Skip to main content
Log in

Mapping of the colocalization of calretinin and tyrosine hydroxylase in the rat substantia nigra and ventral tegmental area

  • Original Paper
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

The distribution of calretinin (CR), a calcium binding protein, was compared with that of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of dopamine, throughout the rostrocaudal extent of the rat subsantia nigra (SN) and ventral tegmental area (VTA). After mapping the cells using double-labelling immunofluorescence, it was possible to distinguish three distinct cell types: cells immunoreactive for CR only, cells immunoreactive for TH only, and cells in which the two proteins were colocalized (CR+TH). Colocalized cells in rat brain sections comprised approximately 40–55% of the fluorescent labelled cells in the SN compacta, 30–40% in the VTA, and 55–80% in the SN lateralis. Colocalized cells in the SN reticulata were infrequent except in the more caudal sections where a majority of the TH-immunoreactive cells also contained CR. The percentage of CR cells that contained TH was approximately 80% in the SN compacta and averaged 65% in the VTA. Overall, the percentage of TH-immunoreactive cells which also contained CR was approximately 50% in the SN compacta and 45% in the VTA. These data reveal a significant degree of colocalization of CR in dopamine-producing cells of the SN and VTA and suggest the need for studies concerning the fate of these individual cell types following experimental manipulations.

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

  • Arai R, Winsky L, Aral M, Jacobowitz D (1991) Immunohistochemical localization of calretinin in the rat hindbrain. J Comp Neurol 310:21–44

    Google Scholar 

  • Bankiewicz KS, Plunkett RJ, Jacobowitz DM, Porrino L, di Porzio U, London WT, Kopin IJ, Oldfield EH (1990) The effect of fetal mesencephalon implants on primate MPTP-induced parkinsonism: histochemical and behavioral studies. J Neurosurg 72:231–244

    Google Scholar 

  • Bankiewicz KS, Plunkett RJ, Jacobowitz DM, Kopin IJ, Oldfield EH (1991) Fetal nondopaminergic neural implants in parkinsonian primates: histochemical and behavioral studies. J Neurosurg 74:97–104

    Google Scholar 

  • Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DJ, Kopin IJ (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 80:4546–4550

    Google Scholar 

  • Campbell KJ, Takada M (1989) Bilateral tectal projection of single nigrostriatal dopamine cells in the rat. Neuroscience 33:311–321

    Google Scholar 

  • Chronister RB, Waldins JS, Aldo LD, Marco LA (1988) Interconnections between SN reticulata and medullary reticular formation. Brain Res Bull 21:313–317

    Google Scholar 

  • Clavier RM, Atmadja S, Fibiger HC (1976) Nigrothalamic projections in the rat is demonstrated by orthograde and retrograde tracing techniques. Brain Res Bull 1:379–384

    Google Scholar 

  • Fallon JH, Loughlin SE (1985) Substantia nigra. In: Paxinos G (eds) The rat nervous system, vol I. Academic, Sydney, pp 353374

    Google Scholar 

  • Fallon JH, Moore RY (1978) Catecholamine innervation of the basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and neostriatum. J Comp Neurol 180:545–580

    Google Scholar 

  • Gerfen CR, Baimbridge KG, Miller JJ (1985) The neostriatal mosaic: compartmental distribution of calcium binding protein and parvalbumin in the basal ganglia of the rat and monkey. Proc Natl Acad Sci USA 82:8780–8784

    Google Scholar 

  • Gerfen CR, Herkenham M, Thibault J (1987a) The neostriatal mosaic. II. Patch- and matrix-directed mesostriatal dopaminergic and non-dopaminergic systems. J Neurosci 7:3915–3934

    Google Scholar 

  • Gerfen C, Baimbridge K, Thibault J (1987b) The neostriatal mosaic. III. Biochemical and developmental dissociation of patch-matrix mesostrial systems. J Neurosci 7:3935–3944

    Google Scholar 

  • German DC, Manaye KF, Sonsalla PK, Brooks BA (1992) Midbrain dopaminergic cell loss in Parkinson's disease and MPTP-induced parkinsonism: sparing of calbindin-D28K-containing cells. Ann NY Acad Sci 648:42–62

    Google Scholar 

  • Hallman H, Lange J, Olson L, Strömberg I, Jonsson G (1985) Neurochemical and histochemical characterization of neurotoxic effects of 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine on brain catecholamine neurones in the mouse. J Neurochem 44:117–127

    Google Scholar 

  • Hof P, Morrison JH (1991) Neocortical neuronal subpopulations labeled by a monoclonal antibody to calbindin exhibit differential vulnerability in Alzheimer's disease. Exp Neurol 111:293–301

    Google Scholar 

  • Hökfelt T, Johansson O, Fuxe K, Goldstein M, Park D (1976) Immunohistochemical studies on the localization and distribution of monoamine neuron systems in the rat brain. I. Tyrosine hydroxylase in the mes- and diencephalon. Med Biol 54:427–453

    Google Scholar 

  • Hökfelt T, Johansson O, Goldstein M (1984a) Chemical anatomy of the brain. Science 225:1326–1334

