2024-
2025
TRANSLATIONAL NEUROSCIENCE EXAM 3
MINOR 16 – TRANSLATIONAL NEUROSCIENCE
CHRISSY VAN BREUGEL
,INHOUDSOPGAVE
Translational neuroscience exam 3 ................................................................................................ 2
Why Translational Models Are Needed in Neuroscience Research ....................................................... 2
Alzheimer’s disease ...................................................................................................................... 4
Insights into Alzheimer’s Disease (AD) ............................................................................................... 4
Tau hypothesis ................................................................................................................................. 4
Dominant Gamma-secretase ............................................................................................................ 5
Sporadic Alzheimer's ........................................................................................................................ 5
Amyloid cascade hypothesis ............................................................................................................. 5
The cholinergic hypothesis fo Alzheimer's disease .............................................................................. 6
Vascular hypothesis of AD ................................................................................................................. 6
Amyloid angiopathy........................................................................................................................... 7
Neurodegenerative Diseases (NDDs) ............................................................................................. 7
Etiology ............................................................................................................................................ 8
Convergence to common pathways ................................................................................................... 8
Designing Experiments Using Model Systems ..................................................................................... 9
Myotonic Dystrophy ...................................................................................................................... 9
Targets for therapeutic strategies ..................................................................................................... 10
DM1 ............................................................................................................................................... 11
therapies ........................................................................................................................................ 13
Strategies ....................................................................................................................................... 13
SYMPTOMATIC TREATMENT DM1 ..................................................................................................... 14
Parkinson’s Disease (PD) ............................................................................................................. 15
Functional Anatomy of the Basal Ganglia in PD ................................................................................. 15
PARKINSON PATHOLOGY ............................................................................................................... 16
Direct Pathway (Facilitates Movement) ............................................................................................ 17
Normal Oscillatory Activity in the Basal Ganglia ................................................................................ 17
Abnormal Oscillations in Parkinson’s Disease .................................................................................. 18
Oscillation Mechanisms in Parkinson’s Disease ............................................................................... 18
Lewy bodies as a death mark of dopaminergic neurons ..................................................................... 19
therapies ........................................................................................................................................ 19
, TRANSLATIONAL NEUROSCIENCE EXAM 3
WHY TRANSLATIONAL MODELS ARE NEEDED IN NEUROSCIENCE RESEARCH
Translational models bridge the gap between basic neuroscience and clinical applications. These models
are essential for:
- Understanding complex brain disorders in a controlled environment.
- Testing hypotheses that cannot be studied directly in humans due to ethical or technical
limitations.
- Developing, validating, and optimizing therapeutic interventions.
- Exploring disease mechanisms in ways that align with human pathology.
Types of Translational Models and Their Pros and Cons
1. Animal Models
- They are living organisms with functional brains with different cell types
- Behavioral assays are available to study
- Genetic tools to study disease genes
o Ethical concerns
o Expensive and labor intensive
o Not human/patient specific
o KO ≠ mutation
o Difficult to model multifactorial disorders
2. In Vitro Models (e.g., organoids, neuronal cultures)
- Patient-specific
- Relevant cell-types
- 3D culture
o More labor-intensive
o No systemic connection
3. Immortalized cell lines
- No availability restriction
- Easy to manipulate
o Cell tipe is not related
o Translational value questionable
4. Patient-Derived Models (e.g., iPSC-derived neurons)
- Patient-specific material
- Relevant cell-type
o Limited availability
o 2D culture
5. Patient material
- Patient specific material
o Limited availability
o Cell type is not related
2025
TRANSLATIONAL NEUROSCIENCE EXAM 3
MINOR 16 – TRANSLATIONAL NEUROSCIENCE
CHRISSY VAN BREUGEL
,INHOUDSOPGAVE
Translational neuroscience exam 3 ................................................................................................ 2
Why Translational Models Are Needed in Neuroscience Research ....................................................... 2
Alzheimer’s disease ...................................................................................................................... 4
Insights into Alzheimer’s Disease (AD) ............................................................................................... 4
Tau hypothesis ................................................................................................................................. 4
Dominant Gamma-secretase ............................................................................................................ 5
Sporadic Alzheimer's ........................................................................................................................ 5
Amyloid cascade hypothesis ............................................................................................................. 5
The cholinergic hypothesis fo Alzheimer's disease .............................................................................. 6
Vascular hypothesis of AD ................................................................................................................. 6
Amyloid angiopathy........................................................................................................................... 7
Neurodegenerative Diseases (NDDs) ............................................................................................. 7
Etiology ............................................................................................................................................ 8
Convergence to common pathways ................................................................................................... 8
Designing Experiments Using Model Systems ..................................................................................... 9
Myotonic Dystrophy ...................................................................................................................... 9
Targets for therapeutic strategies ..................................................................................................... 10
DM1 ............................................................................................................................................... 11
therapies ........................................................................................................................................ 13
Strategies ....................................................................................................................................... 13
SYMPTOMATIC TREATMENT DM1 ..................................................................................................... 14
Parkinson’s Disease (PD) ............................................................................................................. 15
Functional Anatomy of the Basal Ganglia in PD ................................................................................. 15
PARKINSON PATHOLOGY ............................................................................................................... 16
Direct Pathway (Facilitates Movement) ............................................................................................ 17
Normal Oscillatory Activity in the Basal Ganglia ................................................................................ 17
Abnormal Oscillations in Parkinson’s Disease .................................................................................. 18
Oscillation Mechanisms in Parkinson’s Disease ............................................................................... 18
Lewy bodies as a death mark of dopaminergic neurons ..................................................................... 19
therapies ........................................................................................................................................ 19
, TRANSLATIONAL NEUROSCIENCE EXAM 3
WHY TRANSLATIONAL MODELS ARE NEEDED IN NEUROSCIENCE RESEARCH
Translational models bridge the gap between basic neuroscience and clinical applications. These models
are essential for:
- Understanding complex brain disorders in a controlled environment.
- Testing hypotheses that cannot be studied directly in humans due to ethical or technical
limitations.
- Developing, validating, and optimizing therapeutic interventions.
- Exploring disease mechanisms in ways that align with human pathology.
Types of Translational Models and Their Pros and Cons
1. Animal Models
- They are living organisms with functional brains with different cell types
- Behavioral assays are available to study
- Genetic tools to study disease genes
o Ethical concerns
o Expensive and labor intensive
o Not human/patient specific
o KO ≠ mutation
o Difficult to model multifactorial disorders
2. In Vitro Models (e.g., organoids, neuronal cultures)
- Patient-specific
- Relevant cell-types
- 3D culture
o More labor-intensive
o No systemic connection
3. Immortalized cell lines
- No availability restriction
- Easy to manipulate
o Cell tipe is not related
o Translational value questionable
4. Patient-Derived Models (e.g., iPSC-derived neurons)
- Patient-specific material
- Relevant cell-type
o Limited availability
o 2D culture
5. Patient material
- Patient specific material
o Limited availability
o Cell type is not related
