Skip to main content
SpringerLink
Log in

Alterations in neocortical expression of nicotinic acetylcholine receptor mRNAs following unilateral lesions of the rat nucleus basalis magnocellularis

  • Full Papers
  • Published:
Journal of Neural Transmission / General Section JNT Aims and scope Submit manuscript

Summary

We investigated the effect of a unilateral lesion of the nucleus basalis magnocellularis (nbm) on the expression of nicotinic acetylcholine receptors (nAChRs) in the rat cerebral cortex. Cortical nAChR concentration as determined by [3H]nicotine binding was unaffected by the nbm lesion. Expression levels of nAChR subunit mRNAs were measured using cDNA clones coding for the receptor subunits, alpha-3, alpha-4, and beta-2. At 1 week postlesion, expression levels of alpha-4, and beta-2 were increased by an average of 82% and 19%, respectively. On the other hand, expression levels of these mRNAs on the lesioned side 4 weeks after lesioning did not differ from those on the control side. Expression of alpha-3 was not altered by the nbm lesion. These results imply regulation of nAChR transcripts by cell to cell interactions. Coincrease of alpha-4 and beta-2 transcripts may provide supporting evidence for the occurrence of supersensitivity in deafferentated cholinergic neurons.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Atack JR, Wenk GL, Wegster MV, Kellar KJ, Whitehouse PJ, Rapoport SI (1989) Bilateral changes in neocortical [3H]pirenzepine and [3H]oxotremorine-M binding following unilateral lesions of the rat nucleus basalis magnocellularis: an autoradiographic study. Brain Res 483: 367–372

    Google Scholar 

  • Arendash GW, Millard WJ, Dunn AJ, Meyer EM (1987) Long-term neuropathological and neurochemical effects of nucleus basalis lesions in the rat. Science 238: 952–956

    Google Scholar 

  • Aviv H, Leder P (1972) Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sei USA 69: 1408–1412

    Google Scholar 

  • Bartus R, Pontecorvo MJ, Flicker C, Deann RL, Figueiredo JC (1986) Behavioral recovery following bilateral lesions of the nucleus basalis does not occur spontaneously. Pharmacol Biochem Behav 24: 1287–1292

    Google Scholar 

  • Boulter J, Evans K, Goldman D, Martin G, Treco D, Heinemann S, Patrick J (1986) Isolation of a cDNA clone coding for a possible neuronal acetylcholine receptor alphasubunit. Nature 319: 368–374

    Google Scholar 

  • Boulter J, Connolly J, Deneris E, Goldman D, Heinemann S, Patrick J (1987) Functional expression of two neuronal nicotinic acetylcholine receptors from cDNA clones identifies a gene family. Proc Natl Acad Sci USA 84: 7763–7767

    Google Scholar 

  • Clarke PBS, Schwarz RD, Paul SM, Pert CB, Pert A (1985) Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alphabungarotoxin. J Neurosci 5: 1307–1315

    Google Scholar 

  • Deneris ES, Connolly J, Boulter J, Wada E, Wada K, Swanson LW, Patrick J, Heinemann S (1988) Primary structure and expression of beta 2: a novel subunit of neuronal nicotinic acetylcholine receptors. Neuron 1: 45–54

    Google Scholar 

  • Deneris ES, Boulter J, Swanson LW, Patrick J, Heinemann S (1989) Beta 3: a new member of nicotinic acetylcholine receptor gene family is expressed in brain. J Biol Chem 264: 6268–6272

    Google Scholar 

  • Evans S, Goldman D, Heinemann S, Patrick J (1987) Muscle acetylcholine receptor biosynthesis. Regulation by transcript availability. J Biol Chem 262: 4911–4916

    Google Scholar 

  • Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132: 6–13

    Google Scholar 

  • Flicker C, Dean RL, Watkins DL, Fisher SK, Bartus RT (1983) Behavioral and neurochemical effects following neurotoxic lesions of a major cholinergic input to the cerebral cortex in the rat. Pharmacol Biochem Behav 18: 973–981

    Google Scholar 

  • Flynn DD, Mash DC (1986) Characterization of L-[3H]nicotine binding in human cerebral cortex: comparison between Alzheimer's disease and the normal. J Neurochem 47: 1948–1954

    Google Scholar 

  • Fonnum F (1975) A rapid radiochemical method of the determiantion of choline acetyltransferase. J Neurochem 24: 407–409

