Evidence map›Paper›PMID 39936411›Full record

ArticleCurrent Alzheimer research2024

Age- and Genotype-Dependent Effects of Chronic Nicotine on Presenilin1/2 Double Knockout Mice: From Behavior to Molecular Pathways.

Youwen Si, Bo Meng, Feiyan Qi

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Article in Current Alzheimer research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Youwen SiKey Laboratory of Brain Functional Genomics, Ministry of Education, School of Life Sciences, East China Normal University, Shanghai, China.ORCID 0000-0003-3093-6355
Bo MengKey Laboratory of Brain Functional Genomics, Ministry of Education, School of Life Sciences, East China Normal University, Shanghai, China.ORCID 0000-0003-0433-5038
Feiyan QiJoint Institute of Tobacco and Health, Yunnan Academy of Tobacco Agricultural Science, Kunming, China.ORCID 0000-0002-0765-2162

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: The potential therapeutic role of nicotine in Alzheimer's disease (AD) remains controversial, particularly regarding its age-dependent effects and underlying mechanisms. Methods: This study investigated the impact of chronic nicotine administration on cognitive function and molecular pathways in Presenilin 1/2 double knockout (DKO) mice, an amyloid-β: (Aβ:)- independent model of AD. Three-month-old and eight-month-old DKO and wild-type (WT) mice received oral nicotine treatment (100 μg/ml) for three months. Behavioral assessments revealed that while the 6-month-old cohort showed no significant differences between nicotine-treated and control groups regardless of genotype, nicotine improved contextual fear memory in 11-month- old DKO mice but impaired nest-building ability and cued fear memory in age-matched WT controls. Transcriptome analysis of the prefrontal cortex identified distinct molecular responses to nicotine between genotypes. Results: In DKO mice, nicotine modulated neuropeptide signaling and reduced astrocyte activation, while in WT mice, it disrupted cytokine-cytokine receptor interaction and neuroactive ligand- receptor interaction pathways. Western blot analysis revealed that nicotine treatment significantly reduced tau hyperphosphorylation and Glial Fibrillary Acidic Protein (GFAP) expression in 11-month-old DKO mice, which was further confirmed by immunohistochemistry showing decreased astrocyte activation in multiple brain regions Conclusion: These findings demonstrate that nicotine's effects on cognition and molecular pathways are both age- and genotype-dependent, suggesting its therapeutic potential may be limited to specific stages of neurodegeneration while potentially having adverse effects in healthy aging brains.

Indexed as

AgingBehavior, AnimalNicotineNicotinic AgonistsPresenilin-1Presenilin-2Age FactorsAlzheimer DiseaseAnimalsDisease Models, AnimalFearGenotypeMaleMiceMice, Inbred C57BLMice, KnockoutNicotineNicotinic AgonistsPresenilin-1presenilin 1, mousePresenilin-2Psen2 protein, mouseAlzheimer`s diseasebehaviorgenotypes.nicotinePresenilinRNA sequencing

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.