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Horm Metab Res 2006; 38(6): 382-390
DOI: 10.1055/s-2006-944522
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Effects of Chronic Alcoholic Disease on Magnocellular and Parvocellular Hypothalamic Neurons in Men

E.  V.  Sivukhina1, 2, 6 , A.  A.  Dolzhikov2 , Iu.  E.  Morozov3 , G.  F.  Jirikowski1 , V.  Grinevich4, 5, 7
  • 1Department of Anatomy II, Friedrich Schiller University, Jena, Germany
  • 2Department of Histology and Embryology, Kursk State Medical University, Kursk, Russia
  • 3Medical Expert Bureau of Medical Legal Examination, Moscow Public Health Department, Moscow, Russia
  • 4Department of Histology and Embryology, Paediatric Faculty, Russian State Medical University, Moscow, Russia
  • 5Group of Neuroimmunoendocrinology, Institute of General Pathology and Pathological Physiology, Russian Academy of Medical Sciences, Moscow, Russia
  • 6Current address: Institute of Biosynthesis of Neural Structures, Centre of Molecular Neurobiology, University of Hamburg, Germany
  • 7Current address: Department of Molecular Neurobiology, Max-Planck-Institute for Medical Research, Heidelberg, Germany
Further Information

Publication History

Received 30 November 2005

Accepted after revision 20 February 2006

Publication Date:
06 July 2006 (online)

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Abstract

Although numerous data showing severe morphological impairment of magnocellular and parvocellular hypothalamic neurons due to chronic alcoholic consumption have been gathered from animal experiments, only one study (Harding et al., 1996) was performed on post mortem human brain. This study showed a reduction in the number of vasopressin (VP)-immunoreactive neurons in the supraoptic (SON) and paraventricular (PVN) nuclei, but did not provide any data regarding the effect of chronic alcohol intake on human parvocellular neurons. In order to assess whether the changes observed in the animal model also occur in humans and provide a structural basis for the results of clinical tests, we performed immunohistochemical and morphometric analysis of magnocellular (VP and oxytocin, OT) and parvocellular (corticotropin-releasing hormone, CRH) neurons in post-mortem brains of patients afflicted with chronic alcoholic disease. We analyzed 26-male alcoholics and 22 age-matched controls divided into two age groups - “young” (< 40 yr) and “old” (> 40 yr). Hypothalamic sections were stained for OT, VP, and CRH. The analysis revealed: 1) decrease in VP-immunoreactivity in the SON and PVN as well as OT-immunoreactivity in the SON in alcoholic patients; 2) increase in OT-immunoreactivity in the PVN; 3) increase in CRH-immunoreactivity in parvocellular neurons in the PVN. Furthermore, the proportion of cells containing CRH and VP was increased in alcoholics. These findings indicate that chronic alcohol consumption does indeed impair the morphology of magnocellular neurons. The enhancement of CRH-immunoreactivity and increased co-production of CRH and VP in parvocellular neurons may be due to a decline in glucocorticoid production, implied by the hypoplasic impairment of adrenal cortex we observed in alcoholics during the course of this study.

Key words

Vasopressin - oxytocin - corticotrophin-releasing hormone - human - alcoholic disease

