Abstract
The blood–brain barrier (BBB) is a structural and functional barrier that prevents free exchange of circulating substances with the brain, where the endothelial cells of microvessels are joined by tight junctions. The circumventricular organs (CVOs), by contrast, lack tight junctions and exhibit more direct communication with the circulating blood and cerebrospinal fluid. Despite many outstanding morphological studies at the electron microscopic level, there remain misconceptions that the CVOs provide direct passage of blood-borne substances to the rest of the brain. This study will show the structure of the anatomical borders of the dorsal vagal complex in the brainstem. A distinct diffusion barrier between the area postrema (AP, a CVO) and the nucleus tractus solitarius (NTS) was illustrated by immunohistochemistry at both the light and electron microscopic levels. The border zone between the AP and NTS was underlined by a continuous monolayer of columnar cells that were immunopositive for both the tight junction protein zona occludin-1 and the astrocyte marker glial fibrillary acidic protein. This observation of a diffusion barrier between the AP and NTS resolves a long-standing dispute about whether the NTS is a structural extension of the AP with a leaky BBB.
Similar content being viewed by others
References
Peruzzo B, Pastor FE, Blazquez JL et al (2000) A second look at the barriers of the medial basal hypothalamus. Exp Brain Res 132:10–26
Rodriguez EM, Blazquez JL, Pastor FE et al (2005) Hypothalamic tanycytes: a key component of brain–endocrine interaction. Int Rev Cytol 247:89–164
Ganong WF (2000) Circumventricular organs: definition and role in the regulation of endocrine and autonomic function. Clin Exp Pharmacol Physiol 27:422–427
Johnson AK, Gross PM (1993) Sensory circumventricular organs and brain homeostatic pathways. FASEB J 7:678–686
Klara PM, Brizzee KR (1975) The ultrastructural morphology of the squirrel monkey area postrema. Cell Tissue Res 160:315–326
Gotow T, Hashimoto PH (1979) Fine structure of the ependyma and intercellular junctions in the area postrema of the rat. Cell Tissue Res 201:207–225
Gotow T, Hashimoto PH (1980) Fine structure of ependymal cysts in and around the area postrema of the rat. Cell Tissue Res 206:303–318
Krisch B, Leonhardt H (1978) The functional and structural border of the neurohemal region of the median eminence. Cell Tissue Res 192:327–339
Krisch B, Leonhardt H, Buchheim W (1978) The functional and structural border between the CSF- and blood-milieu in the circumventricular organs (organum vasculosum laminae terminalis, subfornical organ, area postrema) of the rat. Cell Tissue Res 195:485–497
Rethelyi M (1984) Diffusional barrier around the hypothalamic arcuate nucleus in the rat. Brain Res 307:355–358
Peruzzo B, Pastor FE, Blazquez JL et al (2004) Polarized endocytosis and transcytosis in the hypothalamic tanycytes of the rat. Cell Tissue Res 317:147–164
Maness LM, Kastin AJ, Banks WA (1998) Relative contributions of a CVO and the microvascular bed to delivery of blood-borne IL-1alpha to the brain. Am J Physiol 275:E207–E212
Kastin AJ, Pan W (2006) Editorial: intranasal leptin: blood–brain barrier bypass (BBBB) for obesity? Endocrinology 147:2086–2087
McKinley MJ, McAllen RM, Davern P et al (2003) The sensory circumventricular organs of the mammalian brain. Adv Anat Embryol Cell Biol 172:III–XII, back
Borison HL, Borison R, McCarthy LE (1984) Role of the area postrema in vomiting and related functions. Fed Proc 43:2955–2958
Miller AD, Leslie RA (1994) The area postrema and vomiting. Front Neuroendocrinol 15:301–320
Adipudi V, Simansky KJ (1995) Lesions of area postrema attenuate but do not prevent anorectic action of peripheral serotonin in rats. Am J Physiol 269:R1314–R1320
Lutz TA, Mollet A, Rushing PA et al (2001) The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema/nucleus of the solitary tract (AP/NTS) lesioned rats. Int J Obes Relat Metab Disord 25:1005–1011
Yang SJ, Lee KZ, Wu CH et al (2006) Vasopressin produces inhibition on phrenic nerve activity and apnea through V(1A) receptors in the area postrema in rats. Chin J Physiol 49:313–325
van der Kooy D, Koda LY (1983) Organization of the projections of a circumventricular organ: the area postrema in the rat. J Comp Neurol 219:328–338
Leslie RA, Gwyn DG (1984) Neuronal connections of the area postrema. Fed Proc 43:2941–2943
Shapiro RE, Miselis RR (1985) The central neural connections of the area postrema of the rat. J Comp Neurol 234:344–364
Vigier D, Portalier P (1979) Efferent projections of the area postrema demonstrated by autoradiography. Arch Ital Biol 117:308–324
