Summary
Perineurial cells in the human sural nerve possess tight junctions which in freeze-fracture replicas are seen to be composed of networks of branching and anastomosing P face strands and E face grooves. Isolated circular tight junctions (maculae occludentes) may represent attachment devices between adjacent perineurial lamellae. At the overlapping margins of the cells, a beltlike tight junction (zonula occludens) encircles the cells and is believed to comprise a paracellular diffusion barrier. As the permeability of the perineurium has been found to be altered in diabetic polyneuropathy, the zonulae occludentes have been studied. In freeze-fracture replicas from cases of diabetic polyneuropathy a mixed population of structurally normal and abnormal junctions was observed. In some, the strands were abnormally curved with reduced numbers of intersections, the intervening plasma membrane displaying prominent P face concavities and E face convexities. At other sites, the junctions were severely disorganized and represented by fragmented and isolated strands with few intersections and numerous free ends. These abnormalities resemble changes that have been produced experimentally in epithelial tight junctions by osmotic damage. The possibility is considered that similar mechanisms could result in the alterations of the perineurial tight junctions in diabetic polyneuropathy and account for its impaired permeability barrier properties.
Similar content being viewed by others
References
Akert K, Sandri C, Weibel ER, Peper K, Moor M (1976) The fine structure of the perineurial endothelium. Cell Tissue Res 165:281–295
Anand P, Llewelyn JG, Thomas PK, Gillon KRW, Lisk R, Bloom SR (1988) Water content, vasoactive intestinal polypeptide and substance P in intact and crushed sciatic nerves of normal and streptozotocin-diabetic rats. J Neurol Sci 83:167–177
Breathnach AS, Martin B (1980) Freeze-fracture replication of developing intercellular contacts in perineurium in human fetal sciatic nerve. J Anat 130:640–641
Brightman MW, Hori MH, Rapoport SI, Reese TS, Westergaard E (1973) Osmotic opening of tight junctions in the cerebral endothelium. J Comp Neurol 152:317–326
Cogan DG, Kinoshita JM, Kador PF, Gerald Robinson W, Datilis MB, Cobo M, Kupfer C (1984) NIM Conference: aldose reductase and complications of diabetes. Ann Intern Med 101:82–91
DiBona DR (1985) Functional analysis of tight junction organisation. Pflüger Arch 405 [suppl]:S59-S66
Dyck PJ, Zimmerman BR, Vilen TH, Minnerath SR, Karnes JL, Yao JK, Poduslo JF (1988) Nerve glucose, fructose, sorbitol, myo-inositol, and fiber degeneration and regeneration in diabetic neuropathy. N Eng J Med 319:542–548
Fagerberg SE (1959) Diabetic neuropathy: a clinical and histological study on the significance of vascular affections. Acta Med Scand 164 [Suppl 345]:1–97
Farquhar MG, Palade GE (1963) Junctional complexes in various epithelia. J Cell Biol 17:375–412
Gabbay KH (1973) The sorbitol pathway and the complications of diabetes. N Engl J Med 288:831–836
Gabriel G, Thomas PK, King RHM, Stolinski C, Breathnach AS (1986) Freeze-fracture observations on human peripheral nerves. J Anat 146:153–166
Gabriel G, Thomas PK, King RHM, Stolinski C, Breathnach AS (1986) Peripheral nerve intramembranous particle density and distribution in chronic streptozotocin-induced diabetes in rats. Acta Neuropathol (Berl) 72:62–68
Graham AR, Johnson PC (1985) Direct immunofluorescence findings in peripheral nerve from patients with diabetic neuropathy. Ann Neurol 17:450–454
Griffey RH, Eaton RP, Sibbitt RR, Sibbit WL, Bicknell JM (1988) Diabetic neuropathy. Structural analysis of nerve hydration by magnetic resonance spectroscopy. JAMA 260: 2872–2878
