Skip to main content
Log in

Hypothalamic lesions in rats with long-term streptozotocin-induced diabetes mellitus

A semiquantitative light- and electron-microscopic study

  • Original Works
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Sixteen male Wistar rats, 1 year after injection of streptozotocin or vehicle, were fixed by whole-body perfusion, the brains were removed and processed for light and electron microscopy. Study of semithin sections from the hypothalamic area revealed changes in the arcuate nucleus and median eminence. The lesions, in comparison with controls, were subjected to a blind semiquantitative evaluation. The following changes were observed by light microscopy in diabetic rats: accumulation of glycogen (P<0.01), degeneration of neurons (P<0.05), hypotrophy of tanycytes (P<0.01), and axonal changes. Electron microscopy of diabetic rats revealed that glycogen was increased in neuronal bodies and processes (axons, synapses), also in tanycytes, and glia cells. In neurons were seen: dilated and fragmented endoplasmic reticulum, degranulated ergastoplasm, loss of organelles, increased number of microtubuli, myelin figures, irregulatities in the form of nuclei, and appearance of chromatin. The tanycytes in diabetic animals were reduced in volume, had an increased nuclear cytoplasmic ratio, a reduced number of organelles, short basal processes, and almost complete loss of the apical processes. These changes demonstrate the existance, under experimental conditions, of an encephalopathy pathogenetically related to streptozotocin-induced diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Akmayev G, Rabkina AE (1976a) CNS-endocrine pancreas system, I. The hypothalamus response to insulin deficiency. Endokrinologie 68:211–220

    Google Scholar 

  • Akmayev G, Rabkina AE (1976b) CNS-endocrine pancreas system. II. Response of dorsal nucleus of the vagus to insulin deficiency. Endokrinologie 68:221–225

    Google Scholar 

  • Akmayev G, Rabkina AE, Fidelina OV (1978a) CNS-endocrine pancreas system III. Further studies on the vagal responsiveness to insulin deficiency. Endokrinologie 71:169–174

    Google Scholar 

  • Akmayev G, Kabolova ZA, Rabkina AE (1978b) CNS-endocrine pancreas system. IV. Evidence for the existence of a direct hypothalamic vagal desceding pathway. Endokrinologie 71: 175–182

    Google Scholar 

  • Aronson SM, Aronson BE (1960) Intracranial vascular lesions in diabetes mellitus. J Neuropathol Exp Neurol 19:152–153

    Google Scholar 

  • Aronson SM (1973) Intracranial vascular lesions in patients with diabetes mellitus. J Neuropathol Exp Neurol 32:183–196

    Google Scholar 

  • Bischoff A, Zimmermann A (1979) Diabetic encephalopathy. Does it exist? Acta Neurol Belg 79:460–468

    Google Scholar 

  • Bodechtel G, Erbslöh F (1958) Die Veränderungen des Zentralnervensystems beim Diabetes mellitus. In: Henke F, Lubarsch O, Rössle R (eds) Handbuch der speziellen pathologischen Anatomie und Histologie, Bd 13/2, Springer, Berlin, S 1717–1739

    Google Scholar 

  • Brawer JR, Lin PS, Sonnenschein C (1974) Morphological plasticity in the wall of the third ventricle during the estrous cycle in the rat: A scanning electron-microscopic study. Anat Rec 179:481–490

    Google Scholar 

  • DeJong RN (1950) The nervous system complications of diabetes mellitus, with special reference to cerebrovascular changes. J Nerv Ment Dis 111:181–206

    Google Scholar 

  • DeJong RN (1977) CNS manifestations of diabetes mellitus. Postgrad Med 61:101–107

    Google Scholar 

  • Dierickx K, Vandesande F (1979) Immunocytochemical localization of somatostatin-containing neurons in the rat hypothalamus. Cell Tissue Res 201:349–359

    Google Scholar 

  • Hökfelt T, Fuxe K (1972) On the morphology and the neuroendocrine role of the hypothalamic catecholamine neurons. In: Knigge KM, Scott DE, Weindl A (eds) Brain-endocrine interaction. Median eminence: Structure and function. Karger, Basel, S 181–223

    Google Scholar 

  • Houssay BA, Biasotti A (1931) The hypophysis carbohydrate metabolism and diabetes. Endocrinology 15:511–523

    Google Scholar 

  • Junod A, Lambert AE, Orci L, Pictet R, Gonet AE, Renold AE (1967) Studies of the diabetogenic action of streptozotocin. Proc Soc Exp Biol Med 126:201–205

    Google Scholar 

  • Junod A, Lambert AE, Stauffacher W, Renold AE (1969) Diabetogenic action of streptozotocin: Relationship of dose to metabolic response. J Clin Invest 48:2129–2139

    Google Scholar 

  • King JC, Williams TM, Gerall AA (1974) Transformations of hypothalamic arcuate neurons. I. Changes associated with stage of estrous cycle. Cell Tissue Res 153:497–515

    Google Scholar 

  • Kordon C, Ramirez VD (1975) Recent developments in neurotransmitter-hormone interactions. In: Stumpf WE, Grant LD (eds) Anatomial neuroendocrinology, Karger, Basel, S 409–419