Ferguson AV (1991) The area postrema: a cardiovascular control centre at the blood–brain interface? Can J Physiol Pharmacol 69:1026–1034
Hyde TM, Miselis RR (1983) Effects of area postrema/caudal medial nucleus of solitary tract lesions on food intake and body weight. Am J Physiol 244:R577–R587
Miller AD, Nonaka S (1992) Mechanisms of vomiting induced by serotonin-3 receptor agonists in the cat: effect of vagotomy, splanchnicectomy or area postrema lesion. J Pharmacol Exp Ther 260:509–517
Halatchev IG, Cone RD (2005) Peripheral administration of PYY(3-36) produces conditioned taste aversion in mice. Cell Metab 1:159–168
Zhang JV, Ren EG, Avsian-Kretchmer O et al (2005) Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science 310:996–999
Pan W, Tu H, Kastin AJ (2006) Differential BBB interactions of three ingestive peptides: obestatin, ghrelin, and adiponectin. Peptides 27:911–916
Wang QP, Nakai Y (1996) Double preembedding immunostaining for the study by electron microscopy of synaptic relationships between immunocytochemically identified neurons. In: Wouterlood FG (ed) Neuroscience protocols, module 7. Elsevier, London
Friedemann U (1942) Blood–brain barrier. Physiol Rev 223:125–145
Dempsey EW, Wislocki GB (1955) An electron microscopic study of the blood–brain barrier in the rat, employing silver nitrate as a vital stain. J Biophys Biochem Cytol 1:245–256
Van Breeman VL, Clemente CD (1955) Silver deposition in the central nervous system and the hematoencephalic barrier studied with the electron microscope. J Biophys Biochem Cytol 1:161–166
Broadwell RD, Sofroniew M (1993) Serum proteins bypass the blood–brain fluid barriers for extracellular entry to the central nervous system. Exp Neurol 120:245–263
Naylor JL, Widdowson PS, Simpson MG et al (1995) Further evidence that the blood/brain barrier impedes paraquat entry into the brain. Hum Exp Toxicol 14:587–594
Davidoff MS, Middendorff R, Kofuncu E et al (2002) Leydig cells of the human testis possess astrocyte and oligodendrocyte marker molecules. Acta Histochem 104:39–49
Banks WA, Kastin AJ (1992) Human interleukin-1α crosses the blood–testis barriers of the mouse. J Androl 13:254–259
Haug H (1971) The membrane limitans gliae superficialis of cat’s visual cortex. Z Zellforsch Mikrosk Anat 115:79–87
Petrov T, Howarth AG, Krukoff TL et al (1994) Distribution of the tight junction-associated protein ZO-1 in circumventricular organs of the CNS. Mol Brain Res 21:235–246
Wang QP, Ochiai H, Guan JL et al (1997) Ultrastructural localization of delta-1 opioid receptor in the dorsal raphe nucleus of the rat. Synapse 26:243–253
Alonso G, Tapia-Arancibia L, Assenmacher I (1985) Electron microscopic immunocytochemical study of somatostatin neurons in the periventricular nucleus of the rat hypothalamus with special reference to their relationships with homologous neuronal processes. Neuroscience 16:297–306
Wang QP, Ochiai H, Guan JL et al (1998) Ultrastructural localization of mu-1 opioid receptor in the dorsal raphe nucleus of the rat. Synapse 29:240–247
Wang QP, Zadina JE, Guan J-L et al (2002) Endomorphin-2 immunoreactivity in the cervical dorsal horn of the rat spinal cord at the electron microscopic level. Neuroscience 113:593–605
Wang QP, Zadina JE, Guan JL et al (2003) Morphological evidence of endomorphin as an agonist for the mu-opioid receptor in the rat spinal cord. Neurosci Lett 341:107–110
Wang QP, Zadina JE, Guan J-L et al (2003) Electron microscopic examination of the endomorphin 2-like immunoreactive neurons in the rat hypothalamus. Brain Res 969:126–134
Gross PM (1992) Circumventricular organ capillaries. Prog Brain Res 91:219–233
Gross PM, Wall KM, Pang JJ et al (1990) Microvascular specializations promoting rapid interstitial solute dispersion in nucleus tractus solitarius. Am J Physiol 259:R1131–R1138
Yang H, Wang L, Wu SV et al (2004) Peripheral secretin-induced Fos expression in the rat brain is largely vagal dependent. Neuroscience 128:131–141
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
Acknowledgments
Abba J. Kastin is supported by NIH DK54880, and Weihong Pan received NS45751 and NS46528. Editorial support is provided by Ms. Loula Burton.
Author information
Authors and Affiliations
Corresponding author
Additional information
Special issue article in honor of Dr. Ji-Sheng Han.
Rights and permissions
About this article
Cite this article
Wang, QP., Guan, JL., Pan, W. et al. A Diffusion Barrier Between the Area Postrema and Nucleus Tractus Solitarius. Neurochem Res 33, 2035–2043 (2008). https://doi.org/10.1007/s11064-008-9676-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-008-9676-y