The blood-brain barrier as an endocrine tissue.
Journal
Nature reviews. Endocrinology
ISSN: 1759-5037
Titre abrégé: Nat Rev Endocrinol
Pays: England
ID NLM: 101500078
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
pubmed:
28
5
2019
medline:
27
2
2020
entrez:
26
5
2019
Statut:
ppublish
Résumé
The blood-brain barrier (BBB) was first noted for its ability to prevent the unregulated exchange of substances between the blood and the central nervous system (CNS). Over time, its characterization as an interface that enables regulated exchanges between the CNS and substances that are carried in the blood in a hormone-like fashion have emerged. Therefore, communication between the CNS, BBB and peripheral tissues has many endocrine-like properties. In this Review, I examine the various ways in which the BBB exhibits endocrine-related properties. The BBB is a target for hormones, such as leptin and insulin, that affect many of its functions. The BBB is also a secretory body, releasing substances either into the blood or the interstitial fluid of the brain. The BBB selectively allows classical and non-classical hormones entry to and exit from the CNS, thus allowing the CNS to be both an endocrine target and a secretory tissue. The BBB is affected by endocrine diseases such as diabetes mellitus and can cause or participate in endocrine diseases, including those related to thyroid hormones and obesity. The endocrine-like mechanisms of the BBB can extend the definition of endocrine disease to include neurodegenerative conditions, including Alzheimer disease, and of hormones to include cytokines, triglycerides and fatty acids.
Identifiants
pubmed: 31127254
doi: 10.1038/s41574-019-0213-7
pii: 10.1038/s41574-019-0213-7
doi:
Substances chimiques
Hormones
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
444-455Références
Neuwelt, E. et al. Strategies to advance translational research into brain barriers. Lancet Neurol. 7, 84–96 (2008).
pubmed: 18093565
Davson, H. & Segal, M. B. (eds) in Physiology of the CSF and Blood–Brain Barriers 303–485 (CRC Press, Boca Raton, 1996)
Banks, W. A. in Efflux Transporters and the Blood-Brain Barrier (ed. Taylor, E. M.) 21–53 (Nova Science Publishers Inc.,2005).
Pan, W. & Kastin, A. J. Cytokine transport across the injured blood-spinal cord barrier. Curr. Pharm. Des. 14, 1620–1624 (2008).
pubmed: 18673204
pmcid: 3927781
Kastin, A. J. & Pan, W. Blood-brain barrier and feeding: Regulatory roles of saturable transport systems for ingestive peptides. Curr. Pharm. Des. 14, 1615–1619 (2008).
pubmed: 18673203
pmcid: 2750905
Banks, W. A. From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery. Nat. Rev. Drug Discov. 15, 275–292 (2016).
pubmed: 26794270
O’Donnell, M. E., Lam, T. I., Tran, L. Q., Foroutan, S. & Anderson, S. E. Estradiol reduces activity of the blood-brain barrier Na-K-Cl cotransporter and decreases edema formation in permenent middle cerebral artery occlusion. J. Cereb. Blood Flow Metab. 26, 1234–1249 (2006).
pubmed: 16421506
Guo, U. X. et al. 1,25-Dihydroxyvitamin D3 regulates expression of LRP1 and RAGE in vitro and in vivo, enhancing Abeta1 = 40 brain-to-blood efflux and peripheral uptake transport. Neruoscience 322, 28–38 (2016).
Deane, R., Wu, Z. & Zlokovic, B. V. RAGE (yin) versus LRP (yang) balance regulates Alzheimer amyloid beta-peptide clearance through transport across the blood-brain barrier. Stroke 35, 2628–2631 (2004).
pubmed: 15459432
Deane, R., Sagare, A. & Zlokovic, B. The role of the cell surface LRP and soluble LRP in blood-brain barrier A beta clearance in Alzheimer’s disease. Curr. Pharm. Des. 14, 1601–1605 (2008).
pubmed: 18673201
pmcid: 2895311
Fleegal-DeMotta, M. A., Dohgu, S. & Banks, W. A. Angiotensin II modulates BBB permeability via activation of the AT1 receptor in brain endothelial cells. J. Cereb. Blood Flow Metab. 29, 640–647 (2009).
pubmed: 19127280
Guillot, F. L. & Audus, K. L. Angiotensin peptide regulation of fluid-phase endocytosis in brain microvessel endothelial cell monolayers. J. Cereb. Blood Flow Metab. 10, 827–834 (1990).
pubmed: 2211876
Vaughan, C. J. & Delanty, N. Hypertensive emergencies. Lancet 356, 411–417 (2000).
pubmed: 10972386
Cangiano, C. et al. On the stimulation by insulin of tryptophan transport across the blood-brain barrier. Biochem. Int. 7, 617–627 (1983).