References

  • 1 Madeira M D, Paula-Barbosa M M. Effects of alcohol on the synthesis and expression of hypothalamic peptides.  Brain Res Bull. 1999;  48 3-22
    CrossrefPubMedGoogle Scholar
  • 2 Gulya K, Dave J R, Hoffman P L. Chronic ethanol ingestion decreases vasopressin mRNA in hypothalamic and extrahypothalamic nuclei of mouse brain.  Brain Res. 1991;  557 129-135
    CrossrefPubMedGoogle Scholar
  • 3 Sanna P P, Folsom D P, Barizo M J, Hirsch M D, Melia K R, Maciejewski-Lenoir D, Bloom F E. Chronic ethanol intake decreases vasopressin mRNA content in the rat hypothalamus: a PCR study.  Brain Res Mol Brain Res. 1993;  19 241-245
    CrossrefPubMedGoogle Scholar
  • 4 Madeira M D, Sousa N, Lieberman A R, Paula-Barbosa M M. Effects of chronic alcohol consumption and of dehydration on the supraoptic nucleus of adult male and female rats.  Neuroscience. 1993;  56 657-672
    CrossrefPubMedGoogle Scholar
  • 5 Silva S M, Madeira M D, Ruela C, Paula-Barbosa M M. Prolonged alcohol intake leads to irreversible loss of vasopressin and oxytocin neurons in the paraventricular nucleus of the hypothalamus.  Brain Res. 2002;  925 76-88
    CrossrefPubMedGoogle Scholar
  • 6 Ruela C, Sousa N, Madeira M D, Paula-Barbosa M M. Stereological study of the ultrastructural changes induced by chronic alcohol consumption and rehydration in the supraoptic nucleus of the rat hypothalamus.  J Neurocytol. 1994;  23 410-421
    CrossrefPubMedGoogle Scholar
  • 7 Harding A J, Halliday G M, Ng J LF, Harper C G, Kril J J. Loss of vasopressin-immunoreactive neurons in alcoholics in dose-related and time-dependent.  Neuroscience. 1996;  72 699-708
    CrossrefPubMedGoogle Scholar
  • 8 Collins G B, Brosnihan B, Zuti R A, Messina M, Gupta M K. Neuroendocrine, fluide balance, and thirst response to alcohol in alcoholics.  Alcohol Clin Exp Res. 1992;  16 228-233
    CrossrefPubMedGoogle Scholar
  • 9 Legros J J, Deconinck I, Willems D, Roth B, Pelc I, Brauman J, Verbank M. Increase of neurophysin II serum levels in chronic alcoholic patients: relationship with alcohol consumption and alcoholism blood markers during withdrawal therapy.  J Clin Endocrinol Metab. 1983;  56 871-875
    PubMedGoogle Scholar
  • 10 Marchesi C, Chiodera P, Brusamonti E, Volpi R, Coiro V. Abnormal plasma oxytocin and beta-endorphin levels in alcoholics after short and long term abstinence.  Progr Neuro-Psychopharmacol Biol Psychiat. 1997;  21 797-807
    PubMedGoogle Scholar
  • 11 Haddad J J. Alcoholism and neuro-immune-endocrine interactions: physiochemical aspects.  Bichem Biophys Res Commun. 2004;  323 361-371
    PubMedGoogle Scholar
  • 12 Sillaber I, Henninger M SH. Stress and alcohol drinking.  Ann Med. 2004;  36 596-605
    PubMedGoogle Scholar
  • 13 Aguilera G. Regulation of pituitary ACTH secretion during chronic stress.  Front Neuroendocrinol. 1994;  15 321-350
    CrossrefPubMedGoogle Scholar
  • 14 Grinevich V, Ma X-M, Herman J, Jezova D, Akmayev I, Aguilera G. Effect of repeated lipopolysaccharide administration on tissue cytokine expression and hypothalamic-pituitary-adrenal axis activity in rats.  J Neuroendocrinol. 2001;  13 711-723
    CrossrefPubMedGoogle Scholar
  • 15 Grinevich V, Harbuz M, Ma X-M, Jessop D, Tilders F JH, Lightman S L, Aguilera G. Hypothalamic pituitary adrenal axis and immune responses to endotoxin in rats with chronic adjuvant-induced arthritis.  Exp Neurol. 2002;  178 112-123
