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Summary Minor Translational Neuroscience Part 1 - year 3 Biomedical Sciences/Medicine

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All the learning material from the elective seminar Translational neuroscience (year 3, Biomedical Sciences/Medicine) summarized using the learning objectives and concepts and explained with illustrations. Contains all information from lectures, self study, working groups and practicals.

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SUMMARY MINOR TRANSLATIONAL
NEUROSCIENCE PART 1
Elective minor year 3 – Biomedical Sciences




Radboud University, Nijmegen
Made by: Georgia Graat

,Basic concepts

Mental illnesses are not only a personal, but also an economic disaster. Among the top 10 causes of
disability across the world, 5 are related to mental illness (depression, alcohol use, schizophrenia,
bipolar and Alzheimer/dementia). Our aging society may change the ranking and cause dementia to
rise immensely in the ranking, also bringing many more costs.

The dilemma of
neuroscience is: how can we
improve our understanding
of the brain and treat or
prevent neurological
disorders in the future? The
two main sources for
information are fundamental
and clinical research. Fundamental research depends on animal models. The most efficient research
in this area is invasive, and we can use genetic modifications. The experiments are however harmful
or fatal. Clinical research relies on human subjects. There is a very limited set of methodologies
applicable, and it depends on results from basic research. The study groups are however very
heterogeneous. We can link these two types by translational research. To do this, you must think of
to which extent human and animal physiology is compatible, how to mimic human neurological
disorders in animal models (how do you give animals the same diseases without knowing what they
feel, only look at symptoms) and how to link molecular and cognitive aspects (how to check in
animals which cognitive changes happen).

The neuroscience field has evolved immensely over the years. There are several things currently
under investigation to how making those new techniques possible.

- Targeted genetic editing of animals → implement gene defects that you find in humans
exactly into the animal
- Targeted manipulation of memory and behavior → by electro stimulation or high levels of
voltage you can change the memory and behavior of animals
- Growing human neuronal networks in the dish → blood to induced potent stem cells and
make neuronal cells of them. Resembles patients specific background genetics
- Human brain organoids → resemble early brain development. To some extent in petri dish it
looks like a real brain

The gaps in neuroscience research that are present can be filled in over the years by the many
approaches of techniques we have available: anatomy and structural imaging, molecular biology and
biochemistry, genetics, electrophysiology, behavioral studies, functional imaging, computational
neuroscience and artificial intelligence.




Made by: Georgia Graat

, Neurological diseases

Alzheimer’s disease

Dementia is very common in people >70 years of age. Alzheimer’s disease makes up 70% of all these
cases. Other types are vascular dementia in 16% of the cases, and other types (frontotemporal,
Huntington, Lewy bodies and Wernicke-Korsakoff) in 14%. AD is prevalent in 5% of the population at
65-75 years, 20% in people 80-90 years of age and 35% in people >90 years. This is pure AD together
with mixed AD (Alzheimer with another type). Mixed dementia is much more common at higher
ages, as the whole brain starts to degenerate. The lifetime prevalence of AD is actually higher in
women, which has several reasons:

- Women live longer than men
o This explains the great lifetime incidence, but not
the greater prevalence per age group
- Cardiovascular disease is often underdiagnosed in women
o This can lead to AD due to neurodegeneration
- Female sex hormones play a role in the etiology of the
disease
- Differences in men and women in genes that are associated
with AD
- Differences in lifestyle of men and women
- Previous generations of women had lower education than
men
o This is a risk factor for developing AD due to lower neuronal connections

Currently 5.8 million people worldwide have
dementia, which is expected to rise every year to a
number of 13.8 million in 2050. There is a clear
projected growth in prevalence of this
neurodegenerative disease, mainly expected in low
and middle income countries. We see that the
maximum prevalence in high income countries is
reached and that there is a stabilization. Low and
middle income countries however show increasing prevalence. There are several reasons to describe
this phenomenon:

- Lifestyle
o High income countries have a healthy, good lifestyle that has improved over past
decades
o Low and middle income countries are declining in lifestyle or only starting to
improve, meaning they are exposed to much more risk factors
- Cardio-metabolic disease (diabetes and hypertension)
o High income countries have a good management of these
o Low and middle income countries have an increase in prevalence and suboptimal
management of these
- Education
o High income countries have more people with high education
o Low and middle income countries have a higher prevalence of illiteracy, which is a
risk factor



Made by: Georgia Graat

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Written in
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