Does Oxybutynin Alter Plaques, Amyloid Beta Peptides and Behavior in a Mouse Model of Alzheimer's Disease?

Adam P. Klausner, Seema Sharma, Sophie Fletcher, Pamela Neff, Sang Kuk Yang, Hwancheol Son, Jeremy B. Tuttle, William D. Steers

Research output: Contribution to journalArticle

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Abstract

Purpose: In elderly patients oxybutynin (Sigma-Aldrich) is commonly used to treat overactive bladder despite increased prevalence of Alzheimer's disease in this population. We determined whether oxybutynin altered plaque formation, amyloid β peptide expression and behavior in a transgenic mouse model of Alzheimer's disease expressing the mutant human presenilin 1 (DeltaE9) and a chimeric mouse/human amyloid precursor protein (APPswe). Materials and Methods: Mice were treated for 30 days in an acute experiment or 5 months in a chronic experiment with oxybutynin (30 mg/kg) or vehicle. Behavioral testing was performed monthly with the elevated plus maze (Med Associates, St. Albans, Vermont) in the chronic experiment. Brains were tested for plaque burden using Hirano silver and thioflavin-S (Sigma-Aldrich) staining. Amyloid β peptide expression was tested using enzyme-linked immunosorbent assay for amyloid β peptides 1-40 and 1-42. Results: Animals treated with chronic oxybutynin had a decreased plaque burden in the hippocampus (mean ± SEM 2.2 ± 0.4 vs 4.1 ± 0.9 plaques, p <0.05) and cortex (5.8 ± 0.7 vs 11.6 ± 2.1, p <0.05) compared to animals treated with vehicle. Oxybutynin treated animals also had decreased expression of amyloid β 1-42 (82.8 ± 9.0 ηg/ml vs 105.6 ± 5.5 ηg/ml, p = 0.05) compared to animals treated with vehicle. Female Alzheimer's disease mice treated with oxybutynin but not males showed improved behavior with a greater percent of time spent in the closed arm or elevated plus maze (95.9% ± 1.6% vs 35.6% ± 18.9%, p <0.05). The greatest difference was noted at 3 months of treatment compared to vehicle. Conclusions: These results suggest that oxybutynin may slow the progression of Alzheimer's disease in this model.

Original languageEnglish
Pages (from-to)1173-1177
Number of pages5
JournalJournal of Urology
Volume179
Issue number3
DOIs
StatePublished - 1 Mar 2008

Fingerprint

Amyloid beta-Peptides
Alzheimer Disease
Amyloid
Peptides
Overactive Urinary Bladder
Amyloid beta-Protein Precursor
Amyloid Plaques
oxybutynin
Silver
Transgenic Mice
Hippocampus
Enzyme-Linked Immunosorbent Assay
Staining and Labeling
Brain
Population

Keywords

  • Alzheimer disease
  • bladder
  • disease progression
  • mice
  • oxybutynin

Cite this

Klausner, Adam P. ; Sharma, Seema ; Fletcher, Sophie ; Neff, Pamela ; Yang, Sang Kuk ; Son, Hwancheol ; Tuttle, Jeremy B. ; Steers, William D. / Does Oxybutynin Alter Plaques, Amyloid Beta Peptides and Behavior in a Mouse Model of Alzheimer's Disease?. In: Journal of Urology. 2008 ; Vol. 179, No. 3. pp. 1173-1177.
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title = "Does Oxybutynin Alter Plaques, Amyloid Beta Peptides and Behavior in a Mouse Model of Alzheimer's Disease?",
abstract = "Purpose: In elderly patients oxybutynin (Sigma-Aldrich™) is commonly used to treat overactive bladder despite increased prevalence of Alzheimer's disease in this population. We determined whether oxybutynin altered plaque formation, amyloid β peptide expression and behavior in a transgenic mouse model of Alzheimer's disease expressing the mutant human presenilin 1 (DeltaE9) and a chimeric mouse/human amyloid precursor protein (APPswe). Materials and Methods: Mice were treated for 30 days in an acute experiment or 5 months in a chronic experiment with oxybutynin (30 mg/kg) or vehicle. Behavioral testing was performed monthly with the elevated plus maze (Med Associates, St. Albans, Vermont) in the chronic experiment. Brains were tested for plaque burden using Hirano silver and thioflavin-S (Sigma-Aldrich) staining. Amyloid β peptide expression was tested using enzyme-linked immunosorbent assay for amyloid β peptides 1-40 and 1-42. Results: Animals treated with chronic oxybutynin had a decreased plaque burden in the hippocampus (mean ± SEM 2.2 ± 0.4 vs 4.1 ± 0.9 plaques, p <0.05) and cortex (5.8 ± 0.7 vs 11.6 ± 2.1, p <0.05) compared to animals treated with vehicle. Oxybutynin treated animals also had decreased expression of amyloid β 1-42 (82.8 ± 9.0 ηg/ml vs 105.6 ± 5.5 ηg/ml, p = 0.05) compared to animals treated with vehicle. Female Alzheimer's disease mice treated with oxybutynin but not males showed improved behavior with a greater percent of time spent in the closed arm or elevated plus maze (95.9{\%} ± 1.6{\%} vs 35.6{\%} ± 18.9{\%}, p <0.05). The greatest difference was noted at 3 months of treatment compared to vehicle. Conclusions: These results suggest that oxybutynin may slow the progression of Alzheimer's disease in this model.",
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Klausner, AP, Sharma, S, Fletcher, S, Neff, P, Yang, SK, Son, H, Tuttle, JB & Steers, WD 2008, 'Does Oxybutynin Alter Plaques, Amyloid Beta Peptides and Behavior in a Mouse Model of Alzheimer's Disease?', Journal of Urology, vol. 179, no. 3, pp. 1173-1177. https://doi.org/10.1016/j.juro.2007.10.034