    Google Scholar 

  • Lapresle J (1953) Les lésions cér'ebrales au cours du diabète sucré. Arch Anat Pathol 29:145–151

    Google Scholar 

  • Long DM, Mossakowski MJ, Klatzo I (1972) Glycogen accumulation in spinal cord motor neurons due to partial ischemia. Acta Neuropathol (Berl) 20:335–347

    Google Scholar 

  • Luse SA, Gerritsen GC, Dulin WE (1970) Cerebral abnormalities in diabetes mellitus: An ultrastructural study of the brain in early onset diabetes mellitus in the Chinese hamster. Diabetologia 6:192–198

    Google Scholar 

  • Makino H, Kanatsuka A, Matsushima Y, Yamamoto M, Kumagai A, Yamaihara N (1977) Effect of streptozotocin administration on somatostatin content of pancreas and hypothalamus in rats. Endocrinol Jpn 24:295–299

    Google Scholar 

  • Mc Cann SM, Krulich L, Quijada M, Wheaton J, Moss RL (1975) Gonadotropin-releasing factors. Sites of production, secretion, and action in the brain. In: Stumpf WE, Grant LD (eds) Anatomical neuroendocrinology. Karger, Basel, S 192–199

    Google Scholar 

  • Morgan LO, Vonderahe AR, Malone EF (1937) Pathological changes in the hypothalamus in diabetes mellitus. J Nerv Ment Dis 85:125–138

    Google Scholar 

  • Mossakowski MJ, Zelman IB (1979) Glycogen deposition as an indicator of glucose metabolism disturbances in the brain due to various damaging factors. Neuropathol Pol 17:85–96

    Google Scholar 

  • Olsson Y, Säve-Söderberg J, Sourander P, Angervall L (1968) A patho-anatomical study of the central and peripheral nervous system in diabetes of early onset and long duration. Pathol Eur 3:62–79

    Google Scholar 

  • Palkovits M (1975) Isolated removal of hypothalamic nuclei for neuroendocrinological and neurochemical studies. In: Stumpf WE, Grant L (eds) Anatomical neuroendocrinology. Karger, Basel, S 72–80

    Google Scholar 

  • Pelletier G, Leclerc R, Dubé D (1979) Morphological basis of neuroendocrine function in the hypothalamus. In: Tolis G, Labrie F, Martin JB, Naftolin F (eds) Clinical neuroendocrinology: A pathophysiological approach. Raven Press, New York, S 15–27

    Google Scholar 

  • Pimstone BL, Berelowitz M (1978) Somatostatin-paracrine and neuromodulator peptide in gut and nervous system. S Afr Med J 53:7–9

    Google Scholar 

  • Prasannan KG, Subramanyan K (1968) Enzymes of glycogen metabolism in cerebral cortex of normal and diabetic rats. J Neurochem 15:1239–1241

    Google Scholar 

  • Reske-Nielsen E, Lundbaek K, (1963) Diabetic encephalopathy. Diffuse and focal lesions of the brain in long-term diabetes. Acta Neurol Scand 39 [Suppl 4]:273–290

    Google Scholar 

  • Reske-Nielsen E, Lundbaek K, Rafaelsen OJ (1965) Pathological changes in the central and peripheral nervous system of young long-term diabetics. I. Diabetic encephalopathy. Diabetologia 1:233–241

    Google Scholar 

  • Rossi GL (1975) Simple apparatus for perfusion fixation for electron microscopy. Experientia 31:998

    Google Scholar 

  • Scott DE, Paull WK (1979) The tanycyte of the rat median eminence. I. Synaptoid contacts, Cell Tissue Res 200:329–334

    Google Scholar 

  • Siler TN, Vandenberg G, Yen SSC (1973) Inhibition of growth hormone release in humans by somatostatin. J Clin Endocrinol Metab 37:632–634

    Google Scholar 

  • Warren S, Le Compte P (1952) The nervous system. In: Warren S, Le Compte P (eds) The pathology of diabetes mellitus, 3rd edn. Lea and Febiger, Philadelphia, pp 191–194

    Google Scholar 

  • Wittokowski W (1967) Zur Ultrastruktur der ependymalen Tanyzyten und Pituizyten sowie ihre synptische Verknüpfung in der Neurohypophyse des Meerschweinchens. Acta Anat 67:338–360

    Google Scholar 

  • Wright JR, Sharma H, Thibert P, Yates AP (1980) Pathologic findings in the spontaneously diabetic BB Wistar rat. Lab Invest 42:162

    Google Scholar 

  • Zimmermann EA, Hsu KC, Ferin M, Kozlowski GP (1974) Localization of gonadotropin-releasing hormone (Gn-RH) in the hypothalamus of the mouse by immunoperoxidase technique. Endocrinology 95:1–8

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by the Schweizer Nationalfonds grant No. 3. 198-0.77

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bestetti, G., Rossi, G.L. Hypothalamic lesions in rats with long-term streptozotocin-induced diabetes mellitus. Acta Neuropathol 52, 119–127 (1980). https://doi.org/10.1007/BF00688009

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00688009

Key words

Navigation