pubmed: 6091659
Daniel, P. M., Love, E. R., Moorhouse, S. R. & Pratt, O. E. The effect of insulin upon the influx of tryptophan into the brain of the rabbit. J. Physiol. 312, 551–562 (1981).
pubmed: 7021801
pmcid: 1275568
Walker, A. K., Wing, E. E., Banks, W. A. & Dantzer, R. Leucine competes with kynurenine for blood-to-brain transport and prevents lipopolysaccharide-induced depression-like behavior in mice. Mol. Psychiatry. https://doi.org/10.1038/s41380-018-0076-7 (2018).
doi: 10.1038/s41380-018-0076-7
pubmed: 30279455
pmcid: 6330090
Langston, J. W., Li, W., Harrison, L. & Aw, T. Y. Activation of promoter activity of the catalytic subunit of gamma-glutamylcysteine ligase (GCL) in brain endothelial cells by insulin requires antioxidant response element 4 and altered glycemic status: implication for GCL expression and GSH synthesis. Free Radic. Biol. Med. 51, 1749–1757 (2011).
pubmed: 21871559
pmcid: 3188337
Liu, H. et al. Insulin regulates P-glycoprotein in rat brain microvessel endothelial cells via an insulin receptor-mediated PKC/NF-kappaB pathway but not a PI3K/Akt pathway. Eur. J. Pharmacol. 602, 277–282 (2009).
pubmed: 19049803
Catalan, R. E., Martinez, A. M., Aragones, M. D., Miguel, B. G. & Robles, A. Insulin action on brain microvessels; effect on alkaline phosphatase. Biochem. Biophys. Res. Commun. 150, 583–590 (1988).
pubmed: 3277629
Kastin, A. J. & Akerstrom, V. Glucose and insulin increase the transport of leptin through the blood-brain barrier in normal mice but not in streptozotocin-diabetic mice. Neuroendocrinology 73, 237–242 (2001).
pubmed: 11340337
Ben-Shachar, D., Yehuda, S., Finberg, J. P., Spanier, I. & Youdim, M. B. Selective alteration in blood-brain barrier and insulin transport in iron-deficient rats. J. Neurochem. 50, 1434–1437 (1988).
pubmed: 2966235
May, A. A., Liu, M., Woods, S. C. & Begg, D. P. CCK increases the transport of insulin into the brain. Physiol. Behav. 165, 392–397 (2016).
pubmed: 27570192
pmcid: 5028313
Urayama, A. & Banks, W. A. Starvation and triglycerides reverse the obesity-induced impairment of insulin transport at the blood-brain barrier. Endocrinology 149, 3592–3597 (2008).
pubmed: 18403490
pmcid: 2453080
Kastin, A. J., Akerstrom, V. & Maness, L. M. Chronic loss of ovarian function decreases transport of leptin into mouse brain. Neurosci. Lett. 310, 69–71 (2001).
pubmed: 11524160
Chance, W. T., Balasubramaniam, A., Thomas, I. & Fischer, J. E. Amylin increases transport of tyrosine and tryptophan into the brain. Brain Res. 593, 20–24 (1992).
pubmed: 1281037
Banks, W. A. & Kastin, A. J. Modulation of the carrier-mediated transport of the Tyr-MIF-1 across the blood-brain barrier by essential amino acids. J. Pharmacol. Exp. Ther. 239, 668–672 (1986).
pubmed: 2879030
Urayama, A., Grubb, J. H., Banks, W. A. & Sly, W. S. Epinephrine enhances lysosomal enzyme delivery across the blood-brain barrier by up-regulation of the mannose 6-phosphate receptor. Proc. Natl Acad. Sci. USA 31, 12873–12878 (2007).
Urayama, A. et al. Alpha adrenergic induction of transport of lysosomal enzyme across the blood-brain barrier. PLOS ONE 10, e0142347 (2015).
pubmed: 26545208
pmcid: 4636227
Urayama, A., Grubb, J. H., Sly, W. S. & Banks, W. A. Pharmacologic manipulation of lysosomal enzyme transport across the blood-brain barrier. J. Cereb. Blood Flow Metab. 36, 476–476 (2016).
pubmed: 26661222
Jais, A. et al. Myeloid-cell-derived VEGF maintains brain glucose uptake and limits cognitive impairment in obesity. Cell 165, 882–895 (2016).
pubmed: 27133169
Fukuda, S. et al. Glucagon-like peptide-1 strengthens the barrier integrity in primary cultures of rat brain endothelial cells under basal and hyperglycemic conditions. J. Mol. Neurosci. 29, 211–219 (2016).
