This is the final project for the course neurobiology of brain and behaviour. This consists analysis of the neurodegenerative disease- Amyotrophic lateral sclerosis (ASL)

1. By SAKSHI PALOD
UNDERSTANDING
THE BRAIN:
NEUROBIOLOGY OF
EVERYDAY LIFE

2. INTRODUCTION
• I have chosen the case of Dr. Stephen
hawking for my project, who was a British
theoretical physicist, cosmologist, and
author who made significant contributions
to the fields of theoretical physics and
cosmology. He was diagnosed with
Amyotrophic lateral sclerosis at the age of
21. He is someone who I personally find
inspiring and with his birthday nearing I
thought he would be a perfect example.

3. • ALS is a fatal motor neuron disease for
which there is no cure present. It’s
characterized by progressive
degeneration of nerve cells in the spinal
cord and the brain. ALS affects voluntary
control of arms and legs. As more and
more nerve cells die ALS spreads to
other parts of the body, which eventually
affects speaking, swallowing, chewing
and breathing. ALS has no effect on a
person’s senses and intelligence.
AMYOTROPHIC LATERAL
SCLEROSIS (ALS)
-A fatal neurodegenerative disorder

4. 1. Muscle Weakness
2. Muscle twitching
3.Difficulty speaking (dysarthria)
4.Difficulty swallowing (dysphagia)
5.Muscle cramps and stiffness
6. Progressive paralysis
7. Respiratory problems
ALS SYMPTOMS

5. MULTIPLE
SCELORIS VS ALS

6. MOTOR NEURONS
Motor neurons are a type of nerve cell responsible for
transmitting signals from the central nervous system
(CNS), specifically the brain and spinal cord, to muscles
and glands throughout the body.
We know that there are motor units which innervates muscle
fibers to control movement. And the communication between
motor neuron and muscle fiber is made possible because of
neurotransmistter acetylcholine through neuromuscular
junction
The neurotransmitter acetylcholine binds to receptors on the
muscle fiber's membrane, and leads to muscle contraction
For control over voluntary movements motor
neurons are important. So perfect functioning of
motor neuron is very essential

7. - The cause of the ALS is unknown
but we understand the altered
processes in people with ALS
-ALS is characterized by the loss
of both upper and lower motor
neurons
-motor neurons are crucial nerve
cells that send signals from the
brain to the muscles throughout
the body to control voluntary
movements
- As the motor neurons stop
sending signals, the muscles
weakens leading to paralysis

8. Many
different
aspects of
motor
neuron
function
are
affected in
ALS
1. Problems with protein
Proteins that are not
transported to cell body
accumulate in cytoplasm
It is found that errors in
systems that makes proteins
result in creation of proteins
with abnormal shape and
leads to aggregation of
protein.
2. DNA repair processes
The proteins become toxic and
cause damage to mitochondria
which can lead to breaks in the
DNA of the cell
ALS affects the DNA repair
processes and when DNA breaks,
they are poorly repaired which
ultimately leads to the death of
the neuron
3. Transport defects
ALS affected neurons often
have problems
transforming RNA, proteins
and vesicles
If neurotransmitters cannot
be moved along the axon
and if they can’t get
released from the neuron.
The neuron can’t send
messages to its target cells.
Alfredo Torres
Laboratory
manager
4. Cytoskeletal defects
Damage to cytoskeleton
can cause axon to
retract and axon loses
its connection to the
muscle nearby. It can no
longer signal the muscle
to contract

9. We’ve studied that neurons don’t exist on
their own and they need glia cells
Astrocytes and oligodendrocytes are two
essential non-neural cells that play roles in
supporting and maintaining the function of
neurons in the central nervous system (CNS).
Astrocytes are responsible for keeping the
environment clean whereas oligodendrocytes
are important in myelination and axonal
support
other cells

10. 01 02
GLIAL CELLS
03
Oligodendrocytes in ASL
Oligodendrocytes in people
with ASL are dysfunctional
Astrocytes in ASL
There is reduced uptake of
neurotransmitters which leads
to over activation of the
receptors at synapse, resulting
in death of neuron
Astrocytes and microglia can
produce factors that protect
or damage motor neurons.
Neuronal death occurs when
excessive damaging factors
are produced

11. EXCITOTOXITY
Astrocytes, which are glial cells in the central
nervous system, play a key role in clearing excess
glutamate from the synaptic cleft. In ALS,
dysfunction of astrocytes may compromise their
ability to efficiently clear glutamate.
This extra glutamate overstimulates the receptors
and prolonged excitotoxity leads to the death of
neuron.