Gumbiner B (1987) Structure, biochemistry and assembly of epithelial tight junctions. Am J Physiol 253:C749-C758
Jakobsen J (1978) Peripheral nerves in early experimental diabetes. Expansion of the endoneurial space as a cause of increased water content. Diabetologia 14: 113–119
Jakobsen J, Malmgren L, Olsson Y (1978) Permeability of the blood-nerve barrier in the streptozotocin-diabetic rat. Exp Neurol 60:277–285
Johnson PC, Brendel K, Meezan E (1981) Human diabetic perineurial cell basement membrane thickening. Lab Invest 44:265–370
King RHM, Llewelyn JG, Thomas PK, Gibey SG, Watkins PJ (1989) Diabetic neuropathy: abnormalities of Schwann cell and perineurial basal laminae. Implications for diabetic vasculopathy. Neuropathol Appl Neurobiol 15:339–355
Kristensson K, Olsson Y (1976) Osmotic opening of perineurial diffusion barrier in peripheral nerve. Neuropathol Appl Neurobiol 2:479–488
Krnjevic K (1955) The distribution of Na and K in cat nerves. J Physiol (Lond) 128:473–488
Llewelyn JG, Simpson CMF, Thomas PK, King RHM, Hawthorne JN (1986) Changes in sorbitol, myo-inositol and lipid inositol in dorsal root and sympathetic ganglia from streptozotocin-diabetic rats. Diabetologia 29:876–881
Llewelyn JG, Gibey SG, Thomas PK, King RHM, Muddle JR, Watkins PJ (1991) Sural nerve morphometry in diabetic autonomic and painful sensory neuropathy. Brain (in press)
Low PA (1984) Endoneurial fluid and microenvironment of nerve. In: Dyck PJ, Thomas PK, Lambert EM, Bunge R (eds) Peripheral neuropathy, 2nd edn. Saunders, Philadelphia, pp 559–617
Madara JL (1989) Loosening tight junctions. Lessons from the intestine. J Clin Invest 83:1089–1094
Madara JL, Trier JS, Neutra MR (1980) Structural changes in the plasma membrane accompanying differentiation of epithelial cells in human and monkey small intestine. Gastroenterology 78:963–975
Malik RA, Newrick PG, Sharma AK, Jennings A, Ah-See AK, Mayhew TM, Jakubowski J, Boulton ASM, Ward JD (1989) Microangiopathy in human diabetic neuropathy: a relationship between capillary abnormalities and the severity of neuropathy. Diabetologia 32:92–102
Metz J, Aoki A, Merlo M, Forsman WG (1977) Morphological alterations and functional changes of interhepatocellular junctions induced by bile duct ligation. Cell Tissue Res 182:299–310
Mizisin AP, Powell HC, Myers RR (1986) Edema and increased sodium in galactose neuropathy. Reversal with aldose reductase inhibitor. J Neurol Sci 74: 35–43
Mora-Galindo J (1986) Maturation of tight junctions in guineapig cecal epithelium. Cell Tissue Res 246:169–175
Myers RR, Keckman MM, Powell HC (1983) Endoneurial fluid is hypertonic. J Neuropathol Exp Neurol 42:217–224
Ohi T, Poduslo JF, Dyck PJ (1985) Increased endoneurial albumin in diabetic polyneuropathy. Neurology 35:1790–1791
Olsson Y (1990) Microenvironment of the peripheral nervous system under normal and pathological conditions. Crit Rev Neurobiol 5:265–311
Olsson Y, Reese TR (1971) Permeability of vasa nervorum and perineurium in mouse sciatic nerve studied by fluorescence and electron microscopy. J Neuropathol Exp Neurol 30:105–119
Pitelka DR, Taggart BN (1983) Mechanical tension induces lateral movement of intramembrane components of the tight junction: studies on mouse mammary cells in culture. J Cell Biol 96:606–612
Poduslo JF, Curran GL, Dyck PJ (1988) Increase in albumin, IgG, and IgM blood-nerve barrier indices in human diabetic neuropathy. Proc Natl Acad Sci USA 85:4879–4883
Powell DW, (1981) Barrier function in epithelia Am J Physiol 241:G275-G288
Powell HC, Costello ML, Myers RR (1981) Endoneurial fluid pressure in experimental models of diabetic neuropathy. J Neuropathol Exp Neurol 40:613–624
Reale E, Luciano L, Spitznas M (1975) Freeze-fracture faces of the perineurial sheath of the rabbit sciatic nerve. J Neurocytol 4:261–270
