AGE

, Volume 35, Issue 1, pp 59–67 | Cite as

Glial molecular alterations with mouse brain development and aging: up-regulation of the Kir4.1 and aquaporin-4

Article

Abstract

Glial cells, besides participating as passive supporting matrix, are also proposed to be involved in the optimization of the interstitial space for synaptic transmission by tight control of ionic and water homeostasis. In adult mouse brain, inwardly rectifying K+ (Kir4.1) and aquaporin-4 (AQP4) channels localize to astroglial endfeets in contact with brain microvessels and glutamate synapses, optimizing clearance of extracellular K+ and water from the synaptic layers. However, it is still unclear whether there is an age-dependent difference in the expressions of Kir4.1 and AQP4 channels specifically during postnatal development and aging when various marked changes occur in brain and if these changes region specific. RT-PCR and immunoblotting was conducted to compare the relative expression of Kir4.1 and AQP4 mRNA and protein in the early and mature postnatal (0-, 15-, 45-day), adult (20-week), and old age (70-week) mice cerebral and cerebellar cortices. Expressions of Kir4.1 and AQP4 mRNA and protein are very low at 0-day. A pronounced and continuous increase was observed by mature postnatal ages (15-, 45-days). However, in the 70-week-old mice, expressions are significantly up-regulated as compared to 20-week-old mice. Both genes follow the same age-related pattern in both cerebral and cerebellar cortices. The time course and expression pattern suggests that Kir4.1 and AQP4 channels may play an important role in brain K+ and water homeostasis in early postnatal weeks after birth and during aging.

Keywords

Kir4.1 AQP4 Glia Postnatal development Aging K+ and water homeostasis 

Notes

Acknowledgments

This research was supported by a grant from the Department of Science & Technology (DST), Govt. of India, to M.S.K. RKG thanks the Council of Scientific and Industrial Research (CSIR), Govt. of India for a Junior and then a Senior Research Fellowship (CSIR Award No. File No: 09/013 (0111) 2007-EMR I).