Does Oxybutynin Alter Plaques, Amyloid Beta Peptides and Behavior in a Mouse Model of Alzheimer's Disease? / Klausner, Adam P.; Sharma, Seema; Fletcher, Sophie; Neff, Pamela; Yang, Sang Kuk; Son, Hwancheol; Tuttle, Jeremy B.; Steers, William D.

In: Journal of Urology, Vol. 179, No. 3, 01.03.2008, p. 1173-1177.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Does Oxybutynin Alter Plaques, Amyloid Beta Peptides and Behavior in a Mouse Model of Alzheimer's Disease?

AU - Klausner, Adam P.

AU - Sharma, Seema

AU - Fletcher, Sophie

AU - Neff, Pamela

AU - Yang, Sang Kuk

AU - Son, Hwancheol

AU - Tuttle, Jeremy B.

AU - Steers, William D.

PY - 2008/3/1

Y1 - 2008/3/1

N2 - Purpose: In elderly patients oxybutynin (Sigma-Aldrich™) is commonly used to treat overactive bladder despite increased prevalence of Alzheimer's disease in this population. We determined whether oxybutynin altered plaque formation, amyloid β peptide expression and behavior in a transgenic mouse model of Alzheimer's disease expressing the mutant human presenilin 1 (DeltaE9) and a chimeric mouse/human amyloid precursor protein (APPswe). Materials and Methods: Mice were treated for 30 days in an acute experiment or 5 months in a chronic experiment with oxybutynin (30 mg/kg) or vehicle. Behavioral testing was performed monthly with the elevated plus maze (Med Associates, St. Albans, Vermont) in the chronic experiment. Brains were tested for plaque burden using Hirano silver and thioflavin-S (Sigma-Aldrich) staining. Amyloid β peptide expression was tested using enzyme-linked immunosorbent assay for amyloid β peptides 1-40 and 1-42. Results: Animals treated with chronic oxybutynin had a decreased plaque burden in the hippocampus (mean ± SEM 2.2 ± 0.4 vs 4.1 ± 0.9 plaques, p <0.05) and cortex (5.8 ± 0.7 vs 11.6 ± 2.1, p <0.05) compared to animals treated with vehicle. Oxybutynin treated animals also had decreased expression of amyloid β 1-42 (82.8 ± 9.0 ηg/ml vs 105.6 ± 5.5 ηg/ml, p = 0.05) compared to animals treated with vehicle. Female Alzheimer's disease mice treated with oxybutynin but not males showed improved behavior with a greater percent of time spent in the closed arm or elevated plus maze (95.9% ± 1.6% vs 35.6% ± 18.9%, p <0.05). The greatest difference was noted at 3 months of treatment compared to vehicle. Conclusions: These results suggest that oxybutynin may slow the progression of Alzheimer's disease in this model.

AB - Purpose: In elderly patients oxybutynin (Sigma-Aldrich™) is commonly used to treat overactive bladder despite increased prevalence of Alzheimer's disease in this population. We determined whether oxybutynin altered plaque formation, amyloid β peptide expression and behavior in a transgenic mouse model of Alzheimer's disease expressing the mutant human presenilin 1 (DeltaE9) and a chimeric mouse/human amyloid precursor protein (APPswe). Materials and Methods: Mice were treated for 30 days in an acute experiment or 5 months in a chronic experiment with oxybutynin (30 mg/kg) or vehicle. Behavioral testing was performed monthly with the elevated plus maze (Med Associates, St. Albans, Vermont) in the chronic experiment. Brains were tested for plaque burden using Hirano silver and thioflavin-S (Sigma-Aldrich) staining. Amyloid β peptide expression was tested using enzyme-linked immunosorbent assay for amyloid β peptides 1-40 and 1-42. Results: Animals treated with chronic oxybutynin had a decreased plaque burden in the hippocampus (mean ± SEM 2.2 ± 0.4 vs 4.1 ± 0.9 plaques, p <0.05) and cortex (5.8 ± 0.7 vs 11.6 ± 2.1, p <0.05) compared to animals treated with vehicle. Oxybutynin treated animals also had decreased expression of amyloid β 1-42 (82.8 ± 9.0 ηg/ml vs 105.6 ± 5.5 ηg/ml, p = 0.05) compared to animals treated with vehicle. Female Alzheimer's disease mice treated with oxybutynin but not males showed improved behavior with a greater percent of time spent in the closed arm or elevated plus maze (95.9% ± 1.6% vs 35.6% ± 18.9%, p <0.05). The greatest difference was noted at 3 months of treatment compared to vehicle. Conclusions: These results suggest that oxybutynin may slow the progression of Alzheimer's disease in this model.

KW - Alzheimer disease

KW - bladder

KW - disease progression

KW - mice

KW - oxybutynin

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