Dohgu, S. et al. Transforming growth factor-·1 upregulates the tight junction and p-glycoprotein of brain microvascular endothelial cells. Cell. Mol. Neurobiol. 24, 491–497 (2004).
pubmed: 15206827
Banks, W. A. et al. Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes 53, 1253–1260 (2004).
pubmed: 15111494
McCarthy, R. C. & Kosman, D. J. Activation of C6 glioblastoma cell ceruloplasmin expression by neighboring human brain endothelia-derived interleukins in an in vitro blood-brain barrier model system. Cell Commun. Signal 12, 65 (2014).
pubmed: 25311416
pmcid: 4200123
Yu, C., Kastin, A. J., Tu, H., Waters, S. & Pan, W. TNF activates P-glycoprotein in cerebral microvascular endothelial cells. Cell Physiol. Biochem. 20, 853–858 (2007).
pubmed: 17982267
Reyes, T. M., Fabry, Z. & Coe, C. L. Brain endothelial cell production of a neuroprotective cytokine, interleukin-6, in response to noxious stimuli. Brain Res. 851, 215–220 (1999).
pubmed: 10642846
Fabry, Z. et al. Production of the cytokines interleukin 1 and 6 by murine brain microvessel endothelium and smooth muscle pericytes. J. Neuroimmunol. 47, 23–34 (1993).
pubmed: 8376546
Kis, B. et al. Cerebral endothelial cells are a major source of adrenomedullin. J. Neuroendocrinol. 14, 283–293 (2002).
pubmed: 11963825
Mandi, Y. et al. Nitric oxide production and MDR expression by human brain endothelial cells. Anticancer Res. 18, 3049–3052 (1998).
pubmed: 9713508
Verma, S., Nakaoke, R., Dohgu, S. & Banks, W. A. Release of cytokines by brain endothelial cells: a polarized response to lipopolysaccharide. Brain Behav. Immun. 20, 449–455 (2006).
pubmed: 16309883
McGuire, T. R. et al. Release of prostaglandin E-2 in bovine brain endothelial cells after exposure to three unique forms of the antifungal drug amphotericin-B: role of COX-2 in amphotericin-B induced fever. Life Sci. 72, 2581–2590 (2003).
pubmed: 12672504
Ebling, F. J. P. & Lewis, J. E. Tanycytes and hypothalamic control of energy metabolism. Glia 66, 1176–1184 (2018).
pubmed: 29411421
Ghersi-Egea, J. F. et al. Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease. Acta Neuropathol. 35, 337–361 (2018).
Banks, W. A., Kovac, A. & Morofuji, Y. Neurovascular unit crosstalk: pericytes and astrocytes modify cytokine secretion patterns of brain endothelial cells. J. Cereb. Blood Flow Metab. 38, 1104–1118 (2018).
pubmed: 29106322
Dohgu, S., Fleegal-DeMotta, M. A. & Banks, W. A. Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood-brain barrier is mediated by luminal microvessel IL-6 and GM-CSF. J. Neuroinflamm. 8, 167 (2011).
Engstrom, L. et al. Lipopolysaccharide-induced fever depends on prostaglandin E2 production specifically in brain endothelial cells. Endocrinology 153, 4849–4861 (2012).
pubmed: 22872578
Inoue, W. et al. Brain-specific endothelial induction of prostaglandin E(2) synthesis enzymes and its temporal relation to fever. Neurosci. Res. 44, 51–61 (2002).
pubmed: 12204293
McCarthy, R. C. & Kosman, D. J. Mechanisms and regulation of iron trafficking across the capillary endothelial cells of the blood-brain barrier. Front. Mol. Neurosci. 8, 31 (2015).
pubmed: 26236187
pmcid: 4500905
Miyajima, M. et al. Organic anion transporter 3 mediates the efflux transport of an amphipathic organic anion, dehydroepiandrosterone sulfate, across the blood-brain barrier in mice. Drug Metab. Dispos. 39, 814–819 (2011).
pubmed: 21325432
David, G. F. X. & Kumar, T. C. A. Transfer of steroidal hormones from blood to the cerebrospinal fluid in the rhesus monkey. Neuroendocrinology 14, 114–120 (1974).
pubmed: 4206963
Marynick, S. P., Haven, W. W., Ebert, M. H. & Loriaux, D. L. Studies on the transfer of steroid hormones across the blood-cerebrospinal fluid barrier in Rhesus monkey. Endocrinology 99, 400–405 (1976).
pubmed: 954639
Ohtsuki, S. et al. Dominant expression of androgen receptors and their functional regulation of organic anion transporter 3 in rat brain capillary endothelial cells: comparison of gene expression between the blood-brain and -retinal barriers. J. Cell. Physiol. 204, 896–900 (2005).
