Neurobiology and Neurodegenerative Diseases
Focus:
I am planning to use this module in my advanced neurobiology course. Neurodegenerative diseases (including Alzheimer’s disease) is one of the topics that we discuss and I am planning this module for the segment in which we discuss the modifiers of the disease. These modifiers can be genetic and/or pharmacological.
This module is designed to discuss environmental enrichment as a modifier (suppressor) of Alzheimer’s disease in a mouse/rat model. This is an interesting modifier because it cannot be considered as an obvious genetic or pharmacological modifier and therefore allows for discussion on the types of modifiers. Also this provides an opportunity to discuss future studies to figure out the mechanism of the effect.
Different research groups analyzing the effects of environmental enrichment Abeta deposits as a marker for Alzheimers disease published the papers included in the module.
Overview:
Applicable for Courses:
NeurobiologyEducational Level:
Upper-levelsRoadmap Objectives:
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- Article: Environmental enrichment exacerbates amyloid plaque formation in a transgenic mouse model of Alzheimer’s disease. JL Jankowsky et al (2003) Journal of Neuropathology and Experimental Neurology Vol. 62 No 12 1220-1227
- Content area/major concepts: I chose this paper as the first paper in the module because it introduces all the key concepts and experimental paradigms.
The papers shows environmental enrichment increases amyloid beta plaque load in mice expressing mutant Amyloid precursor protein (APP). This finding is counter to their hypothesis (which was based on published literature).
A news media article can precede this paper. However, this paper is fairly simple and straightforward. This is one of the reasons for this paper as the first paper in the module.
Alzheimer’s disease (Memory/Hippocampus/Neurodegenerative disorders), Amyloid precursor protein (APP), A-beta, Transmembrane proteins, Proteases, Protein cleavage and processing - Methods or technology used to obtain data: Transgenic mice (disease model), Immunohistochemistry and ELISA, Biochemical techniques.
- How the CREATE strategy was used:
- Biggest teaching challenge: Concepts and jargon in genetics, pathogenic mutations, transgenic animal model
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- Article: Environmental enrichment reduces Aβ levels and Amyloid deposition in transgenic mice O Lazarov et al (2005) Cell Vol 120 701-713
- Content area/major concepts: This paper got opposite results i.e environmental enrichment decreased A-beta levels and other related markers of amyloid pathology. The authors discuss the reasons for the differences in their findings versus paper 1.
These two papers provide plenty of talking points to compare and contrast the findings and implication for the scientific method.
Transgenic mice and their genetic background, types of memory. Most of the concepts in paper 2 and 3 are same as paper 1). - Methods or technology used to obtain data: Transgenic mice, Immunohistochemistry, Western blot, ELISA, Biochemical analysis, and Microarray.
- How the CREATE strategy was used:
- Biggest teaching challenge:
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- Article: Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer’s disease JL Jankowsky et al (2005) The Journal of Neuroscience 25(21):5217-5227
- Content area/major concepts: This is a follow up study to paper 1. In this paper the authors extended their analysis to include behavioral effect of environmental enrichment in mice expressing mutant APP. They show that environmentally enriched APP mutant mice had improved cognition in spite of increased Aβ load. They discuss the reasons for the differences in their findings versus paper 2.
Transgenic mice and their genetic background, types of memory. Most of the concepts in paper 2 and 3 are same as paper 1) - Methods or technology used to obtain data: Behavioral testing for memory (Morris water maze, Radial water maze), Transgenic mice and their genetic background (disease model), Immunohistochemistry and ELISA, Biochemical techniques.
- How the CREATE strategy was used:
- Biggest teaching challenge: