Cholinergic neurodegeneration in an Alzheimer mouse model overexpressing amyloid-precursor protein with the Swedish-Dutch-Iowa mutations
| Autor: | Bianca Hutter-Schmid, Christian Humpel, Bettina M. Foidl, Harald R. Bliem, Patricia Do-Dinh |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Cognitive Neuroscience Experimental and Cognitive Psychology Mice Transgenic Plaque Amyloid Anxiety Nucleus basalis Article 03 medical and health sciences Behavioral Neuroscience Amyloid beta-Protein Precursor Mice 0302 clinical medicine Alzheimer Disease medicine Amyloid precursor protein Animals Cholinergic neuron Cerebral Cortex biology Behavior Animal business.industry Neurodegeneration medicine.disease Choline acetyltransferase Cholinergic Neurons Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Cerebral cortex Basal Nucleus of Meynert biology.protein Cholinergic business Neuroscience 030217 neurology & neurosurgery |
| Popis: | Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is mainly characterized by beta-amyloid (Aβ) plaque deposition, Tau pathology and dysfunction of the cholinergic system causing memory impairment. The aim of the present study was to examine (1) anxiety and cognition, (2) Aβ plaque deposition and (3) degeneration of cholinergic neurons in the nucleus basalis of Meynert (nbM) and cortical cholinergic innervation in an Alzheimer mouse model (APP_SweDI; overexpressing amyloid precursor protein (APP) with the Swedish K670N/M671L, Dutch E693Q, and Iowa D694N mutations). Our results show that 12-month-old APP_SweDI mice were more anxious and had more memory impairment. A large number of Aβ plaques were already visible at the age of 6 months and increased with age. A significant decrease in cholinergic neurons was seen in the transgenic mouse model in comparison to the wild-type mice, identified by immunohistochemistry against choline acetyltransferase (ChAT) and p75 neurotrophin receptor as well as by in situ hybridization. Moreover, a significant decrease in cortical cholinergic fiber density was found in the transgenic mice as compared to the wild-type. In the cerebral cortex of APP_SweDI mice, swollen cholinergic varicosities were seen in the vicinity of Aβ plaques. In conclusion, the present study shows that in an AD mouse model (APP_SweDI mice) a high Aβ plaque load in the cortex causes damage to cholinergic axons in the cortex, followed by subsequent retrograde-induced cell death of cholinergic neurons and some forms of compensatory processes. This degeneration was accompanied by enhanced anxiety and impaired cognition. |
| Databáze: | OpenAIRE |
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