Nicotine exposure reduces N-methyl-D-aspartate toxicity in the hippocampus: relation to distribution of the α7 nicotinic acetylcholine receptor subunit
Mark A. Prendergast, Barton R. Harris, Sveta Mayer, Robert C. Holley, James R. Pauly, John M. LittletonMed Sci Monit 2001; 7(6): BR1153-1160 :: ID: 507819
Abstract
Background: Exposure to nicotine has been shown to promote neuronal survival after excitotoxic insult to the brain. The role of specific nicotinic acetylcholine receptors (nAChRs) subtypes in mediating this effect is not well understood, however. Examination of distinct receptor subtypes in promoting neuronal survival is of importance not only in understanding the regulation of necrotic cell death but potentially in the development of novel pharmacological therapies that may reduce this form of neurodegeneration.
Material and methods: The present studies examined the relationship between distribution of α7 subunit-bearing nAChRs, using autoradiographic imaging of [125I]α-bungarotoxin binding, and protective effects of nicotine against excitotoxic damage. Organotypic cultures of rat hippocampus were exposed to N-methyl-D-aspartate (NMDA; 200 μM) for 1 hour with or without (–)-nicotine (0.1-10 μM) and the α7 nAChR antagonist methyllycaconitine (MLA; 100 nM). Neuronal damage was assayed 24 hours later by observation of uptake of the non-vital fluorescent marker propidium iodide.
Results: NMDA exposure produced significant neurotoxicity, particularly in pyramidal cell layers of CA3 and CA1, that was prevented by co-exposure to MK-801 (10 μM). Localization of the α7 subunit was varied with no binding observed in the dentate gyrus, low density in the CA3 and CA1 regions, and dense binding in the hilus. In all regions, co-exposure to (–)-nicotine (0.1-10.0 mM) significantly reduced (>30%) the cytotoxic consequences of NMDA insult. This protective effect was inhibited by co-exposure to MLA in the dentate and CA3, and to a lesser extent, CA1 regions.
Conclusion: The neuroprotective effect of nicotine against excitotoxicity, then, is not directly related to α7 subunit localization in the hippocampus.
Keywords: Acetylcholine, Glutamate, neuroprotection, NMDA, bungarotoxin, Hippocampus
Editorial
01 May 2024 : Editorial
Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) – Lifileucel (Amtagvi)DOI: 10.12659/MSM.944927
Med Sci Monit 2024; 30:e944927
In Press
07 May 2024 : Clinical Research
Treatment of AVN-Induced Proximal Pole Scaphoid Nonunion Using a Fifth and Fourth Extensor Compartmental Ar...Med Sci Monit In Press; DOI: 10.12659/MSM.944553
16 Mar 2024 : Clinical Research
Diagnostic Efficiency of ACR-TIRADS Score for Differentiating Benign and Malignant Thyroid Nodules of Vario...Med Sci Monit In Press; DOI: 10.12659/MSM.943228
08 May 2024 : Clinical Research
Effect of Individualized PEEP Guided by Driving Pressure on Diaphragm Function in Patients Undergoing Lapar...Med Sci Monit In Press; DOI: 10.12659/MSM.944022
21 Mar 2024 : Clinical Research
Impact of Serum Vitamin D, B6, and B12 and Cognitive Functions on Quality of Life in Peri- and Postmenopaus...Med Sci Monit In Press; DOI: 10.12659/MSM.943249
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952