Nicotinic α7 receptors protect against glutamate neurotoxicity and neuronal ischemic damage

Shimohama, Shun; Greenwald, D. L.; Shafron, David; Akaika, A.; Maeda, Takehiko; Kaneko, Shuji; Kimura, Jun; Simpkins, Christopher E.; Day, Arthur L.; Meyer, Edwin M.

doi:10.1016/s0006-8993(97)00194-7

Cited by 126 publications

(75 citation statements)

References 12 publications

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“…25) On the other hand, apoptosis is a process characterized by cell shrinkage, membrane blebbing, nuclear pyknosis, chromatin condensation and genomic fragmentation. 26,27) It has been established, through many previous studies, that stimulation of nicotinic receptor protects against glutamate- 21,[28][29][30] and amyloid-b protein- 28,31,32) induced neuronal death. Nicotinic receptors are members of a heterogeneous family of ligand-gated cation-selective ion channels that are assembled as a homomeric or heteromeric pentamer from 12 types of subunits: nine a (a2-a10) and three b (b2-b4).…”

Section: Roles Of Nicotinic Receptors In Acetylcholinesterase Inhibitmentioning

confidence: 99%

Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation

Takada‐Takatori

Kume

Izumi

et al. 2009

Biological & Pharmaceutical Bulletin

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Protection of neurons from neuronal damage and cell death in neurodegenerative disease is a major challenge in neuroscience research. Donepezil, galantamine and tacrine are acetylcholinesterase inhibitors used for the treatment of Alzheimer's disease, and were believed to be symptomatic drugs whose therapeutic effects are achieved by slowing the hydrolysis of acetylcholine at synaptic termini. However, recent accumulated evidence strongly suggests that these acetylcholinesterase inhibitors also possess neuroprotective properties whose mechanism is independent of acetylcholinesterase inhibition. We have shown that acetylcholinesterase inhibitors protect neurons from glutamate-induced neurotoxicity in the primary culture of rat cortical neurons. It was also found that acetylcholinesterase inhibitor treatment induces up-regulation of nicotinic receptor expression levels, a property which may also have some bearing on their therapeutic effects. We next showed that a a4 and a a7-nicotinic receptors play important roles in acetylcholinesterase inhibitor-induced neuroprotection and nicotinic receptor up-regulation. Our results also demonstrate the important roles of the phosphatidylinositol 3-kinase pathway downstream of nicotinic receptors in protecting neurons from death and up-regulating nicotinic receptors. This review summarizes recent findings on the roles of the nicotinic receptor in acetylcholinesterase inhibitor-induced neuroprotection and nicotinic receptor up-regulation.

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Section: Roles Of Nicotinic Receptors In Acetylcholinesterase Inhibitmentioning

confidence: 99%

Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation

Takada‐Takatori

Kume

Izumi

et al. 2009

Biological & Pharmaceutical Bulletin

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“…For this latter unique effect, there may be a significant contribution from nicotineinduced neuronal damage. Nicotine selectively upregulates striatal a7nAChRs in adolescent rats , the subtype associated with plasticity and responses to damage (Broide and Leslie, 1999;Shimohama et al, 1998). Both smoking and nicotine release large concentrations of dopamine in the striatum (Brody et al, 2004), leading to oxidative damage (Qiao et al, 2005), as is characteristic of this neurotransmitter (Olanow and Arendash, 1994).…”

Section: Effects Of Prenatal Nicotine Exposure On the Response To Nicmentioning

confidence: 99%

Prenatal Nicotine Exposure Alters the Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence: Serotonin Receptors and Cell Signaling

