Skip to main content

Advertisement

Log in

Differential uptake of molecules from the circulation and CSF reveals regional and cellular specialisation in CNS detection of homeostatic signals

  • Short Communication
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The uptake of hydroxystilbamidine (OHSt, FluoroGold equivalent) and wheat germ agglutinin (WGA), into the hypothalamus, two hours after injections into either the circulation or the cerebrospinal fluid, were compared in adult rats. Following intravenous injection, OHSt was found in astrocytes of the median eminence and medial part of the arcuate nucleus whereas WGA intensely labelled the blood vessels and ependymal cells throughout the hypothalamus. In complete contrast, intracerebroventricular (icv) injection into the lateral ventricle resulted in OHSt uptake by ependymocytes and astrocytes in the area adjacent to the third ventricle, with virtually no uptake in regions taking up this dye following systematic injections, i.e., the median eminence and medial arcuate. Following icv injection WGA labelling was intense in all parts of the ependymal layer of the third ventricle, including the α- and β-tanycytes. Injections into the cisterna magna gave a different pattern of uptake with OHSt being found only in astrocytes in the ventral part of the hypothalamus lateral to the arcuate nucleus whilst WGA uptake was virtually absent. This highlights the regional and cellular specialisation for uptake of molecules from the circulation and CSF. The median eminence and medial arcuate take up molecules from the circulation, with different cell types taking up different molecules. As the CSF flows through the ventricular system, different cells lining the ventricular and subarachnoid spaces take up molecules differentially. Molecules in the CSF appear to be excluded from the median eminence and medial arcuate region.

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.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Abbott NJ (2002) Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 200:629–638

    Article  PubMed  CAS  Google Scholar 

  • Akmayev IG, Fidelina OV (1981) Tanycytes and their relation to the hypophyseal gonadotrophic function. Brain Res 210:253-260

    Article  PubMed  CAS  Google Scholar 

  • Araque A, Perea G (2004) Glial modulation of synaptic transmission in culture. Glia 47:241–248

    Article  PubMed  Google Scholar 

  • Araque A, Carmignoto G, Haydon PG (2001) Dynamic signaling between astrocytes and neurons. Annu Rev Physiol 63:795–813

    Article  PubMed  CAS  Google Scholar 

  • Araque A, Sanzgiri RP, Parpura V, Haydon PG (1999) Astrocyte-induced modulation of synaptic transmission. Can J Physiol Pharm 77:699–706

    Article  CAS  Google Scholar 

  • Bacher M, Weihe E, Dietzschold B, Meinhardt A, Vedder H, Gemsa D, Bette M (2002) Borna disease virus-induced accumulation of macrophage migration inhibitory factor in rat brain astrocytes is associated with inhibition of macrophage infiltration. Glia 37:291–306

    Article  PubMed  Google Scholar 

  • Balin BJ, Broadwell RD (1988) Transcytosis of protein through the mammalian cerebral epithelium and endothelium. I. Choroid plexus and the blood-cerebrospinal fluid barrier. J Neurocytol 17:809–826

    Article  PubMed  CAS  Google Scholar 

  • Balin BJ, Broadwell RD, Salcman M, el-Kalliny M (1986) Avenues for entry of peripherally administered protein to the central nervous system in mouse, rat, and squirrel monkey. J Comp Neurol 251:260–280

    Article  PubMed  CAS  Google Scholar 

  • Banks WA (2005) Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des 11:973–984

    Article  PubMed  CAS  Google Scholar 

  • Banks WA, Kastin AJ (1985) Peptides and the blood-brain barrier: lipophilicity as a predictor of permeability. Brain Res Bull 15:287–292

    Article  PubMed  CAS  Google Scholar 

  • Banks WA, Broadwell RD (1994) Blood to brain and brain to blood passage of native horseradish peroxidase, wheat germ agglutinin, and albumin: pharmacokinetic and morphological assessments. J Neurochem 62:2404–2419

    Article  PubMed  CAS  Google Scholar 

  • Banks WA, Kastin AJ, Huang W, Jaspan JB, Maness LM (1996) Leptin enters the brain by a saturable system independent of insulin. Peptides 17:305–311