pubmed: 15795901
Grube, M., Hagen, P. & Jedlitschky, G. Neurosteroid transport in the brain: role of ABC and SLC transporters. Front. Pharmacol. 9, 354 (2018).
pubmed: 29695968
pmcid: 5904994
Qaiser, M. Z. et al. Uptake and metabolism of sulphated steroids by the blood-brain barrier in the adult male rat. J. Neurochem. 142, 672–685 (2017).
pubmed: 28665486
pmcid: 5601180
Bernal, J., Guadano-Ferraz, A. & Morte, B. Thyroid hormone transporters — functions and clinical implications. Nat. Rev. Endocrinol. 11, 405–416 (2015).
Mayerl, S. et al. Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. J. Clin. Invest. 124, 1987–1999 (2014).
pubmed: 24691440
pmcid: 4001533
Roberts, L. M. et al. Expression of the thyroid hormone transporters monocarboxylate transporter-8 (SLC16A2) and organic ion transporter-14 (SLCO1C1) at the blood-brain barrier. Endocrinology 149, 6251–6261 (2008).
pubmed: 18687783
Banks, W. A., Kastin, A. J. & Michals, E. A. Transport of thyroxine across the blood-brain barrier is directed primarily from brain to blood in the mouse. Life Sci. 37, 2407–2414 (1985).
pubmed: 4079655
Kodding, R., Fuhrmann, H. & van zur Muhlen, A. Investigations on iodothyronine deiodinase activity in the maturing brain. Endocrinology 118, 1347–1352 (1986).
pubmed: 3948784
Cserr, H. F. & Berman, B. J. Iodide and thiocyanate efflux from brain following injection into rat caudate nucleus. Am. J. Physiol. 4, F331–F337 (1978).
Davson, H. & Hollingsworth, J. R. Active transport of 131 I across the blood-brain barrier. J. Physiol. 233, 327–347 (1973).
pubmed: 4355804
pmcid: 1350569
Blasberg, R. G. Methotrexate, cytosine arabinoside, and BCNU concentration in brain after ventriculocisternal perfusion. Cancer Treat Rep. 61, 625–631 (1977).
pubmed: 406995
Maness, L. M., Banks, W. A., Zadina, J. E. & Kastin, A. J. Periventricular penetration and disappearance of icv Tyr-MIF-1, DAMGO, tyrosine, and albumin. Peptides 17, 247–250 (1996).
pubmed: 8801529
Woods, S. C. & Porte, D. Jr. Relationship between plasma and cerebrospinal fluid insulin levels of dogs. Am. J. Physiol. 233, E331–E334 (1977).
pubmed: 910946
Margolis, R. U. & Altszuler, N. Insulin in the cerebrospinal fluid. Nature 215, 1375–1376 (1967).
pubmed: 6055448
Greco, A. V., Ghirlanda, G., Fedeli, G. & Gambassi, G. Insulin in the cerebro spinal fluid of man. Eur. Neurol. 3, 303–307 (1970).
pubmed: 5444536
McRory, J. E. & Sherwood, N. M. Ancient divergence of insulin and insulin-like growth factor. DNA Cell Biol. 16, 939–949 (1997).
pubmed: 9303436
Bradbury, M. W. B., Segal, M. B. & Wilson, J. Transport of potassium at the blood-brain barrier. J. Physiol. 221, 617–632 (1972).
pubmed: 5016363
pmcid: 1331355
Maness, L. M., Kastin, A. J., Farrell, C. L. & Banks, W. A. Fate of leptin after intracerebroventricular injection into the mouse brain. Endocrinology 139, 4556–4562 (1998).
pubmed: 9794465
Brief, D. J. & Davis, J. D. Reduction of food intake and body weight by chronic intraventricular insulin infusion. Brain Res. Bull. 12, 571–575 (1984).
pubmed: 6380652
McGowan, M. K., Andrews, K. M. & Grossman, S. P. Chronic intrahypothalamic infusions of insulin or insulin antibodies alter body weight and food intake in the rat. Physiol. Behav. 51, 753–766 (1992).
pubmed: 1317588
Banks, W. A. & Kastin, A. J. Physiological consequences of the passage of peptides across the blood-brain barrier. Rev. Neurosci. 4, 365–372 (1993).
pubmed: 8275277
Sandoval, D. A., Obici, S. & Seeley, R. J. Targeting the CNS to treat type 2 diabetes. Nat. Rev. Drug Discov. 8, 386–398 (2009).
pubmed: 19404312
Pocai, A. et al. Hypothalmic K(ATP) channels control hepatic glucose production. Nature 434, 1026–1031 (2005).
