Anatomy and Embryology

, Volume 181, Issue 2, pp 157–166 | Cite as

Distribution of neuropeptide Y in the prosencephalon of man and Cotton-head Tamarin (Saguinus oedipus): colocalization with somatostatin in neurons of striatum and amygdala

  • M. Schwartzberg
  • J. Unger
  • A. Weindl
  • W. Lange


The presence, chromatographic properties and localization of neuropeptide Y was demonstrated in postmortem human brain areas of neurologically and neuropsychiatrically normative controls using immunocytochemistry and high performance liquid chromatography combined with radioimmunoassay. NPY-immunoreactivity was found in many regions of the prosencephalon. Numerous perikarya and fibers were present in the neocortex, basal ganglia and limbic-hypothalamic areas. A moderate number of neurons and fibers was observed in the basal forebrain, including the septal complex. A comparative immunohistochemical investigation in perfusion-fixed brains of the old-world ape Saguinus oedipus revealed an almost identical distribution of NPY-immunoreactivity with only minor differences. Colocalization experiments on 1–2 μm thin consecutive paraffin sections revealed a large number of NPY neurons throughout the human neostriatum and amygdaloid complex that were also positive for somatostatin. Our findings indicate that detection of neuropeptides in fresh or fixed post-mortem human tissue by different immunochemical methods may actually reflect the in vivo conditions. In addition, the wide distribution of NPY throughout the human brain and its colocalization with other neurotransmitters suggests a physiological role as neuroactive substance, i.e. neuromodulator in the primate central nervous system.

