MilliporeSigma
  • Home
  • Search Results
  • Modulation of neuronal nicotinic receptor by quinolizidine alkaloids causes neuroprotection on a cellular Alzheimer model.

Modulation of neuronal nicotinic receptor by quinolizidine alkaloids causes neuroprotection on a cellular Alzheimer model.

Journal of Alzheimer's disease : JAD (2014-05-16)
Juan A Araya, Alejandra E Ramírez, Daniela Figueroa-Aroca, Gastón J Sotes, Claudia Pérez, Jose Becerra, Francisco Saez-Orellana, Leonardo Guzmán, Luis G Aguayo, Jorge Fuentealba
ABSTRACT

Alzheimer's disease (AD) is a progressive and neurodegenerative disorder and one of the current therapies involves strengthening the cholinergic tone in central synapses. Neuroprotective properties for nicotine have been described in AD, through its actions on nicotinic receptors and the further activation of the PI3K/Akt/Bcl-2 survival pathway. We have tested a quinolizidine alkaloid extract (TM0112) obtained from Teline monspessulanna (L.) K. Koch seeds to evaluate its action on nicotinic acetylcholine receptor (nAChR) in a neuronal AD model. Our data show that PC-12 cells pretreated with amyloid-β (Aβ) peptide for 24 h in presence of TM0112 modified Aβ-reduction on cellular viability (Aβ = 80 ± 3%; +TM0112 = 113 ± 4%, n = 15). In addition, this effect was blocked with atropine, MLA, and α-BTX (+TM0112+atropine = 87 ± 4%; +TM0112+MLA = 86 ± 4%; +TM0112+α-BTX = 92 ± 3%). Furthermore, similar protective effects were observed in rat cortical neurons (Aβ = 63 ± 6%; +TM0112 = 114 ± 8%), but not in HEK293T cells (Aβ = 61.4 ± 6.1%; +TM0112 = 62.8 ± 5.2) that do not express α7 nAChR. Moreover, the frequency of synaptic activity in the neuronal network (Aβ = 51.6 ± 16.9%; +TM0112 = 210.8 ± 47.9%, n > 10), as well as the intracellular Ca2+ transients were recovered by TM0112 (Aβ = 61.4 ± 6.9%; +TM0112 = 112.0 ± 5.7%; n = 3) in rat hippocampal neurons. TM0112 increased P-Akt, up to 250% with respect to control, and elevated Bcl-2/Bax percentage (Aβ = 61.0 ± 8.2%; +TM0112 = 105.4 ± 19.5%, n = 4), suggesting a coupling between nAChR activation and an intracellular neuroprotective pathway. Our results suggest that TM0112 could be a new potential source for anti-AD drugs.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-SV2A antibody produced in goat, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-MAP2 (2a+2b) antibody, Mouse monoclonal, ~2 mg/mL, clone AP-20, purified from hybridoma cell culture
Sigma-Aldrich
Anti-Bcl-2 (ab1) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-MAP2 (2a+2b) antibody, Mouse monoclonal, clone AP-20, ascites fluid
Sigma-Aldrich
Calcein, Used for the fluorometric determination of calcium and EDTA titration of calcium in the presence of magnesium.
SAFC
L-Glutamine
Sigma-Aldrich
Ethidium homodimer, suitable for fluorescence, ~90% (HPCE)
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
Anti-SV2A antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Monoclonal Anti-MAP2 antibody produced in mouse, clone HM-2, ascites fluid
Sigma-Aldrich
Monoclonal Anti-Bcl-2 antibody produced in mouse, clone Bcl-2-100, ascites fluid
Sigma-Aldrich
Anti-MAP2 antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-MAP2 antibody produced in rabbit, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-MAP2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
L-Glutamine
Supelco
L-Glutamine, certified reference material, TraceCERT®
Sigma-Aldrich
Anti-SV2A antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-BCL2 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-BCL2 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-MAP2 antibody, Mouse Monoclonal, clone HM-2, purified from hybridoma cell culture
Supelco
L-Glutamine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Anti-MAP2 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-BCL2 (Ab-70) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-BCL2 (Ab-56) antibody produced in rabbit, affinity isolated antibody