pubmed: 15846348
Biessels, G. J. & Reagan, L. P. Hippocampal insulin resistance and cognitive dysfunction. Nat. Rev. Neurosci. 16, 660–671 (2015).
pubmed: 26462756
Banks, W. A. Insulin in the brain: There and back again. Pharmacol. Ther. 136, 82–93 (2012).
pubmed: 22820012
pmcid: 4134675
Nelson, T. J., Sun, M. K., Hongpaisan, J. & Alkon, D. L. Insulin, PKC signaling pathways and synaptic remodeling during memory storage and neuronal repair. Eur. J. Pharmacol. 585, 76–87 (2008).
pubmed: 18402935
Biessels, G. J., Bravenboer, B. & Gispen, H. W. Glucose, insulin and the brain: modulation of cognition and synaptic plasticity in health and disease: a preface. Eur. J. Pharmacol. 490, 1–4 (2004).
pubmed: 15094068
Ferrario, C. R. & Reagan, L. P. Insulin-mediated synaptic plasticity in the CNS: anatomical, functionaland temporal contexts. Neuropharmacology 136, 182–191 (2017).
pubmed: 29217283
pmcid: 5988909
Banks, W. A., Kastin, A. J., Huang, W., Jaspan, J. B. & Maness, L. M. Leptin enters the brain by a saturable system independent of insulin. Peptides 17, 305–311 (1996).
pubmed: 8801538
Banks, W. A., Tschop, M., Robinson, S. M. & Heiman, M. L. Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J. Pharmacol. Exp. Ther. 302, 822–827 (2002).
pubmed: 12130749
Diano, S. et al. Ghrelin controls hippocampal spine synapse density and memory performance. Nat. Neurosci. 9, 381–388 (2006).
pubmed: 16491079
O’Malley, D. et al. Leptin promotes rapid dynamic changes in hippocampal dendritic morphology. Mol. Cell Neurosci. 35, 559–572 (2007).
pubmed: 17618127
pmcid: 1995039
Garza, J. C., Guo, M., Zhang, W. & Lu, X. Y. Leptin increases adult hippocampal neurogenesis in vivo and in vitro. J. Biol. Chem. 283, 18238–18247 (2008).
pubmed: 18367451
pmcid: 2440628
Greco, S. J. et al. Leptin reduces pathology and improves memory in a transgenic mouse model of Alzheimer’s disease. J. Alzheimers Dis. 19, 1155–1167 (2010).
pubmed: 20308782
pmcid: 2862270
Cuevas, P., Carceller, F., Munoz-Willery, I. & Gimenez-Gallego, G. Intravenous fibroblast growth factor penetrates the blood-brain barrier and protects hippocampal neurons against ischemia-reperfusion injury. Surg. Neurol. 49, 77–83 (1998).
pubmed: 9428898
Cuevas, P. et al. Central nervous system distribution of fibroblast growth factor injected into the blood stream. Neurol. Res. 18, 267–272 (1996).
pubmed: 8837066
Hsuchou, H., Pan, W. & Kastin, A. J. Fibroblast growth factor 19 entry into brain. Fluids Barriers CNS 10, 32 (2013).
pubmed: 24176017
pmcid: 3818657
Wagner, J. P., Black, I. B. & DiCicco-Bloom, E. Stimulation of neonatal and adult brain neurogenesis by subcutaneous injection of basic fibroblast growth factor. J. Neurosci. 19, 6006–6016 (1999).
pubmed: 10407038
Bookout, A. L. et al. FGF21 regulates metabolism and circadian behavior by acting on the nervous system. Nat. Med. 19, (1147–1152 (2013).
Lan, T. et al. FGF19, FGF21, and an FGFR1/β-klotho-activating antibody act on the nervous system to regulate body weight and glycemia. Cell Metab. 26, 709–718 (2017).
pubmed: 28988823
pmcid: 5679468
Scarlett, J. M. et al. Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents. Nat. Med. 22, 800–806 (2016).
pubmed: 27213816
pmcid: 4938755
Prevot, V. et al. The versatile tanycyte: a hypothalamic integrator of reproduction and energy metabolism. Endocr. Rev. 39, 333–368 (2018).
pubmed: 29351662
Johanson, C. E., Duncan, J. A., Stopa, E. G. & Baird, A. Enhanced prospects for drug delivery and brain targeting by the choroid plexus-CSF route. Pharm. Res. 22, 1011–1037 (2005).
pubmed: 16028003
de Lange, E. C. et al. Application of intracerebral microdialysis to study regional distribution kinetics of drug in rat brain. Br. J. Pharmacol. 116, 2538–2544 (1995).