    Google Scholar 

  • Hökfelt T, Martensson R, Björklund A, Kleinau S, Goldstein M (1984b) Distributional maps of tyrosine hydroxylase-immunoreactive neurons in the rat brain. In: Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy, vol 2. Eisevier, Amsterdam pp 55–115

    Google Scholar 

  • Iacopino AM, Christakos S (1990) Specific reduction of calciumbinding protein (28-kilodalton calbindin-D) gene expression in aging and neurodegenerative diseases. Proc Natl Acad Sci USA 87:4078–4082

    Google Scholar 

  • Ichimiya Y, Emson PC, Mountjoy CQ, Lawson DEM, Heizmann CW (1988) Eoss of calbindin-28K immunoreactive neurones from the cortex in Alzheimer-type dementia. Brain Res 475:156–159

    Google Scholar 

  • Jacobowitz D, Winsky E (1991) Immunocytochemical localization of calretinin in the forebrain of the rat. J Comp Neurol 304:198–218

    Google Scholar 

  • Jacobowitz DJ, Burns RS, Chuang C, Chiueh CC, Kopin I (1984) N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes destruction of the nigrostriatal but not the mesolimbic dopamine system in the monkey. Psychopharmacol Bull 20:416–422

    Google Scholar 

  • Juraska JM, Wilson CJ, Groves PM (1977) The substantia nigra of the rat: a Golgi study. J Comp Neurol 172:585–600

    Google Scholar 

  • Kobayashi K, Emson PC, Mountjoy CQ, Thornton SN, Eawson DEM, Mann DMA (1990) Cerebral cortical calbindin D28K and parvalbumin neurones in Down's syndrome. Neurosci Lett 113:17–22

    Google Scholar 

  • Eavoie B, Parent A (1991) Dopaminergic neurons expressing calbindin in normal and parkinsonian monkeys. Neuroreport 2:601–604

    Google Scholar 

  • Moriizumi T, Leduc-Cross B, Wu J-Y, Hattori T (1992) Separate neuronal populations of the rat substantia nigra pars lateralis with distinct projection sites and transmitter phenotypes. Neuroscience 43:711–720

    Google Scholar 

  • Parmentier M, Lefort A (1991) Structure of the human brain calcium-binding protein calretinin and its expression in bacteria. Eur J Biochem 196:79–85

    Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd edn. Academic, Sydney

    Google Scholar 

  • Pickel VM, Joh TH, Field PM, Becker CG, Reis DJ (1975) Cellular localization of tyrosine hydroxylase by immunohistochemistry. J Histochem Cytochem 23:1–12

    Google Scholar 

  • Résibois A, Rogers JH (1992) Calretinin in rat brain: an immunohistochemical study. Neuroscience 46:101–134

    Google Scholar 

  • Ribak CE, Vaughn JE, Roberts E (1980) GABAergic nerve terminals decrease in the substantia nigra following hemitransections of the striatonigral and pallidonigral pathways. Brain Res 192:413–420

    Google Scholar 

  • Rogers JH (1987) Calretinin: a gene for a novel calcium binding protein expressed principally in neurons. J Cell Biol 105:1343–1353

    Google Scholar 

  • Rogers JH (1992) Immunohistochemical markers in rat brain: colocalization of calretinin and calbindin-D28K with tyrosine hydroxylase. Brain Res 587:203–210

    Google Scholar 

  • Rogers JH, Résibois A (1992) Calretinin and calbindin D28K in rat brain: patterns of partial colocalization. Neuroscience 51:843–865

    Google Scholar 

  • Seto-Ohshima A, Emson PC, Eawson E, Mountjoy CQ, Carrasco EH (1988) Eoss of matrix calcium-binding protein-containing neurons in Huntington's disease. Eancet 1(8597):1252–1256

    Google Scholar 

  • Sun CJ, Johannessen JN, Gessner W, Namura I, Singhaniyom W, Brossi A, Chiueh CC (1988) Neurotoxic damage to the nigrostriatal system in rats following intranigral administration of MPDP+ and MPP+. J Neural Transm 74:75–86

    Google Scholar 

  • Sutherland MK, Wong E, Somerville MJ, Yoong EKK, Bergeron C, Parmentier M, McEachlan DR (1993) Reduction of calbindin-28k mRNA levels in Alzheimer as compared to Huntington hippocampus. Mol Brain Res 18:32–42

    Google Scholar 

  • Trump BF, Berezesky IK (1992) The role of cytosolic Ca2+ in cell injury, necrosis and apoptosis. Curr Opin Cell Biol 4:227–232

    Google Scholar 

  • Winsky E, Nakata H, Martin B, Jacobowitz D (1989) Isolation, partial amino acid sequence and immunohistochemical localization of a brain-specific calcium binding protein. Proc Natl Acad Sci USA 86:10139–10143

    Google Scholar 

  • Yamada T, McGeer P, Baimbridge K, McGeer E (1990) Relative sparing in Parkinson's disease of substantia nigra dopamine neurons containing calbindin-D28K. Brain Res 526:303–307

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Isaacs, K.R., Jacobowitz, D.M. Mapping of the colocalization of calretinin and tyrosine hydroxylase in the rat substantia nigra and ventral tegmental area. Exp Brain Res 99, 34–42 (1994). https://doi.org/10.1007/BF00241410

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00241410

Key words

Navigation