Aging Affects Nicotinic Acetylcholine Receptors in Brain

Author(s): Yuri N. Utkin* .

Journal Name: Central Nervous System Agents in Medicinal Chemistry

Volume 19 , Issue 2 , 2019

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Graphical Abstract:


Abstract:

Background: Aging is a common and inevitable stage in the life cycle of higher organisms. Different organs, including the central nervous system, are affected by aging in different ways. Many processes are involved in aging, and neurodegeneration is one of the aging processes in which the central nervous system is engaged. Brain degeneration during normal aging underlies cognitive disorders experienced by older people. Not all molecular mechanisms associated with age-related neurodegeneration are fully understood; however, there is a whole range of data on the participation of nicotinic acetylcholine receptors in the processes of aging and neurodegeneration. Two main subtypes of nicotinic acetylcholine receptor α7 and α4β2 present in the central nervous system are affected by these processes. The loss of these receptor subtypes during normal aging is one of the reasons for the cognitive impairments. The decrease in nicotinic acetylcholine receptors is also very important for the pathogenesis of age-related neurodegenerative diseases. Thus, the drugs enhancing receptor functions may be considered promising for the treatment of cognitive dysfunction in the aged people.

Conclusion: To achieve healthy longevity, the molecular processes that occur during aging should be established. In this regard, the participation and role of nicotinic acetylcholine receptors in the brain aging and degeneration are considered in this review.

Keywords: Aging, brain, imaging, ligand binding, neurodegeneration, neuron, neurotransmission, nicotinic acetylcholine receptor.