    Article  PubMed  CAS  Google Scholar 

  • Berger UV, Hediger MA (2001) Differential distribution of the glutamate transporters GLT-1 and GLAST in tanycytes of the third ventricle. J Comp Neurol 433:101–114

    Article  PubMed  CAS  Google Scholar 

  • Bouchaud C, Le Bert M, Dupouey P (1989) Are close contacts between astrocytes and endothelial cells a prerequisite condition of a blood-brain barrier? The rat subfornical organ as an example. Biol Cell 67:159–165

    Article  PubMed  CAS  Google Scholar 

  • Broadwell RD (1989) Transcytosis of macromolecules through the blood-brain barrier: a cell biological perspective and critical appraisal. Acta Neuropathol (Berl) 79:117–128

    Article  CAS  Google Scholar 

  • Broadwell RD, Balin BJ, Salcman M (1988) Transcytotic pathway for blood-borne protein through the blood-brain barrier. Proc Natl Acad Sci U S A 85:632–636

    Article  PubMed  CAS  Google Scholar 

  • Broadwell RD, Charlton HM, Balin BJ, Salcman M (1987) Angioarchitecture of the CNS, pituitary gland, and intracerebral grafts revealed with peroxidase cytochemistry. J Comp Neurol 260:47–62

    Article  PubMed  CAS  Google Scholar 

  • Cheunsuang O, Morris R (2005) Astrocytes in the arcuate nucleus and median eminence that take up a fluorescent dye from the circulation express leptin receptors and neuropeptide Y Y1 receptors. Glia 52:228–233

    Article  PubMed  Google Scholar 

  • Davson H (1967) Physiology of the cerebrospinal fluid. J&A Churchill, London

    Google Scholar 

  • Davson H, Segal MB (1996) Blood-brain barriers. Physiology of the CSF and blood-brain barriers. CRC Press Inc., Oxford, pp 49–91

    Google Scholar 

  • Gebke E, Müller AR, Pehl U, Gerstberger R (2000) Astrocytes in sensory circumventricular organs of the rat brain express functional binding sites for endothelin. Neuroscience 97:371–381

    Article  PubMed  CAS  Google Scholar 

  • Golden PL, Pollack GM (2003) Blood-brain barrier efflux transport. J Pharm Sci 92:1739–1753

    Article  PubMed  CAS  Google Scholar 

  • Graff CL, Pollack GM (2004) Drug transport at the blood-brain barrier and the choroid plexus. Curr Drug Metab 5:95–108

    Article  PubMed  CAS  Google Scholar 

  • Gross PM (1992) Circumventricular organ capillaries. Prog Brain Res 91:219–233

    Article  PubMed  CAS  Google Scholar 

  • Johnson AK, Gross PM (1993) Sensory circumventricular organs and brain homeostatic pathways. FASEB J 7:678–686

    PubMed  CAS  Google Scholar 

  • Kastin AJ, Pan W, Maness LM, Banks WA (1999a) Peptides crossing the blood-brain barrier: some unusual observations. Brain Res 848:96–100

    Article  PubMed  CAS  Google Scholar 

  • Kastin AJ, Pan W, Maness LM, Banks WA (1999b) Peptides crossing the blood-brain barrier: some unusual observations. Brain Res 848:96–100

    Article  PubMed  CAS  Google Scholar 

  • Maness LM, Kastin AJ, Farrell CL, Banks WA (1998) Fate of leptin after intracerebroventricular injection into the mouse brain. Endocrinology 139:4556–4562

    Article  PubMed  CAS  Google Scholar 

  • Mercier C, Masseguin C, Roux F, Gabrion J, Scherrmann JM (2004) Expression of P-glycoprotein (ABCB1) and Mrp1 (ABCC1) in adult rat brain: focus on astrocytes. Brain Res 1021:32–40

    Article  PubMed  CAS  Google Scholar 

  • Pan W, Kastin AJ (2004) Polypeptide delivery across the blood-brain barrier. Curr Drug Targets CNS Neurol Disord 3:131–136

    Article  PubMed  CAS  Google Scholar 

  • Pan W, Akerstrom V, Zhang J, Pejovic V, Kastin AJ (2004) Modulation of feeding-related peptide/protein signals by the blood-brain barrier. J Neurochem 90:455–461