    Google Scholar 

  • Friedman E, Lerer B, Kuster J (1983) Loss of cholinergic neurons in the rat neocortex produces deficits in passive avoidance learning. Pharmacol Biochem Behav 19: 309–312

    Google Scholar 

  • Glisin V, Crkvenjakov R, Byus C (1974) Ribonucleic acid isolated by chloride centrifugation. Biochemistry 13: 2633–2637

    Google Scholar 

  • Goldman D, Boulter J, Heinemann S, Patrick J (1985) Muscle denervation increases the levels of two mRNAs coding for the acetylcholine receptor alpha-subunit. J Neurosci 5: 2553–2558

    Google Scholar 

  • Goldman D, Simmons D, Swanson LW, Patrick J, Heinemann S (1986) Mapping of brain areas expressing RNA homologous to two different acetylcholine receptor alpha-subunit cDNA. Proc Natl Acad Sci USA 83: 4076–4080

    Google Scholar 

  • Goldman D, Deneris E, Luyten W, Kochhar A, Patrick J, Heinemann S (1987) Members of a nicotinic acetylcholine receptor gene family are expressed in different regions of the mammalian central nervous system. Cell 48: 965–973

    Google Scholar 

  • Helper DJ, Wenk GL, Cribbs BL, Olton DS, Coyle JT (1985) Memory impairments following basal forebrain lesions. Brain Res 346: 8–14

    Google Scholar 

  • Johnston MV, McKinney M, Coyle JT (1981) Neocortical cholinergic innervation: a description of extrinsic and intrinsic components in the rats. Exp Brain Res 43: 159–172

    Google Scholar 

  • Kuno M (1974) Factors in efficacy of central synapses. In: Bennet MVL (ed) Synaptic transmission and neuronal interaction. Raven Press, New York, pp 79–85

    Google Scholar 

  • Knowlton BJ, Wenk GL, Olton DS, Coyle JT (1985) Basal forebrain lesions produce a dissociation of trial-dependent and trial-independent memory performance. Brain Res 345: 315–321

    Google Scholar 

  • Ksir C, Benson DM (1983) Enhanced behavioral response to nicotine in an animal model of Alzheimer's disease. Psychopharmacology 81: 272–273

    Google Scholar 

  • Laduron P (1980) Axoplasmic transport of muscarinic receptors. Nature 286: 287–288

    Google Scholar 

  • Lamour Y, Dutar P, Jobert A (1982) Spread of acetylcholine sensitivity in the neocortex following lesion of the nucleus basalis. Brain Res 252: 377–381

    Google Scholar 

  • Lippiello PM, Fernandes KG (1986) The binding of L-[3H]nicotine to a single class of high affinity sites in rat brain membranes. Mol Pharmacol 29: 448–454

    Google Scholar 

  • LoConte G, Bartolini L, Casamenti F, Marconcini-Pepeu I, Pepeu G (1982) Lesions of cholinergic forebrain nuclei: changes in avoidance behavior and scopolamine actions. Pharmacol Biochem Behav 17: 933–937

    Google Scholar 

  • Merlie JP, Isenberg KE, Russell SD, Sances JR (1984) Denervation supersensitivity in skeletal muscle: analysis with a cloned cDNA probe. J Cell Biol 99: 332–335

    Google Scholar 

  • Meyer EM, Arendash GW, Judkins JH, Ying L, Wade C, Kem WR (1987) Effects of nucleus basalis lesions on muscarinic and nicotinic modulation of [3H]acetylcholine release in the rat cerebral cortex. J Neurochem 49: 1758–1762

    Google Scholar 

  • Millington W, Aizenman E, Bierkamper GG, Zarbin MA, Kuhar MJ (1985) Axonal transport of alpha-bungarotoxin binding sites in the rat sciatic nerve. Brain Res 340: 269–276

    Google Scholar 

  • Nakajima-Iijima S, Hamada H, Reddy P, Kakunaga T (1985) Molecular structure of the human cytoplasmic beta-actin gene: interspecies homology of sequences in the introns. Proc Natl Acad Sci USA 82: 6133–6137

    Google Scholar 

  • Ninkovic M, Hunt SP (1983) Alpha-bungarotoxin binding sites on sensory neurons and their axonal transport in sensory afferents. Brain Res 272: 57–69