    CrossrefPubMedGoogle Scholar
  • 16 Lightman S L, Windle R J, Ma X M, Harbuz M S, Shanks N M, Julian M D, Wood S A, Kershaw Y M, Ingram C D. Hypothalamic-pituitary-adrenal function.  Arch Physiol Biochem. 2002;  110 90-93
    CrossrefPubMedGoogle Scholar
  • 17 Silva S M, Paula-Barbosa M M, Madeira M D. Prolonged alcohol intake leads to reversible depression of corticotropin-releasing hormone and vasopressin immunoreactivity and mRNA levels in the parvocellular neurons of the paraventricular nucleus.  Brain Res. 2002;  954 82-93
    CrossrefPubMedGoogle Scholar
  • 18 Wand G S, Dobs A S. Alterations in the hypothalamic-pituitary-adrenal axis in actively drinking alcoholics.  J Clin Endocrinol Metab. 1991;  72 1290-1295
    PubMedGoogle Scholar
  • 19 Halliday G, Ellis J, Heard R, Caine D, Harper C. Brainsteam serotoninergic neurons in chronic alcoholics with and without the memory impairment Korsakoff’s psychosys.  J Neuropath Exp Neurol. 1993;  52 567-579
    PubMedGoogle Scholar
  • 20 Victor M, Adams R D, Collins G H. The Wernicke-Kosakoff syndrome and related neurological disorders due to alcoholism and malnutrition. Philadelphia; F. A. Devis Company 1989
    Google Scholar
  • 21 Zaborsky L, Heimer L. Combination of tracer techniques, especially HRP and PHA-L, with transmitter identification for correlated light and electron microscopic studies. In: Heimer L, Zaborsy L (eds) Neuroanatomical tract tracing methods 2. New York; Plenum Press 1989: 49-96
    Google Scholar
  • 22 Telleria-Diaz A, Grinevich V V, Jirikowski G F. Colocalization of vasopressin and oxytocin in hypothalamic magnocellular neurons in water-deprived rats.  Neuropeptides. 2001;  3 - 4 162-167
    PubMedGoogle Scholar
  • 23 Jezova D, Skultetyova I, Tokarev D I, Bakos P, Vigas M. Vasopressin and oxytocin in stress.  Ann NY Acad Sci. 1995;  771 192-203
    CrossrefPubMedGoogle Scholar
  • 24 Engelmann M, Landgraf R, Wotjak C T. The hypothalamic-neurohypophyseal system regulates the hypothalamic-pituitary adrenal axis under stress: an old concept revisited.  Front Neuroendocrinol. 2004;  25 132-149
    CrossrefPubMedGoogle Scholar
  • 25 Laguna-Abreu M T, Koenigkam-Santos M, Colleta A M, Elias P C, Moreira A C, Antunes-Rodrigues J, Elias L L, Castro M. Time course of vasopressin and oxytocin secretion after stress in adrenalectomized rats.  Horm Metab Res. 2005;  37 84-88
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Chou C L, DiGiovanni S R, Mejia R, Nielsen S, Knepper M A. Oxytocin as an antidiuretic hormone.  Amer J Physiol. 1995;  269 (1 Pt 2) F70-77, F78 - 85
    PubMedGoogle Scholar
  • 27 Haanwinckel M A, Elias L K, Favaretto A L, Gutkowska J, McCann S M, Antunes-Rodrigues J. Oxytocin mediates atrial natriuretic peptide release and natriuresis after volume expansion in the rat.  Proc Natl Acad Sci USA. 1995;  92 7902-7906
    PubMedGoogle Scholar
  • 28 Kovacs G L, Sarnyai Z, Szabo G. Oxytocin and addiction: a review.  Psychoneuroendocrinology. 1998;  23 945-962
    CrossrefPubMedGoogle Scholar
  • 29 Chu I, Poon R, Valli V, Yagminas A, Bowers W J, Seegal R, Vincent R. Effects of an ethanol-gasoline mixture: results of a 4-week inhalation study in rats.  J Appl Toxicol. 2005;  25 193-199
    CrossrefPubMedGoogle Scholar
  • 30 Jedrzejewska E A. Morphochemical and statistical studies of the adrenal cortex in albino rats with chronic alcoholic intoxication. I. Histologic and morphometric studies.  Ann Univ Mariae Curie Sklodowska. 1984;  39 293-301
