MP60-10 LOCAL PHARMACOLOGICAL REGULATORY CHANGES IN ISOLATED BLADDERS OF ALZHEIMER MICE

Autor: Gommert van Koeveringe, Celine Meriaux, Aryo Zare, Ramona Hohnen, Mohammad S. Rahnama'i
Rok vydání: 2016
Předmět:
Zdroj: Journal of Urology. 195
ISSN: 1527-3792
0022-5347
DOI: 10.1016/j.juro.2016.02.863
Popis: INTRODUCTION AND OBJECTIVES: Autonomic dysfunction in Alzheimer0s disease (AD) results in incontinence and voiding dysfunction. So far these dysfunctions have been attributed to either cognitive decline or damage to micturition control centers in the central nervous system. Pharmacological therapy for AD often involves cholinergic agonists whereas overactive bladder symptoms need a counteracting drug treatment. To solve this therapeutic dilemma, specific knowledge on local bladder regulatory systems is necessary. In this study, we investigated the effect of muscarinic stimulation and complete depolarisation on bladders from transgenic AD mice, as well as the presence of amyloid-b aggregation within the bladder wall. METHODS: Bladders of 16 transgenic AD mice of the APP/ PS1 model and nine wild type (WT) mice were dissected. Twelve AD and seven WT bladders were catheterized transurethrally and placed in an organ bath containing carboxygenated physiological solution. After filling of the bladder and stimulation with 1 mM of carbachol the organ bath was washed. Subsequently the bladder was stimulated with 0.1 M KCl. The area under the curve (AUC) was analysed from the beginning of the contraction until the maximum pressure after addition of either carbachol or KCl was reached. Indirect immunohistochemical staining was performed on four AD mice and two WT mice using a primary antibody against amyloid precursor protein (APP) and amyloidb and the appropriate secondary antibody. RESULTS: A lower frequency of asynchronized microcontractions was recorded during the baseline state in AD mice. The AUC is lower in AD mice compared to WT mice after KCl administration. The bladder muscular layer of WT mice showed no staining to APP or amyloid-b in contrast to AD mice. Immunoreactivity was detected in the urothelial and suburothelial layers in bladders of WT mice. In contrast, mild urothelial staining was present in bladders of WT mice. CONCLUSIONS: We hypothesize that in this model of Alzheimer0s disease a decrease of baseline microcontractile activity and of stimulated potassium depolarisation induced contractile activity are most probably related to amyloid-b induced alterations in neuromuscular membrane activity and more specifically the calcium or potassium channels at the bladder level.
Databáze: OpenAIRE
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