Slotkin

Tate

Cousins

et al. 2005

Neuropsychopharmacol

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Offspring of women who smoke during pregnancy are themselves more likely to take up smoking in adolescence, effects that are associated with a high rate of depression and increased sensitivity to withdrawal symptoms. To evaluate the biological basis for this relationship, we assessed effects on serotonin (5-hydroxytryptamine, 5HT) receptors and 5HT-mediated cellular responses in rats exposed to nicotine throughout prenatal development and then given nicotine in adolescence (postnatal days PN30-47.5), using regimens that reproduce plasma nicotine levels found in smokers. Evaluations were then made during the period of adolescent nicotine treatment and for up to one month after the end of treatment. Prenatal nicotine exposure, which elicits damage to 5HT projections in the cerebral cortex and striatum, produced sex-selective changes in the expression of 5HT 1A and 5HT 2 receptors, along with induction of adenylyl cyclase (AC), leading to sensitization of heterologous inputs operating through this signaling pathway. Superimposed on these effects, the AC response to 5HT was shifted toward inhibition. By itself, adolescent nicotine administration, which damages the same pathways, produced similar effects on receptors and the 5HT-mediated response, but a smaller overall induction of AC. Animals exposed to prenatal nicotine showed a reduced response to nicotine administered in adolescence, results in keeping with earlier findings of persistent desensitization. Our results indicate that prenatal nicotine exposure alters parameters of 5HT synaptic communication lasting into adolescence and changes the response to nicotine administration and withdrawal in adolescence, actions which may contribute to a subpopulation especially vulnerable to nicotine dependence.

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“…Nicotinic agonists decrease glutamate-and NMDA-induced neuronal death in cortical and hippocampal neurons in culture (Akaike et al, 1994;Donnelly-Roberts et al, 1996;Semba et al, 1996;Kaneko et al, 1997;Carlson et al, 1998;O'Neill et al, 1998;Prendergast et al, 2001b) (Table 1). Nicotine is also effective in protecting cortical neurons from cell death in vivo as a result of excitotoxic or ischemic lesion (Borlongan et al, 1995;O'Neill et al, 1998;Shimohama et al, 1998), although one study showed increased neuronal loss due to middle cerebral artery occlusion following chronic administration of nicotine through an osmotic minipump (Wang et al, 1997). Finally, nicotinic agonists can rescue cortical neuronal loss induced by nucleus basalis lesion in both young (Sjak-Shie and Meyer, 1993;Socci and Arendash, 1996;Nanri et al, 1997;Meyer et al, 1998b) and aged rats (Socci and Arendash, 1996).…”

Section: Neuronal Nachrs and Neuroprotectionmentioning

confidence: 99%

“…ceptors of the ␣-bungarotoxin-sensitive subfamily (␣7 subunit-containing) of nAChRs (Donnelly-Roberts et al, 1996;Kaneko et al, 1997;Kihara et al, 1997;Carlson et al, 1998;Shimohama et al, 1998;DajasBailador et al, 2000). However, in many cases, the neuroprotective effects of nicotine can be blocked by mecamylamine or dihydro-␤-erythroidine, antagonists relatively selective for the high-affinity subfamily (mainly ␣4/␤2 subunit-containing) of nAChRs (Kaneko et al, 1997;Zamani et al, 1997;Kihara et al, 1998;Ryan et al, 2001;Laudenbach et al, 2002).…”

Section: And In Vivomentioning

confidence: 99%

Nicotinic receptors in aging and dementia

2002

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Activation of neuronal nicotinic acetylcholine receptors (nAChRs) has been shown to maintain cognitive function following aging or the development of dementia. Nicotine and nicotinic agonists have been shown to improve cognitive function in aged or impaired subjects. Smoking has also been shown in some epidemiological studies to be protective against the development of neurodegenerative diseases. This is supported by animal studies that have shown nicotine to be neuroprotective both in vivo and in vitro. Treatment with nicotinic agonists may therefore be useful in both slowing the progression of neurodegenerative illnesses, and improving function in patients with the disease. While increased nicotinic function has been shown to be beneficial, loss of cholinergic markers is often seen in patients with dementia, suggesting that decreased cholinergic function could contribute to both the cognitive deficits, and perhaps the neuronal degeneration, associated with dementia. In this article we will review the literature on each of these areas. We will also present hypotheses that might address the mechanisms underlying the ability of nAChR function to protect against neurodegeneration or improve cognition, two potentially distinct actions of nicotine.

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Nicotinic α7 receptors protect against glutamate neurotoxicity and neuronal ischemic damage

Cited by 126 publications

References 12 publications

Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation

Roles of Nicotinic Receptors in Acetylcholinesterase Inhibitor-Induced Neuroprotection and Nicotinic Receptor Up-Regulation

Prenatal Nicotine Exposure Alters the Responses to Subsequent Nicotine Administration and Withdrawal in Adolescence: Serotonin Receptors and Cell Signaling

Nicotinic receptors in aging and dementia

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