pubmed: 8581296
pmcid: 1909064
Zlokovic, B. V. et al. Differential regulation of leptin transport by the choroid plexus and blood-brain barrier and high affinity transport systems for entry into hypothalamus and across the blood-cerebrospinal fluid barrier. Endocrinology 141, 1434–1441 (2000).
pubmed: 10746647
Nonaka, N., Hileman, S. M., Shioda, S., Vo, P. & Banks, W. A. Effects of lipopolysaccharide on leptin transport across the blood-brain barrier. Brain Res. 1016, 58–65 (2004).
pubmed: 15234252
Banks, W. A. & Farrell, C. L. Impaired transport of leptin across the blood-brain barrier in obesity is acquired and reversible. Am. J. Physiol. 285, E10–E15 (2003).
Banks, W. A. et al. Triglycerides cross the blood-brain barrier and induce central leptin and insulin receptor resistance. Int. J. Obes. (Lond.) 42, 391–397 (2018).
Romero, L. I., Kakucska, I., Lechan, R. M. & Reichlin, S. Interleukin-6 (IL-6) is secreted from the brain after intracerebroventricular injection of IL-1β in rats. Am. J. Physiol. 270, R518–R524 (1996).
pubmed: 8780215
Chen, G. & Reichlin, S. Clearance of [125 I]-tumor necrosis factor-alpha from the brain into the blood after intracerebroventricular injection into rats. Neuroimmunomodulation 5, 261–269 (1998).
pubmed: 9730694
Chen, G., McCuskey, R. S. & Reichlin, S. Blood interleukin-6 and tumor necrosis factor-alpha elevation after intracerebroventricular injection of Escherichia coli endotoxin in the rat is determined by two opposing factors: peripheral induction by LPS transferred from brain to blood and inhibition of peripheral response by a brain-mediated mechanism. Neuroimmunomodulation 8, 59–69 (2000).
pubmed: 10965230
Logsdon, A. F., Erickson, M. A., Rhea, E. M., Salameh, T. S. & Banks, W. A. Gut reactions: how the blood-brain barrier connects the microbiome and the brain. Exp. Biol. Med. (Maywood) 243, 159–165 (2018).
Erickson, M. A. & Banks, W. A. Neuroimmune axes of the blood-brain barriers and blood-brain interfaces: bases for physiological regulation, disease states, and pharmacological interventions. Pharmacol. Rev. 70, 278–314 (2018).
pubmed: 29496890
pmcid: 5833009
Sampson, T. R. et al. Gut microbioata regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 167, 1469–1480 (2016).
pubmed: 27912057
pmcid: 5718049
Starr, J. M. et al. Increased blood-brain barrier permeability in type II diabetes demonstrated by gadolinium magnetic resonance imaging. J. Neurol. Neurosurg. Psychiatry 74, 70–76 (2003).
pubmed: 12486269
pmcid: 1738177
Huber, J. D., VanGilder, R. L. & Houser, K. A. Streptozotocin-induced diabetes progressively increases blood-brain barrier permeability in specific brain regions in rats. Am. J. Physiol. 291, H2660–H2668 (2006).
Abuhaiba, S. et al. Occipital blood-brain barrier permeability is an independent predictor of visual outcome in type 2 diabetes, irrespective of the retinal barrier: a logitudinal study. J. Neuroendocrinol. 30, e12566 (2018).
Huber, J. D. Diabetes, cognitive function, and the blood-brain barrier. Curr. Pharm. Des. 14, 1594–1600 (2008).
pubmed: 18673200
Takechi, R. et al. Blood-brain barrier dysfunction precedes cognitive decline and neurodegeneration in diabetic insulin resistant mouse model: an implication for causal link. Front. Aging Neurosci. 9, 399 (2017).
pubmed: 29249964
pmcid: 5717019
Hammes, H. P. et al. Pericytes and the pathogenesis of diabetic retinopathy. Diabetes 51, 3107–3112 (2002).
pubmed: 12351455
pmcid: 12351455
Price, T. O., Eranki, V., Banks, W. A., Ercal, N. & Shah, G. N. Topiramate treatment protects blood-brain barrier pericytes from hyperglycemia-induced oxidative damage in diabetic mice. Endocrinology 153, 362–372 (2012).
pubmed: 22109883
Dore-Duffy, P. Pericytes: pluripotent cells of the blood brain barrier. Curr. Pharm. Des. 14, 1581–1593 (2008).
pubmed: 18673199
Daneman, R., Zhou, L., Kebede, A. A. & Barres, B. A. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 468, 562–566 (2010).
pubmed: 20944625
pmcid: 3241506
Zhang, Y. et al. Involvement of PUMA in pericyte migration induced by methamphetamine. Exp. Cell Res. 356, 28–39 (2017).