    Article  PubMed  CAS  Google Scholar 

  • Pardridge WM (1999) Blood-brain barrier biology and methodology. J Neurovirol 5:556–569

    Article  PubMed  CAS  Google Scholar 

  • Pardridge WM (2005) The blood-brain barrier: bottleneck in brain drug development. NeuroRx 2:3–14

    Article  PubMed  Google Scholar 

  • Perea G, Araque A (2002) Communication between astrocytes and neurons: a complex language. J Physiol Paris 96:199–207

    Article  PubMed  Google Scholar 

  • Peruzzo B, Pastor FE, Blazquez JL, Amat P, Rodríguez EM (2004) Polarized endocytosis and transcytosis in the hypothalamic tanycytes of the rat. Cell Tissue Res 317:147–164

    Article  PubMed  CAS  Google Scholar 

  • Peruzzo B, Pastor FE, Blazquez JL, Schobitz K, Pelaez B, Amat P, Rodríguez EM (2000) A second look at the barriers of the medial basal hypothalamus. Exp Brain Res 132:10–26

    Article  PubMed  CAS  Google Scholar 

  • Petrov T, Howarth AG, Krukoff TL, Stevenson BR (1994) Distribution of the tight junction-associated protein ZO-1 in circumventricular organs of the CNS. Brain Res Mol Brain Res 21:235–246

    Article  PubMed  CAS  Google Scholar 

  • Piet R, Vargova L, Sykova E, Poulain DA, Oliet SH (2004) Physiological contribution of the astrocytic environment of neurons to intersynaptic crosstalk. Proc Natl Acad Sci U S A 101:2151–2155

    Article  PubMed  CAS  Google Scholar 

  • Reiber H (2003) Proteins in cerebrospinal fluid and blood: barriers, CSF flow rate and source-related dynamics. Restor Neurol Neurosci 21:79–96

    PubMed  CAS  Google Scholar 

  • Romero MI, Phelps CJ (1997) Identification of growth hormone-releasing hormone and somatostatin neurons projecting to the median eminence in normal and growth hormone-deficient Ames dwarf mice. Neuroendocrinology 65:107–116

    Article  PubMed  CAS  Google Scholar 

  • Segal MB (2000) The choroid plexuses and the barriers between the blood and the cerebrospinal fluid. Cell Mol Neurobiol 20:183–196

    Article  PubMed  CAS  Google Scholar 

  • Segal MB (2001) Transport of nutrients across the choroids plexus. Microsc Res Tech 52:33–48

    Google Scholar 

  • Shaver SW, Pang JJ, Wainman DS, Wall KM, Gross PM (1992) Morphology and function of capillary networks in subregions of the rat tuber cinereum. Cell Tissue Res 267:437–448

    Article  PubMed  CAS  Google Scholar 

  • Silverman AJ, Witkin JW, Silverman RC, Gibson MJ (1990) Modulation of gonadotropin-releasing hormone neuronal activity as evidenced by uptake of fluorogold from the vasculature. Synapse 6:154–160

    Article  PubMed  CAS  Google Scholar 

  • Smith DE, Johanson CE, Keep RF (2004) Peptide and peptide analog transport systems at the blood-CSF barrier. Adv Drug Deliv Rev 56:1765–1791

    Article  PubMed  CAS  Google Scholar 

  • Villegas JC, Broadwell RD (1993) Transcytosis of protein through the mammalian cerebral epithelium and endothelium. II. Adsorptive transcytosis of WGA-HRP and the blood-brain and brain-blood barriers. J Neurocytol 22:67–80

    Article  PubMed  CAS  Google Scholar 

  • Wagner HJ, Pilgrim C (1974) Extracellular and transcellular transport of horseradish peroxidase (HRP) through the hypothalamic tanycyte ependyma. Cell Tissue Res 152:477–491

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Richard Morris.

Additional information

This work was supported by the EU Grant QLRT-2001-00826.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cheunsuang, O., Stewart, A.L. & Morris, R. Differential uptake of molecules from the circulation and CSF reveals regional and cellular specialisation in CNS detection of homeostatic signals. Cell Tissue Res 325, 397–402 (2006). https://doi.org/10.1007/s00441-006-0162-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-006-0162-z

Keywords

Navigation