[1]
Bartus, R.T.; Dean, R.L. 3rd; Beer, B.; Lippa, A.S. The cholinergic hypothesis of geriatric memory dysunction. Science, 1982, 217(4558), 408-414.
[2]
Picciotto, M.R.; Zoli, M. Nicotinic receptors in aging and dementia. J. Neurobiol., 2002, 53(4), 641-655.
[3]
Court, J.A.; Lloyd, S.; Johnson, M.; Griffiths, M.; Birdsall, N.J.; Piggott, M.A.; Oakley, A.E.; Ince, P.G.; Perry, E.K.; Perry, R.H. Nicotinic and muscarinic cholinergic receptor binding in the human hippocampal formation during development and aging. Brain Res. Dev. Brain Res., 1997, 101(1-2), 93-105.
[4]
Hellström-Lindahl, E.; Court, J.A. Nicotinic acetylcholine receptors during prenatal development and brain pathology in human aging. Behav. Brain Res., 2000, 113(1-2), 159-168.
[5]
Perry, E.; Martin-Ruiz, C.; Lee, M.; Griffiths, M.; Johnson, M.; Piggott, M.; Haroutunian, V.; Buxbaum, J.D.; Nãsland, J.; Davis, K.; Gotti, C.; Clementi, F.; Tzartos, S.; Cohen, O.; Soreq, H.; Jaros, E.; Perry, R.; Ballard, C.; McKeith, I.; Court, J. Nicotinic receptor subtypes in human brain ageing, Alzheimer and Lewy body diseases. Eur. J. Pharmacol., 2000, 393(1-3), 215-222.
[6]
Zanardi, A.; Leo, G.; Biagini, G.; Zoli, M. Nicotine and neurodegeneration in ageing. Toxicol. Lett., 2002, 127(1-3), 207-215.
[7]
Ellis, J.R.; Nathan, P.J.; Villemagne, V.L.; Mulligan, R.S.; Ellis, K.A.; Tochon-Danguy, H.J.; Chan, J.G.; O’keefe, G.J.; Bradley, J.; Savage, G.; Rowe, C.C. The relationship between nicotinic receptors and cognitive functioning in healthy aging: An in vivo positron emission tomography (PET) study with 2-[(18)F]fluoro-A-85380. Synapse, 2009, 63(9), 752-763.
[8]
Mitsis, E.M.; Cosgrove, K.P.; Staley, J.K.; Bois, F.; Frohlich, E.B.; Tamagnan, G.D.; Estok, K.M.; Seibyl, J.P.; van Dyck, C.H. Age-related decline in nicotinic receptor availability with [(123)I]5-IA-85380 SPECT. Neurobiol. Aging, 2009, 30(9), 1490-1497.
[9]
Lagarde, J.; Sarazin, M.; Chauviré, V.; Stankoff, B.; Kas, A.; Lacomblez, L.; Peyronneau, M.A.; Bottlaender, M. Cholinergic Changes in Aging and Alzheimer Disease: An [18F]-F-A-85380 Exploratory PET Study. Alzheimer Dis. Assoc. Disord., 2017, 31(1), 8-12.
[10]
Sultzer, D.L.; Melrose, R.J.; Riskin-Jones, H.; Narvaez, T.A.; Veliz, J.; Ando, T.K.; Juarez, K.O.; Harwood, D.G.; Brody, A.L.; Mandelkern, M.A. Cholinergic receptor binding in alzheimer disease and healthy aging: Assessment in vivo with positron emission tomography imaging. Am. J. Geriatr. Psychiatry, 2017, 25(4), 342-353.
[11]
Mukherjee, J.; Lao, P.J.; Betthauser, T.J.; Samra, G.K.; Pan, M.L.; Patel, I.H.; Liang, C.; Metherate, R.; Christian, B.T. Human brain imaging of nicotinic acetylcholine α4β2* receptors using [18 F]Nifene: Selectivity, functional activity, toxicity, aging effects, gender effects, and extrathalamic pathways. J. Comp. Neurol., 2018, 526(1), 80-95.
[12]
Tohgi, H.; Utsugisawa, K.; Yoshimura, M.; Nagane, Y.; Mihara, M. Age-related changes in nicotinic acetylcholine receptor subunits alpha4 and beta2 messenger RNA expression in postmortem human frontal cortex and hippocampus. Neurosci. Lett., 1998, 245(3), 139-142.
[13]
Utsugisawa, K.; Nagane, Y.; Tohgi, H.; Yoshimura, M.; Ohba, H.; Genda, Y. Changes with aging and ischemia in nicotinic acetylcholine receptor subunit alpha7 mRNA expression in postmortem human frontal cortex and putamen. Neurosci. Lett., 1999, 270(3), 145-148.
[14]
Falk, L.; Nordberg, A.; Seiger, A.; Kjaeldgaard, A.; Hellström-Lindahl, E. Higher expression of alpha7 nicotinic acetylcholine receptors in human fetal compared to adult brain. Brain Res. Dev. Brain Res., 2003, 142(2), 151-160.
[15]
Coughlin, J.; Du, Y.; Rosenthal, H.B.; Slania, S.; Min Koo, S.; Park, A.; Solomon, G.; Vranesic, M.; Antonsdottir, I.; Speck, C.L.; Rootes-Murdy, K.; Lerner, A.; Rowe, S.P.; Wang, Y.; Lesniak, W.G.; Minn, I.; Bakker, A.; Smith, G.S.; Dannals, R.F.; Kuwabara, H.; Horti, A.; Wong, D.F.; Pomper, M.G. The distribution of the alpha7 nicotinic acetylcholine receptor in healthy aging: An in vivo positron emission tomography study with [18F]ASEM. Neuroimage, 2018, 65, 118-124.
[16]
Tribollet, E.; Bertrand, D.; Marguerat, A.; Raggenbass, M. Comparative distribution of nicotinic receptor subtypes during development, adulthood and aging: An autoradiographic study in the rat brain. Neuroscience, 2004, 124(2), 405-420.
[17]
Gahring, L.C.; Persiyanov, K.; Rogers, S.W. Mouse strain-specific changes in nicotinic receptor expression with age. Neurobiol. Aging, 2005, 26(6), 973-980.
[18]
Christensen, M.H.; Kohlmeier, K.A. Age-related changes in functional postsynaptic nicotinic acetylcholine receptor subunits in neurons of the laterodorsal tegmental nucleus, a nucleus important in drug addiction. Addict. Biol., 2016, 21(2), 267-281.
[19]
Narla, S.; Klejbor, I.; Birkaya, B.; Lee, Y.W.; Morys, J.; Stachowiak, E.K.; Terranova, C.; Bencherif, M.; Stachowiak, M.K. α7 nicotinic receptor agonist reactivates neurogenesis in adult brain. Biochem. Pharmacol., 2013, 86(8), 1099-1104.
[20]
Dumas, J.A.; Newhouse, P.A. The cholinergic hypothesis of cognitive aging revisited again: Cholinergic functional compensation. Pharmacol. Biochem. Behav., 2011, 99(2), 254-261.
[21]
Okada, H.; Ouchi, Y.; Ogawa, M.; Futatsubashi, M.; Saito, Y.; Yoshikawa, E.; Terada, T.; Oboshi, Y.; Tsukada, H.; Ueki, T.; Watanabe, M.; Yamashita, T.; Magata, Y. Alterations in α4β2 nicotinic receptors in cognitive decline in Alzheimer’s aetiopathology. Brain, 2013, 136(Pt 10), 3004-3017.
[22]
Tohgi, H.; Utsugisawa, K.; Yoshimura, M.; Nagane, Y.; Mihara, M. Alterations with aging and ischemia in nicotinic acetylcholine receptor subunits alpha4 and beta2 messenger RNA expression in postmortem human putamen. Implications for susceptibility to parkinsonism. Brain Res., 1998, 791(1-2), 186-190.
[23]
Tang, X.; Zhu, X.; Ding, B.; Walton, J.P.; Frisina, R.D.; Su, J. Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse. Neuroscience, 2014, 259, 184-193.
[24]
Bao, J.; Lei, D.; Du, Y.; Ohlemiller, K.K.; Beaudet, A.L.; Role, L.W. Requirement of nicotinic acetylcholine receptor subunit beta2 in the maintenance of spiral ganglion neurons during aging. J. Neurosci., 2005, 25(12), 3041-3045.
[25]
Sottile, S.Y.; Hackett, T.A.; Cai, R.; Ling, L.; Llano, D.A.; Caspary, D.M. presynaptic neuronal nicotinic receptors differentially shape select inputs to auditory thalamus and are negatively impacted by aging. J. Neurosci., 2017, 37(47), 11377-11389.
[26]
Sottile, S.Y.; Ling, L.; Cox, B.C.; Caspary, D.M. Impact of ageing on postsynaptic neuronal nicotinic neurotransmission in auditory thalamus. J. Physiol., 2017, 595(15), 5375-5385.
[27]
Utkin, Y.N.; Kryukova, E.V.; Tsetlin, V.I. What Animal Models of Parkinsonism Tell us About the Distinct Nicotinic Acetylcholine Receptors Involved in Pathogenesis? J. Alzheimers Dis. Parkinsonism, 2015, 5, 181.
[28]
Quik, M.; Zhang, D.; McGregor, M.; Bordia, T. Alpha7 nicotinic receptors as therapeutic targets for Parkinson’s disease. Biochem. Pharmacol., 2015, 97(4), 399-407.
[29]
De Jaco, A.; Bernardini, L.; Rosati, J.; Tata, A.M. Alpha-7 Nicotinic receptors in nervous system disorders: From function to therapeutic perspectives. Cent. Nerv. Syst. Agents Med. Chem., 2017, 17(2), 100-108.


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Article Details

VOLUME: 19
ISSUE: 2
Year: 2019
Page: [119 - 124]
Pages: 6
DOI: 10.2174/1871524919666190320102834

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