pubmed: 28408317
Sagare, A. P. et al. Pericyte loss influences Alzheimer-like neurodegeneration in mice. Nat. Commun. 4, 2932 (2013).
pubmed: 24336108
pmcid: 3945879
Schulz, G. B. et al. Cerebral cavernous malformation-1 protein controls DLL4-Notch3 signalling between the endothelium and pericytes. Stroke 46, 1337–1343 (2015).
pubmed: 25791711
Kaiyala, K. J., Prigeon, R. L., Kahn, S. E., Woods, S. C. & Schwartz, M. W. Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs. Diabetes 49, 1525–1533 (2000).
pubmed: 10969837
Mooradian, A. D. Blood-brain barrier choline transport is reduced in diabetic rats. Diabetes 36, 1094–1097 (1987).
pubmed: 3653526
Hong, H. et al. Downregulation of LRP1 at the blood-brain barrier in streptozotocin-induced diabetic mice. Neuropharmacology 56, 1054–1059 (2009).
pubmed: 19285094
Banks, W. A., DiPalma, C. R. & Farrell, C. L. Impaired transport of leptin across the blood-brain barrier in obesity. Peptides 20, 1341–1345 (1999).
pubmed: 10612449
Ouyang, S. et al. Diet-induced obesity suppresses expression of many proteins at the blood-brain barrier. J. Cereb. Blood Flow Metab. 34, 43–51 (2014).
pubmed: 24064496
Mooradian, A. D. & Smith, T. L. The effect of experimentally induced diabetes mellitus on the lipid order and composition of rat cerebral microvessels. Neurosci. Lett. 145, 145–148 (1992).
pubmed: 1465210
Beard, R. S. Jr, Reynolds, J. J. & Bearden, S. E. Hyperhomocysteinemia increases permeability of the blood-brain barrier by NMDA receptor-dependent regulation of adherens and tight junctions. Blood 118, 2007–2014 (2011).
pubmed: 21705496
pmcid: 3158726
Rhodehouse, B. C., Mayo, J. N., Beard, R. S. Jr, Chen, C. H. & Bearden, S. E. Opening of the blood-brain barrier before cerebral pathology in mild hyperhomocysteinemia. PLOS ONE 8, e63951 (2013).
pubmed: 23696861
pmcid: 3655957
Delange, F. The disorders induced by iodine deficiency. Thyroid 4, 107–128 (1994).
pubmed: 8054857
Nunez, B. et al. Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation. PLOS ONE 9, e96915 (2014).
pubmed: 24819605
pmcid: 4018440
Heni, M., Kullmann, S., Preissl, H., Fritsche, A. & Haring, H. U. Impaired insulin action in the human brain: causes and metabolic consequences. Nat. Rev. Endocrinol. 11, 701–711 (2015).
pubmed: 26460339
De Vivo, D. C. et al. Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N. Engl. J. Med. 325, 703–709 (1991).
pubmed: 1714544
Craft, S. et al. Cerebrosinal fluid and plasma insulin levels in Alzheimer’s disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology 50, 164–168 (1998).
pubmed: 9443474
Talbot, K. et al. Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dyregulation, and cognitive decline. J. Clin. Invest. 122, 1316–1338 (2012).
pubmed: 22476197
pmcid: 3314463
Sartorius, T. et al. The brain response to peripheral insulin declines with age: a contribution of the blood-brain barrier? PLOS ONE 10, e0126804 (2015).
pubmed: 25965336
pmcid: 4429020
Pelleymounter, M. A. et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269, 540–543 (1995).
pubmed: 7624776
Banks, W. A., Clever, C. M. & Farrell, C. L. Partial saturation and regional variation in the blood to brain transport of leptin in normal weight mice. Am. J. Physiol. 278, E1158–E1165 (2000).
Licinio, J. et al. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc. Natl Acad. Sci. USA 101, 4531–4536 (2004).
pubmed: 15070752
Ingalls, A. M., Dickie, M. M. & Snell, G. D. Obese, a new mutation in the house mouse. J. Hered. 41, 317–318 (1950).
pubmed: 14824537
Bribiescas, R. G. Serum leptin levels and anthropometric correlates in Ache Amerindians of Eastern Paraguay. Am. J. Phys. Anthropol. 115, 297–303 (2001).
pubmed: 11471127
Halaas, J. L. et al. Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc. Natl Acad. Sci. USA 94, 8878–8883 (1997).
pubmed: 9238071
van Heek, M. et al. Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J. Clin. Invest. 99, 385–390 (1997).
pubmed: 9022070
pmcid: 507810
El Haschimi, K., Pierroz, D. D., Hileman, S. M., Bjorbaek, C. & Flier, J. S. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obestiy. J. Clin. Invest. 105, 1827–1832 (2000).
pubmed: 10862798
pmcid: 378516
Rutenberg, G. W. et al. Body composition in baboons: evaluating a morphometric method. Am. J. Primatol. 12, 275–285 (1987).