References

  1. Barbour B, Hausser M (1997) Intersynaptic diffusion of neurotransmitter. Trends Neurosci 20:377–384PubMedCrossRefGoogle Scholar
  2. Binder DK, Oshio K, Ma T, Verkman AS (2004) Increased seizure threshold in mice lacking aquaporin-4 water channels. Neuroreport 15:259–262PubMedCrossRefGoogle Scholar
  3. Binder DK, Yao X, Zador Z, Sick TJ, Verkman AS, Manley GT (2006) Increased seizure duration and slowed potassium kinetics in mice lacking aquaporin-4 water channels. Glia 53:631–636PubMedCrossRefGoogle Scholar
  4. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254PubMedCrossRefGoogle Scholar
  5. Butt AM, Kalsi A (2006) Inwardly rectifying potassium channels (Kir) in central nervous system glia: a special role for Kir4.1 in glial functions. J Cell Mol Med 10:33–44PubMedCrossRefGoogle Scholar
  6. Connors BW, Ransom BR, Kunis DM, Gutnick MJ (1982) Activity-dependent K+ accumulation in the developing rat optic nerve. Science 216:1341–1343PubMedCrossRefGoogle Scholar
  7. Dibaj P, Kaiser M, Hirrlinger J, Kirchhoff F, Neusch C (2007) Kir4.1 channels regulate swelling of astroglial processes in experimental spinal cord edema. J Neurochem 103:2620–2628PubMedGoogle Scholar
  8. Dietzel I, Heinemann U, Hofmeier G, Lux HD (1980) Transient chaneges in the size of the extracellular space in the sensorymotor cortex of the cats in relation to stimulus-induced changes in the potassium concentration. Exp Brain Res 40:432–439PubMedCrossRefGoogle Scholar
  9. Erulkar SD, Weight FF (1977) Extracellular potassium and transmitter release at the giant synapse of the squid. J Physiol 226:209–218Google Scholar
  10. Freeman MR (2010) Specification and morphogenesis of astrocytes. Science 330:774–778PubMedCrossRefGoogle Scholar
  11. Gage PW, Quastel DMJ (1965) Dual effect of potassium on transmitter release. Nature 206:625–626PubMedCrossRefGoogle Scholar
  12. Gardner-Medwin AR (1983) A study of the mechanisms by which potassium moves through brain tissue in the rat. J Physiol 335:353–374PubMedGoogle Scholar
  13. Hayakawa N, Kato H, Araki T (2007) Age-related changes of astorocytes, oligodendrocytes and microglia in the mouse hippocampal CA1 sector. Mech Ageing Dev 128:311–316PubMedCrossRefGoogle Scholar
  14. Henderson G, Tomlinson BE, Gibson PH (1980) Cell counts in human cerebral cortex in normal adults throughout life using an image analyzing computer. J Neurol Sci 46:113–136PubMedCrossRefGoogle Scholar
  15. Holthoff K, Witte OW (1996) Intrinsic optical signals in rat neocortical slices measured with near-infrared dark-field microscopy reveal changes in extracellular space. J Neurosci 16:2740–2749PubMedGoogle Scholar
  16. Hsu MS, Seldin M, Lee DJ, Seifert G, Steinhäuser BDK (2011) Laminar-specific and developmental expression of aquaporin-4 in the mouse hippocampus. Neuroscience 178:21–32PubMedCrossRefGoogle Scholar
  17. Kanungo MS (1994) Genes and aging. Cambridge University Press, Cambridge/New York, pp 167–245CrossRefGoogle Scholar
  18. Kong H, Fan Y, Xie J, Ding J, Sha L, Shi X, Sun X, Hu G (2008) AQP4 knockout impairs proliferation, migration and neuronal differentiation of adult neural stem cells. J Cell Sci 121:4029–4036PubMedCrossRefGoogle Scholar
  19. Kullmann DM, Asztely F (1998) Extrasynaptic glutamate spillover in the hippocampus: evidence and implications. Trends Neurosci 21:8–14PubMedCrossRefGoogle Scholar
  20. Lehmenkühler A, Sykova E, Svoboda J, Zilles K, Nicholson C (1993) Extracellular space parameters in the rat neocortex and subcortical white matter during postnatal development determined by diffusion analysis. Neuroscience 55:339–351PubMedCrossRefGoogle Scholar
  21. Li J, Verkman AS (2001) Impaired hearing in mice lacking aquaporin-4 water channels. J Biol Chem 276:31233–31237PubMedCrossRefGoogle Scholar
  22. Li J, Patil RV, Verkman AS (2002) Mildly abnormal retinal function in transgenic mice without müllar cell aquaporin-4 water channels. Invest Ophthalmol Vis Sci 43:573–579PubMedGoogle Scholar
  23. Lombroso CT (1996) Neonatal seizures: a clinician's overview. Brain Dev 18:1–28PubMedCrossRefGoogle Scholar
  24. Malenka RC, Kocsis JD, Ransom BR, Waxman SG (1981) Modulation of parallel fiber excitability by postsynaptically mediated changes in extracellular potassium. Science 214:339–341PubMedCrossRefGoogle Scholar