Key words

Neuropeptide Y Human brain Immunocytochemistry High performance liquid chromatography Colocalization 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adamo MI, Hazelwood RL (1984) Cerebellar binding of avian pancreatic polypeptide. Endocrinology 114:794–800Google Scholar
  2. Adrian TE, Allen JM, Bloom SR, Ghatei MA, Rossor MN, Roberts GW, Crow TJ, Tatemoto K, Polak JM (1983) Neuropeptide Y distribution in human brain. Nature 306:584–586Google Scholar
  3. Allen JM, Ferrier JN, Roberts GW, Cross AJ, Adrian TE, Crow TJ, Bloom SR (1980) Elevation of neuropeptide Y (NPY) in substantia innominata in Alzheimer's type dementia. J Neurol Sci 64:325–331Google Scholar
  4. Allen JM, Gibson SJ, Adrian TE, Polak JM, Bloom SR (1984a) Neuropeptidey in human spinal cord. Brain Res 308:145–148Google Scholar
  5. Allen JM, McGregor GP, Woodhams PL, Polak JM, Bloom SR (1984b) Ontogeny of a novel peptide, neuropeptide Y (NPY) in rat brain. Brain Res 303:197–200Google Scholar
  6. Allen JM, Cross AJ, Crow TJ, Javoy-Agid F, Agid A, Bloom SR (1985) Dissociation of neuropeptide Y and somatostatin in Parkinson's disease. Brain Res 337:197–200Google Scholar
  7. Allen YS, Adrian TE, Allen JM, Tatemoto K, Crow TJ, Bloom SR, Polak JM (1983) Neuropeptide Y distribution in the rat brain. Science 221:877–879Google Scholar
  8. Arimura A, Sato H, Coy DH, Schally A (1975) Radioimmunoassay for growth-hormone release inhibiting hormone. Proc Soc Exp Biol Med 148:784–789Google Scholar
  9. Beal MF, Mazurek MF, Chattha GK, Svendsen CN, Bird ED, Martin JB (1986a) Neuropeptide Y immunoreactivity is reduced in cerebral cortex in Alzheimer's disease. Ann Neurol 20:282–288Google Scholar
  10. Beal MF, Kowall NW, Ellison DW, Mazurek MF, Swartz KJ, Martin JB (1986b) Replications of the neurochemical characteristics of Huntington's disease by quinolinic acid. Nature 321:168–171Google Scholar
  11. Beal MF, Mazurek MF, Martin JB (1987) A comparison of somatostatin and neuropeptide Y distribution in monkey brain. Brain Res 405:213–219Google Scholar
  12. Chan-Palay V (1987) Localization of neuropeptides by immunocytochemistry and in vitro hybridization in human brain with special reference to coexistence. In: Elsner N, Creutzfeld O (eds) New frontiers in brain research. Proceedings of the 15th Göttingen Neurobiology Conference. Thieme, Stuttgart New York, pp 61–68Google Scholar
  13. Chan-Palay V, Yasargil G (1986a) Immunocytochemistry of human brain tissue with a polyclonal antiserum against neuropeptide Y. Anat Embryol 174:27–33Google Scholar
  14. Chan-Palay V, Allen YS, Lang W, Haesler U, Polak JM (1985a). I. Cytology and distribution in normal human cerebral cortex of neurons immunoreactive with antisera against neuropeptide Y. J Comp Neurol 238:382–389Google Scholar
  15. Chan-Palay V, Lang W, Allen YS, Haesler U, Polak JM (1985b) II. Cortical neurons immunoreactive with antisera against neuropeptide Y are altered in Alzheimer's-type dementia. J Comp Neurol 238:390–400Google Scholar
  16. Chan-Palay V, Lang W, Haesler U, Köhler C, Yasargil G (1986b) Distribution of altered hippocampal neurons and axons immunoreactive with antisera against neuropeptide Y in Alzheimer's type dementia. J Comp Neurol 248:376–394Google Scholar
  17. Chronwall BM, DiMaggio DA, Massari VJ, Pickel VM, Ruggiero DA, O'Donohue TL (1985) The anatomy of neuropeptide Y containing neurons in rat brain. Neuroscience 15:1159–1181Google Scholar
  18. Davies P, Katzman R, Terry RD (1980) Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer's disease and Alzheimer senile dementia. Nature 288:279–280Google Scholar
  19. Dawbarn D, Emson PC (1985) Neuropeptide Y-like immunoreactivity in neuritic plaques of Alzheimer's disease. Biochem Biophys Res Commun 126:289–294Google Scholar
  20. Dawbarn D, Hunt SP, Emson PC (1984) Neuropeptide Y: regional distribution, Chromatographic characterization and immunohistochemical demonstration in post-mortem human brain. Brain Res 296:168–173Google Scholar
  21. DiMaggio DA, Chronwall BM, Buchanan K, O'Donohue TL (1985) Pancreatic polypeptide immunoreactivity in rat brain is actually neuropeptide Y. Neuroscience 15:1149–1157Google Scholar
  22. Emson PC, de Quidt ME (1984) NPY a new member of the pancreatic polypeptide family. TINS 7:31–35Google Scholar
  23. Everitt BJ, Hökfelt T, Terenius L, Tatemoto K, Mutt V, Goldstein M (1984) Differential coexistence of neuropeptide Y (NPY)-like immunoreactivity with catecholamines in the central nervous system of the rat. Neuroscience 11:443–462Google Scholar
  24. Ferrante RJ, Kowall NW, Beal MF, Richardson EP, Bird ED, Martin JB (1985) Selective sparing of a class of striatal neurons in Huntington's disease. Science 230:561–563Google Scholar
  25. Fuxe K, Agnati LF, Hörfstrand A, Zini I, Tatemoto K, Pich EM, Hökfelt T, Mutt V, Terenius L (1983) Central administration of neuropeptide Y induces hypotension, bradypnea and EEG synchronization in the rat. Acta Physiol Scand 118:189–192Google Scholar
  26. Hendry SHC, Jones EG, De Felipe J, Schmechel D, Brandon C, Emson PC (1984) Neuropeptide-containing neurons of the cerebral cortex are also GABAergic. Proc Natl Acad Sci USA 81:6526–6530Google Scholar