Rechthand E, Smith QR, Rapoport SI (1987) Transfer of nonelectrolytes from blood into peripheral nerve endoneurium. Am J Physiol 252:M1175-M1182
Seneviratne KN (1972) Permeability of blood nerve barriers in the diabetic rat. J Neurol Neurosurg Psychiatry 35: 156–162
Sharma AK, Thomas PK, Baker RWR (1976) Peripheral nerve abnormalities related to galactose administration in rats. J Neurol Neurosurg Psychiatry 39:794–802
Sima AAF, Robertson DM (1978) The perineurial and bloodnerve barriers in experimental diabetes. Acta Neuropathol (Berl) 44:189–195
Spray DC (ed) Special topic: gap junctions. (1985) Annu Rev Physiol 47:261–353
Stewart MA, Sherman WR, Kurien MM, Moonsammy GI, Wisgerhof M (1967) Polyol accumulation in nervous tissue of rats with experimental diabetes and galactosemia. J Neurochem 14:1057–1066
Stolinski C (1975) Freeze-fracture replication apparatus for biological specimens. J Microsc 104:235–244
Stolinski C, Gabriel G, Martin B (1983) Reinforcement and protection with polystyrene of freeze-fracture replicas during thawing and digestion of tissue J Microsc 132:149–152
Thomas PK (1963) The connective tissue of peripheral nerve. An electron microscope study. J Anat 97:35–44
Thomas PK, Olsson Y (1984) Microscopic anatomy and function of the connective tissue components of perpheral nerve. In: Dyck PJ, Thomas PK, Lambert EM, Bunge R (eds) Peripheral neuropathy, 2nd edn. Saunders, Philadelpia, pp 559–617
Tice LW, Carter RL, Cahill MB (1979) Changes in tight junctions of rat intestinal crypt cells associated with changes in their mitotic activity. Tissue Cell 11:293–316
Timperley WR, Boulton AJM, Jarratt JA, Davies-Jones GAB, Ward JD (1985) Small vessel disease in progressive diabetic neuropathy associated with good metabolic control. J Clin Pathol 38:1030–1038
Urakabe S, Handler JS, Orloff J (1970) Effect of hypertonicity on permeability properties of the toad bladder. Am J Physiol 218:1179–1187
Van Uijen AJ, Van Dijk SE, Koch CAM, de Vijlder JJM (1985) Freeze-fracture morphology of thyroid tight junctions in goats with different thyrotrophin stimulation. Endocrinology 116:114–118
Wade JB, Karnovsky MJ (1974) Fracture faces of osmotically disrupted zonulae occludentes. J Cell Biol 62:344–350
Wade JB, Revel JP, Discala VA (1973) Effect of osmotic gradients on intercellular junctions of the toad bladder. Am J Physiol 224: 407–415
Ward JD, Baker RWR, Davis BM (1972) Effect of blood sugar control on the accumulation of sorbitol and fructose in nerve tissue. Diabetes 21:1173–1178
Weerasuriya A, Rapoport SI Taylor RE (1979) Modification of permeability of frog perineurium to [14C]sucrose by stretch and hypertonicity. Brain Res 173:503–512
Weerasuriya A, Rapoport SI, Taylor RE (1980) Ionic permeabilities of the frog perineurium. Brain Res 191:405–415
Yasuda H, Dyck PJ (1987) Abnormalities of endoneurial microvessels and sural nerve pathology in diabetic neuropathy Neurology 37:20–29
Patel N, Misra P, Dandona P, Thomas PK (1991) The effect of nonenzymatic glycation of serum proteins on their permeation into peripheral nerve in normal and streptozotocin-diabetic rats. Diabetologia 34 (in press)
Author information
Authors and Affiliations
Additional information
Supported by the Medical Research Council and Joint Standing Research Committee of St. Mary's Hospital
Rights and permissions
About this article
Cite this article
Beamish, N.G., Stolinski, C., Thomas, P.K. et al. Freeze-fracture observations on normal and abnormal human perineurial tight junctions: alterations in diabetic polyneuropathy. Acta Neuropathol 81, 269–279 (1991). https://doi.org/10.1007/BF00305868
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00305868