  25. Michlewska MO, Jiang H, Aschner M, Albrecht J (2010) Gain of function of Kir4.1 channel increases cell resistance to changes of potassium fluxes and cell volume evoked by ammonia and hypoosmotic stress. Pharmacol Rep 62:1237–1242Google Scholar
  26. Modi PK, Kanungo MS (2010) Age-dependent expression of S100β in the brain of mice. Cell Mol Neurobiol 30:709–716PubMedCrossRefGoogle Scholar
  27. Nagelhus EA, Mathiisen TM, Ottersen OP (2004) Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with KIR4.1. Neuroscience 129:905–913PubMedCrossRefGoogle Scholar
  28. Neeley JD, Amiry-Moghaddam M, Ottersen OP, Froehner SC, Agre P, Adams ME (2001) Syntrophin-dependent expression and localization of aquaporin-4 water channel protein. Proc Natl Acad Sci USA 98:14108–14113CrossRefGoogle Scholar
  29. Neusch C, Rozengurt N, Jacobs RE, Lester HA, Kofuji P (2001) Kir4.1 potassium channel subunit is crucial for oligodendrocyte development and in vivo myelination. J Neurosci 21:5429–5438PubMedGoogle Scholar
  30. Niermann H, Amiry-Moghaddam M, Holthoff K, Witte OW, Ottersen OP (2001) A novel role of vasopressin in the brain: modulation of activity-dependent water flux in the neocortex. J Neurosci 21:3045–3051PubMedGoogle Scholar
  31. Padmawar P, Yao X, Bloch O, Manley GT, Verkman AS (2005) K+ waves in brain cortex visualized using a long-wavelength K+-sensing fluorescent indicator. Nat Methods 2:825–827PubMedCrossRefGoogle Scholar
  32. Pannicke T, Iandiev I, Uckermann O, Biedermann B, Kutzera F, Wiedemann P, Wolburg H, Reichenbach A, Bringmann A (2004) A potassium channel-linked mechanism of glial cell swelling in the postischemic retina. Mol Cell Neurosci 26:493–502PubMedCrossRefGoogle Scholar
  33. Papadopaulos MC, Koumenis IL, Yuan TY, Giffard RG (1997) Increased vulnerability of astrocytes to oxidative injury with age despite constant antioxidant defenses. Neuroscience 82:915–925CrossRefGoogle Scholar
  34. Ransom BR, Yamate CL, Connors BW (1985) Activity-dependent shrinkage of extracellular space in rat optic nerve: a developmental study. J Neurosci 5:525–532Google Scholar
  35. Rice D, Barone SJ (2000) Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Heal Perspect 108:511–533Google Scholar
  36. Roberts EL, Chih CP (1995) Age-related alterations in energy metabolism contribute to the increased vulnerability of the aging brain to anoxic damage. Brain Res 678:83–90PubMedCrossRefGoogle Scholar
  37. Roberts EL, Rosenthal M, Slick TJ (1990) Age-related modifications of potassium homeostasis and synaptic transmission during and after anoxia in rat hippocampal slices. Brain Res 514:111–118PubMedCrossRefGoogle Scholar
  38. Scheibel ME, Scheibel AB (1975) Structural changes in the aging brain. In: Brody H, Herman D, Ordy JM (eds) Aging, vol. 1. Raven Press, New York, pp 11–37Google Scholar
  39. Simard M, Nedergaard M (2004) The neurobiology of glia in the context of water and ion homeostasis. Neuroscience 129:877–896PubMedCrossRefGoogle Scholar
  40. Sykova E, Mazel T, Simonova Z (1998) Diffusion constraints and neuron–glia interaction during aging. Exp Gerontol 33:837–851PubMedCrossRefGoogle Scholar
  41. Takeda A, Sakurada N, Kanno S, Ando M, Oku N (2008) Vulnerability to seizure induced by dyshomeostasis in the hippocampus in aged rats. J Heal Sci 54:37–42CrossRefGoogle Scholar
  42. Takumi Y, Nagelhus EA, Eidet J, Matsubara A, Usami S, Shinkawa H, Nielsen S, Ottersen OP (1998) Select types of supporting cell in the inner ear express aquaporin-4 water channel protein. Eur J Neurosci 10:3584–3595PubMedCrossRefGoogle Scholar
  43. Venero JL, Vizuete ML, Machado A, Cano J (2001) Aquaporins in the central nervous system. Prog Neurobiol 63:321–336PubMedCrossRefGoogle Scholar
  44. Wen H, Nagelhus EA, Amiry-Moghaddam M, Agre P, Ottersen OP, Nielsen S (1999) Ontogeny of water transport in rat brain: postnatal expression of the aquaporin-4 water channel. Eur J Neurosci 11:935–945PubMedCrossRefGoogle Scholar
  45. Yasuda T, Bartlett PF, Adams DJ (2008) Kir and Kv channels regulate electrical properties and proliferation of adult neural precursor cells. Mol Cell Neurosci 37:284–297PubMedCrossRefGoogle Scholar

Copyright information

© American Aging Association 2011

Authors and Affiliations

  1. 1.Molecular Biology & Biochemistry Lab., Centre of Advance Study in ZoologyBanaras Hindu UniversityVaranasiIndia

Personalised recommendations