FW (eds) The human hypothalamus in health and disease. Progress in brain research, vol 93. Elsevier, Amsterdam, pp 205–215
Swaab DF, Grundke-Iqbal I, Iqbal K, Kremer HPH, Ravid R, Van de Nes JAP (1992b) Tau and ubiquitin in the human hypothalamus in aging and Alzheimer's disease. Brain Res 590:239–249
Treip CS (1992) The hypothalamus and pituitary gland. In: Hume Adams J, Duchen LW (eds) Greenfield's neuropathology. Arnold, London, pp 1046–1062
Trick GL, Barris MC, Bickler-Bluth M (1989) Abnormal pattern electroretinograms in patients with senile dementia of the Alzheimer type. Ann Neurol 26:226–231
Turkenburg JL, Swaab DF, Endert E, Louwerse AL, Van de Poll NE (1988) Effects of lesions of the sexually dimorphic nucleus on sexual behaviour of testosterone-treated female Wistar rats. Brain Res Bull 21:215–224
Ule G, Walter C (1983) Morphological feedback effect on the nucleoli of the neurons in the nucleus arcuatus (infundibularis) to hypophyseal hypogonadism in juvenile haemochromatosis. Acta Neuropathol 61:81–84
Ule G, Schwechheimer K, Tschahargane C (1983) Morphological feedback effect on neurons of the nucl. arcuatus (sive infundibularis) and nucl. subventricularis hypothalami due to gonadal atrophy. Virchows Arch [Pathol Anst] 400:297–308
Ulfig N, Braak H (1984) Amyloid deposits and neurofibrillary changes in the hypothalamic tuberomammillary nucleus. J Neural Transm (P.D. Sect) 1:143
Van Gool WA, Mirmiran M (1986) Aging and circadian rhythms. In: Swaab DF, Fliers E, Mirmiran M, Van Gool WA, Van Haaren F (eds) Aging of the brain and Alzheimer's disease. Progress in brain research, vol 70. Elsevier, Amsterdam, pp 255–279
Vermeulen A (1990) Androgens and male senescence. In: Nieschlag E, Behre HM (eds) Testosterone. Action, deficiency, substitution. Springer, Berlin Heidelberg New York, pp 629–645
Watanabe T, Taguchi Y, Shiosaka S, Tanaka J, Kubota H, Terano Y, Tohyama M, Wada H (1984) Distribution of the histaminergic neuron system in the central nervous system of rats: a fluorescent immunohistochemical analysis with histidine decarboxylase as a marker. Brain Res 295:13–25
Wierda M, Goudsmit E, Van der Woude PF, Purba JS, Hofman MA, Bogte H, Swaab DF (1991) Oxytocin cell number in the human paraventricular nucleus remains constant with aging and in Alzheimer's disease. Neurobiol Aging 12:511–516
Wisniewski KE, Bobinski M (1991) Hypothalamic abnormalities in Down syndrome. The morphogenesis of Down Syndrome. Wiley-Liss, New York, pp 153–167
Witting W, Kwa IH, Eikelenboom P, Mirmiran M, Swaab DF (1990) Alterations in the circadian rest-activity rhythm in aging and Alzheimer's disease. Biol Psychiatry 27:563–572
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Swaab, D.F., Hofman, M.A., Lucassen, P.J. et al. Functional neuroanatomy and neuropathology of the human hypothalamus. Anat Embryol 187, 317–330 (1993). https://doi.org/10.1007/BF00185889
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DOI: https://doi.org/10.1007/BF00185889