    PubMedGoogle Scholar
  • 31 Paukov V C, Erokhin Iu A. Endocrine glands in alcohol drinkers and patients with alcoholism.  Arkh Patol. 2001;  63 21-26
    PubMedGoogle Scholar
  • 32 Silva T P, Silverira G A, Fior-Chadi D R, Chadi G. Effects of ethanol consumption on vasopressin and neuropeptide Y immunoreactivity and mRNA expression in peripheral and central areas related to cardiovascular regulation.  Alcohol. 2004;  32 213-222
    CrossrefPubMedGoogle Scholar
  • 33 Hundt W, Zimmermann U, Poettig M, Spring K, Holsboer F. The combined dexamethasone-suppression/CRH-stimulation test in alcoholics during and after acute withdrawal.  Alcohol Clin Exp Res. 2001;  25 687-691
    CrossrefPubMedGoogle Scholar
  • 34 Von Bardeleben U, Heuser I, Holsboer F. Human CRH stimulation response during acute withdrawal and after medium-term abstention from alcohol abuse.  Psychoneuroendocrinology. 1989;  14 441-449
    CrossrefPubMedGoogle Scholar
  • 35 Zimmermann U, Hundt W, Spring K, Grabner A, Holsboer F. Hypothalamic-pituitary-adrenal system adaptation to detoxification in alcohol-dependent patients is affected by family history of alcoholism.  Biol Psychiatry. 2003;  53 75-84
    PubMedGoogle Scholar
  • 36 Dackis C, Stuckley R, Gold M, Pottash A. Dexametasone suppression testing of depressed alcoholics.  Alcohol Clin Exp Res. 1986;  10 59-60
    PubMedGoogle Scholar
  • 37 Bailly D, Dewailly D, Beuscart R, Couplet G, Dumont P, Racadot A, Fossati P, Parquet P J. Adrenocorticotropin and cortisol responses to ovine corticotropin-releasing factor in alcohol dependence disorder. Preliminary report.  Horm Res. 1989;  31 72-75
    PubMedGoogle Scholar
  • 38 Majumdar S K, Shaw G K, Bridges P K. The dexamethasone suppression test in chronic alcoholics with and without depression and its relationship to their hepatic status.  Drug Alcohol Depend. 1988;  21 231-235
    PubMedGoogle Scholar
  • 39 Raadsheer F C, Hoogendijk W J, Stam F C, Tilders F J, Swaab D F. Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients.  Neuroendocrinology. 1994;  60 436-444
    CrossrefPubMedGoogle Scholar
  • 40 Targum S D, Wheadon D E, Chastek C T, McCabe W J, Advani M T. Dysregulation of hypothalamic-pituitary-adrenal axis function in depressed alcoholic patients.  J Affect Disord. 1982;  4 347-353
    CrossrefPubMedGoogle Scholar
  • 41 Huitinga I, Erkut Z A, van Beurden D, Swaab D F. Impaired hypothalamus-pituitary-adrenal axis activity and more severe multiple sclerosis with hypothalamic lesions.  Ann Neurol. 2004;  55 37-45
    CrossrefPubMedGoogle Scholar
  • 42 Raadscheer F C, Sluiter A A, Ravid R, Tilders F J, Swaab D F. Localization of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the human hypothalamus: age-dependent colocalization with vasopressin.  Brain Res. 1993;  615 50-62
    CrossrefPubMedGoogle Scholar
  • 43 Mejer O C, Topic B, Steenbergen P J, Jochan G, Huston J P, Oitzl M S. Correlations between hypothalamus-pituitary-adrenal axis parameters depend on age and learning capacity.  Endocrinology. 2005;  146 1372-1381
    PubMedGoogle Scholar
  • 44 Zhuo J N, Swaab D F. Activation and degeneration during aging: a morphometric study of the human hypothalamus.  Microsc Res Tech. 1999;  44 36-48
    CrossrefPubMedGoogle Scholar

Dr. Valery Grinevich

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