Bribiescas, R. G. Serum leptin levels in Ache Amerindian females with normal adiposity are not significantly different from American anorexia nervosa patients. Am. J. Hum. Biol. 17, 207–210 (2005).
pubmed: 15736180
Kirchengast, S. Weight status of adult !Kung San and Kavango people from northern Namibia. Ann. Hum. Biol. 25, 541–551 (1996).
Schwartz, M. W. et al. Cerebrospinal fluid leptin levels: relationship to plasma levels and adiposity in humans. Nat. Med. 2, 589–593 (1996).
pubmed: 8616722
Caro, J. F. et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 348, 159–161 (1996).
pubmed: 8684156
Mantzoros, C., Flier, J. S., Lesem, M. D., Brewerton, T. D. & Jimerson, D. C. Cerebrospinal fluid leptin in anorexia nervosa: Correlation with nutritional status and potential role in resistance to weight gain. J. Clin. Endocrinol. Metab. 82, 1845–1851 (1997).
pubmed: 9177394
Smith, Q. R., Momma, S., Aoyagi, M. & Rapoport, S. I. Kinetics of neutral amino acid transport across the blood-brain barrier. J. Neurochem. 49, 1651–1658 (1987).
pubmed: 3668544
Fernstrom, J. D. Branched-chain amino acids and brain function. J. Nutr. 135, 1439S–1546S (2005).
van Spronsen, F. J., de Groot, M. J., Hoeksma, M., Reijngoud, D.-J. & van Rijn, M. Large neutral amino acids in the treatment of PKU: from theory to practice. J. Inherit. Metab. Dis. 33, 671–676 (2010).
pubmed: 20976625
pmcid: 2992655
Banks, W. A., Burney, B. O. & Robinson, S. M. Effects of triglycerides, obesity, and starvation on ghrelin transport across the blood-brain barrier. Peptides 29, 2061–2065 (2008).
pubmed: 18682266
pmcid: 2586070
Holscher, C. Novel dual GLP-1/GIP receptor agonists show neuroprotective effects in Alzheimer’s and Parkinson’s disease models. Neuropharmacology 136, 251–259 (2018).
pubmed: 29402504
Gejl, M. et al. Blood-brain glucose transfer in Alzheimer’s disease: effect of GLP-1 analog treatment. Sci. Rep. 7, 17490 (2017).
pubmed: 29235507
pmcid: 5727512
Tamargo, I. A. et al. Novel GLP-1R/GIPR co-agonist “twincretin” is neuroprotective in cell and rodent models of mild traumatic brain injury. Exp. Neurol. 288, 176–186 (2017).
pubmed: 27845037
Deli, M. A., Abraham, C. R., Kataoka, Y. & Niwa, M. Permeability studies on in vitro blood-brain barrier models: physiology, pathology, and pharmacology. Cell. Mol. Neurobiol. 25, 59–127 (2005).
pubmed: 15962509
Wolburg, H., Noell, S., Mack, A., Wolburg-Buchholz, K. & Dallier-Becker, P. Brain endothelial cells and the glio-vascular complex. Cell Tissue Res. 335, 75–96 (2009).
pubmed: 18633647
Saunders, N. R., Dziegielewska, K. M., Mollgard, K. & Habgood, M. D. Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain. J. Physiol. 596, 5723–5756 (2018).
pubmed: 29774535
pmcid: 6265560
Cornford, E. M., Braun, L. D., Oldendorf, W. H. & Hill, M. A. Comparison of lipid-mediated blood-brain-barrier penetrability in neonates and adults. Am. J. Physiol. 243, C161–C168 (1982).
pubmed: 7114247
Dickson, P. W., Aldred, A. R., Marley, P. D., Bannister, D. & Schreiber, G. Rat choroid plexus specializes in the synthesis and the secretion of transthyretin (prealbumin). Regulation of tranthyretin synthesis in choroid plexus is indpendent from that in liver. J. Biol. Chem. 15, 3475–3478 (1986).
Zhao, F. et al. Effects of passage and cryopreservation on neurotophic factor secretion from choroid plexus epithelial cells. Biomed. Rep. 8, 535–539 (2018).
pubmed: 29774144
pmcid: 5954601
Broadwell, R. D. & Sofroniew, M. V. Serum proteins bypass the blood-brain barrier for extracellular entry to the central nervous system. Exp. Neurol. 120, 245–263 (1993).
pubmed: 8491281