    Google Scholar 

  • Nordberg A, Alafuzoff I, Winbald B (1986) Muscarinic receptor subtypes in hippocampus in Alzheimer's disease and mixed dementia type. Neurosci Lett 72: 115–121

    Google Scholar 

  • Romano C, Goldstein A (1980) Stereospecific nicotine receptors on rat brain membranes. Science 210: 647–650

    Google Scholar 

  • Salamone JD, Beart PM, Alpert JE, Iversen SD (1984) Impairment in T-maze reinforced alternation performance following nucleus basalis magnocellularis lesions in rats. Behav Brain Res 13: 63–70

    Google Scholar 

  • Santos-Bento FF, Gonzalez JL, de la Torre F (1988) Choline acetyltransferase activity in the rat brain cortex homogenate, synaptosomes, and capillaries after lesioning the nucleus basalis magnocellularis. J Neurochem 50: 395–399

    Google Scholar 

  • Schwartz RD, Lehmann J, Kellar KJ (1984) Presynaptic nicotinic cholinergic receptors labelled by [3H]acetylcholine on catecholamine and serotonin axons in brain. J Neurochem 42: 1495–1498

    Google Scholar 

  • Ueno S, Takahashi M, Hara Y, Kajiyama K, Miyai I, Tarui S (1988) Acetylcholine receptor synthesis in myasthnic rats. In: Igata A (ed) Neuroimmunological diseases. Recent advances in pathogenesis and treatment. University of Tokyo Press, Tokyo, pp 247–250

    Google Scholar 

  • Ullrich A, Shine J, Chirgwin J, Pictet R, Tischer E, Rutter WJ, Goodman HM (1977) Rat insulin genes: contruction of plasmids containing the coding sequences. Science 196: 1313–1319

    Google Scholar 

  • Vige X, Briley M (1988) Scopolamine induces up-regulation of nicotinic receptors in intact but not in nucleus basalis lesioned rats. Neurosci Lett 88: 319–324

    Google Scholar 

  • Wada E, Wada K, Boulter J, Deneris E, Heinemann S, Patrick J, Swanson LW (1989) Distribution of alpha 2, alpha 3, alpha 4 and beta 2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: a hybridization histochemical study in the rat. J Comp Neurol 284: 314–335

    Google Scholar 

  • Wada K, Ballivet M, Boulter J, Connolly J, Wada E, Deneris ES, Swanson LW, Heinemann S, Patrick J (1988) Functional expression of a new pharmacological subtype of brain nicotinic acetylcholine receptor. Science 240: 330–334

    Google Scholar 

  • Whitehouse PJ, Martino AM, Price DL, Kellar KJ (1985) Reductions in nicotinic but not muscarinic cholinergic receptors in Alzheimer's disease measured using [3H] acetylcholine. Ann Neurol 18: 145

    Google Scholar 

  • Whitehouse PJ, Martino AM, Antuono PG, Lowenstein PR, Coyle JT, Price DL, Kellar KJ (1986) Nicotinic acetylcholine sites in Alzheimer's disease. Brain Res 371: 146–151

    Google Scholar 

  • Whitehouse PJ, Martino AM, Wagster MW, Price DL, Mayeux R, Atack JR, Kellar KJ (1988) Reductions in [3H]nicotinic acetylcholine binding in Alzheimer's disease and Parkinson's disease: an autoradiographic study. Neurology 38: 720–723

    Google Scholar 

  • Whiting P, Esch F, Shimasaki S, Lindstrom J (1987) Neuronal nicotinic acetylcholine receptor beta-subunit is coded for by the cDNA clone alpha 4. FEBS Lett 219: 459–463

    Google Scholar 

Download references

Author information

Author notes

  1. I. Miyai

    Present address: Department of Neurology, Osaka University Medical School, Osaka, Japan

Authors and Affiliations

  1. Department of Neurology, Osaka University Medical School, Osaka, Japan

    S. Ueno, S. Yorifuji, H. Fujimura & S. Tarui

Authors
  1. I. Miyai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Ueno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Yorifuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Fujimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Tarui
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miyai, I., Ueno, S., Yorifuji, S. et al. Alterations in neocortical expression of nicotinic acetylcholine receptor mRNAs following unilateral lesions of the rat nucleus basalis magnocellularis. J. Neural Transmission 82, 79–91 (1990). https://doi.org/10.1007/BF01245165

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01245165

Keywords

Search

Navigation