12. RESPIRATORY ISSUES IN ALS
The lower motor neurons, which extend from the spinal
cord to the muscles, control the muscles involved in
breathing, such as the diaphragm and intercostal
muscles.
The muscles important for breathing like the diaphragm, throat
muscles and abdominal muscles are innervated by motor
neurons. There’s a collection of neurons which come up with
the breathing patterns with the help from structures in the
brain like medulla
The diaphragm, the primary muscle responsible for initiating the
breathing process, may weaken due to the loss of motor neurons.
People with ALS need breathing assistance and Unfortunately
the most common cause of death for people with ALS is
breathing failure.

13. COMMUNICATION FAILURE
• ALS leads to speech impairment as it
also affects the muscles required in
speaking
• We’ve seen that, problems in many
brain areas like brocas’s area or
wernicke’s area can lead to problems
in communication. But none is the
case here.
• It is The weakening of tongue, jaw,
and facial muscles that hampers
articulation, causing slurred and
difficult-to-understand speech, a
condition known as dysarthria.

14. Stephen hawking despite having this debilitating condition continued to live on for
decades and was one of the most profound scientists in his field of study. How so?
• ALS primarily targets motor neurons, which transmit signals to muscles for
movement. The ability to feel touch, pain, temperature, pressure etc is
governed by sensory neurons. Thus sensory functions are preserved in ALS
patients
• ALS also leaves the cognitive function relatively intact. Memory, reasoning, and
other cognitive abilities are typically preserved, distinguishing ALS from other
neurodegenerative diseases like Alzheimer's or frontotemporal dementia. Thus
enabling dr. Stephen hawking to continue to work in the field of physics.
• Autonomic functions are regulated by a different set of neurons, and
disruptions in these functions are not a characteristic feature of ALS.
• Medical interventions, healthcare, variability in disease progression and
technology like his iconic speech-generating device, enabled Hawking to
continue his work and maintain a high level of intellectual engagement despite
his physical limitations. But it is important to remember that everybody’s
experience with ALS is unique and can vary for everyone widely.

15. Currently, there is no cure for
Amyotrophic Lateral Sclerosis (ALS).
Treatment aims to manage symptoms
and enhance quality of life. Therapies
like physical and occupational therapy,
medications to alleviate symptoms, and
assistive devices are utilized.
Amyotrophic lateral sclerosis (ALS)
carries profound emotional implications,
as individuals facing this disease endure
the loss of motor functions. The
emotional toll is heightened by the
gradual decline in independence,
communication difficulties, and the
impact on relationships. Coping with ALS
involves navigating complex emotions
such as grief, frustration, and resilience.

16. Thank you!
Studying neurobiology has provided me with a deeper
understanding of intricate workings of our nervous system. This
knowledge has allowed me to look at my surroundings with a
different perspective. As I am a psychology student, it has further
enhanced my overall comprehension of human behaviour and I
look forward to integrate this knowledge with my curriculum. I
have gotten some insights which are really useful for me in my field
of study. I am now able to understand a lot of concepts and can
dive more deep into articles and research papers. This course has
also given me an important lesson that your diagnosis does not
defines your whole life. This course has further strengthen my
curiosity about neurobiology and I look forward to learn more!

17. Resources
neurobiology of brain and behaviour (coursera)- week 1, week 2, week 7 and week 10
https://www.hopkinsmedicine.org/health/conditions-and diseases/amyotrophic-lateral-sclerosis-
als#:~:text=ALS%20is%20a%20fatal%20motor,no%20known%20cure%20for%20ALS.
https://www.mayoclinic.org/diseases-conditions/amyotrophic-lateral-sclerosis/symptoms-causes/syc-20354022
https://www.ninds.nih.gov/health-information/disorders/amyotrophic-lateral-sclerosis-als
Blokhuis, A.M., Groen, E.J.N., Koppers, M. et al. Protein aggregation in amyotrophic lateral sclerosis. Acta
Neuropathol 125, 777–794 (2013). https://doi.org/10.1007/s00401-013-1125-6
T. Philips, J.D. Rothstein, Glial cells in amyotrophic lateral sclerosis, Experimental Neurology, Volume 262, Part B,
2014, Pages 111-120
https://youtu.be/T7pdPgf0rWA?si=NwzsVEgr5PfOf3OW