ArticleFrontiers in aging neuroscience2014
Cotinine halts the advance of Alzheimer's disease-like pathology and associated depressive-like behavior in Tg6799 mice.
Article in Frontiers in aging neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Association between serum cotinine levels and cognitive function in Americans aged 60 and older: A cross-sectional study.Medicine · 2026Article
- Adult-onset hippocampal α7 nicotinic acetylcholine receptor loss rapidly drives Alzheimer-like neuropathology in mice.Frontiers in pharmacology · 2026Article
- Qifuyin alleviates anxiety and depression in 3×Tg-AD mice by modulating neuroendocrine function.Frontiers in psychiatry · 2025Article
- Effects of social dominance and acute social stress on morphology of microglia and structural integrity of the medial prefrontal cortex.Brain, behavior, and immunity · 2024Article
- Can Small Molecules Provide Clues on Disease Progression in Cerebrospinal Fluid from Mild Cognitive Impairment and Alzheimer's Disease Patients?Environmental science & technology · 2024Article
- The neural basis of neuropsychiatric symptoms in Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- Discovery of drug lead compounds for Anti-Alzheimer's disease on the basis of synaptic plasticity.Heliyon · 2023Article
- Nicotinic acetylcholine receptors and learning and memory deficits in Neuroinflammatory diseases.Frontiers in neuroscience · 2023Review
- Developmental impaired Akt signaling in the Shank1 and Shank3 double knock-out mice.Molecular psychiatry · 2021Article
- Self-Administration of Cotinine in Wistar Rats: Comparisons to Nicotine.The Journal of pharmacology and experimental therapeutics · 2021Article
- Anxiolytic, Promnesic, Anti-Acetylcholinesterase and Antioxidant Effects of Cotinine and 6-Hydroxy-L-Nicotine in Scopolamine-Induced Zebrafish (Antioxidants (Basel, Switzerland) · 2021Article
- Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions.Frontiers in behavioral neuroscience · 2021Review
- Cholinergic Receptor Modulation as a Target for Preventing Dementia in Parkinson's Disease.Frontiers in neuroscience · 2021Review
- Cotinine and 6-Hydroxy-L-Nicotine Reverses Memory Deficits and Reduces Oxidative Stress in AβAntioxidants (Basel, Switzerland) · 2020Article
- Strategies for the Treatment of Parkinson's Disease: Beyond Dopamine.Frontiers in aging neuroscience · 2020Article
- Intranasal Cotinine Plus Krill Oil Facilitates Fear Extinction, Decreases Depressive-Like Behavior, and Increases Hippocampal Calcineurin A Levels in Mice.Molecular neurobiology · 2018Article
- Cotinine: A Therapy for Memory Extinction in Post-traumatic Stress Disorder.Molecular neurobiology · 2018Review
- Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review.Frontiers in neuroscience · 2018Article
- Cotinine administration improves impaired cognition in the mouse model of Fragile X syndrome.The European journal of neuroscience · 2017Article
- Nicotinic ligands as multifunctional agents for the treatment of neuropsychiatric disorders.Biochemical pharmacology · 2015Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-β (Aβ) plaque pathology in transgenic 6799 mice (Tg6799 mice) when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in Tg6799 mice when left untreated until after a more advanced stage of the disease's development. The results show that vehicle-treated Tg6799 mice displayed an accentuated loss of working memory and an abundant Aβ plaque pathology that were accompanied by higher levels of depressive-like behavior as compared to control littermates. By contrast, prolonged daily cotinine treatment to Tg6799 mice, withheld until after a mid-level progression of AD-like pathology, reduced Aβ levels/plaques and depressive-like behavior. Moreover, this treatment paradigm dramatically improved working memory as compared to control littermates. The beneficial effects of cotinine were accompanied by an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices of Tg6799 mice. This suggests that cotinine halts the progression of AD-like pathology while reducing depressive-like behavior by stimulating signaling pathways supporting synaptic plasticity in Tg6799 mice. The potential use of cotinine to treat cognitive and non-cognitive symptoms of AD is discussed.
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