  27. Hökfelt T, Lundberg JM, Tatemoto K, Mutt V, Terenius L, Polak J, Bloom S, Sasek C, Elde R, Goldstein M (1983) Neuropeptide Y (NPY)- and MFFRamide neuropeptide-like immunoreactivities in catecholamine neurons of the rat medulla oblongata. Acta Physiol Scand 117:315–318Google Scholar
  28. Hunt SP, Emson PC, Gilbert R, Goldstein M, Kimmel JR (1981) Presence of avian pancreatic polypeptide-like immunoreactivity in catecholamine and methionine-enkephalin-containing neurones within the central nervous system. Neurosci Lett 21:125–130Google Scholar
  29. Jacobowitz DM, Olschowka JA (1982a) Coexistence of bovine pancreatic polypeptide-like immunoreactivity and catecholamine in neurons of the ventral aminergic pathway of the rat brain. Brain Res Bull 9:391–406Google Scholar
  30. Jacobowitz DM, Olschowka JA (1982b) Bovine pancreatic polypeptide-like immunoreactivity in brain and peripheral nervous system: coexistence with catecholaminergic nerves. Brain Res Bull 3:569–590Google Scholar
  31. Jones EG, Stewart SHC (1986) The peptide containing neurons of the primate cerebral cortex. Assoc Res Nervè Ment Dis 64:163–178Google Scholar
  32. Lundberg JM, Terenius L, Hökfelt T, Martling CR, Tatemoto K, Mutt V, Polak J, Bloom S, Goldstein M (1982) Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand 116:477–480Google Scholar
  33. Lundberg JM, Saria A, Hökfelt T, Franco-Cereceda A, Terenius L (1985) Tissue-specific depletion of NPY-like immunoreactivity by reserpine. Acta Physiol Scand 123:363–365Google Scholar
  34. Maccarone C, Jarrott B (1985) Differences in regional brain concentrations of neuropeptide Y in spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. Brain Res 345:165–169Google Scholar
  35. Martel JC, St Pierre S, Quirion R (1986) Neuropeptide Y receptors in rat brain: autoradiographic localization. Peptides 7:55–60Google Scholar
  36. O'Donohue TL, Chronwall BM, Pruss RM, Mezey E, Kiss JZ, Eiden LE, Massari VJ, Tessel RE, Pickel VM, DiMaggio DA, Hotchkiss AJ, Crowley WR, Zukoska-Grojec Z (1985) Neuropeptide Y and Peptide YY neuronal and endocrine systems. Peptides 6:755–768Google Scholar
  37. Pelletier G, Desy L, Kerkerian L, Cote J (1984) Immunocytochemical localization of neuropeptide Y (NPY) in the human hypothalamus. Cell Tissue Res 238:203–205Google Scholar
  38. Sawchenko PE, Swanson LW, Grzanna R, Howe PRC, Bloom SR, Polak JM (1985) Colocalization of neuropeptide Y immunoreactivity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus. J Comp Neurol 241:138–153Google Scholar
  39. Smith Y, Parent A, Kerkerian L, Pelletier G (1985) Distribution of neuropeptide Y immunoreactivity in the basal forebrain and upper brainstem of the squirrel monkey (Saimiri sciureus). J Comp Neurol 236:71–89Google Scholar
  40. Sternberger LA (1979) Immunocytochemistry. 2nd edn. John Wiley and Sons, New York, pp. 104–169Google Scholar
  41. Tatemoto K, Carlquist M, Mutt V (1982) Neuropeptide Y — a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 296:659–660Google Scholar
  42. Tatemoto K, Siiemsmaa S, Jurnvall H, Alien JM, Polak JM, Bloom SR, Mutt V (1985) Isolation and characterization of neuropeptide Y from porcine intestine. FEBS Lett 179:181–184Google Scholar
  43. Unden A, Tatemoto K, Mutt V, Bartfai T (1984) Neuropeptide Y receptor of the rat. Eur J Biochem 145:525–530Google Scholar
  44. Unger J, Lange W (1989) Presence or absence of NADPH-diaphorase in somatostatin and neuropeptide Y neurons in amygdala and cortex: Differential sensitivity in Alzheimer's disease. Abstract, Eur J Neurosci, Suppl 2:69.6Google Scholar
  45. Unger J, Weindl A, Pitzl H, Schrell U, Lange W (1984) Antiserumproduktion gegen Somatostatin (ST): Titerkontrolle mit ELISA und Radioimmunoassay zur Bestimmung der quantitativen Verteilung von ST im Rattengehirn. Verh Anat Ges 78:515–517Google Scholar
  46. Unger JW, McNeill TH, Lapham LL, Hamill RW (1988) Neuropeptides and neuropathology in the amygdala in Alzheimer's disease: relationship between somatostatin, neuropeptide Y and subregional distribution of neuritic plaques. Brain Res 452:293–302Google Scholar
  47. Vincent SR, Skirboll L, Hökfelt T, Johansson I, Lundberg JM, Elde RP, Terenius L, Kimmel J (1982) Coexistence of somatostatin and avian pancreatic polypeptide (APP)-like immunoreactivity in some forebrain neurons. Neuroscience 7:439–446Google Scholar
  48. Vincent SR, Johansson O, Hökfelt T, Skirboll L, Elde RP, Terenius L, Kimmel J, Goldstein M (1983) NADPH-diaphorase: A selective histochemical marker for striatal neurons containing both somatostatin and avian pancreatic polypeptide (APP)-like immunoreactivities. J Comp Neurol 217:252–263Google Scholar
  49. Wood WG, Stalla G, Müller OA, Scriba PC (1979) A rapid and specific method for separation of bound and free antigen in radioimmunoassay systems. J Clin Chem Clin Biochem 17:111–114Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • M. Schwartzberg
    • 1
  • J. Unger
    • 1
  • A. Weindl
    • 2
  • W. Lange
    • 1
  1. 1.Department of AnatomyUniversity of MunichMünchenFederal Republic of Germany
  2. 2.Department of NeurologyTechnical University of MunichMünchenFederal Republic of Germany

Personalised recommendations