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Understanding the Brain through
Disease
Tammy Due
Masconomet Regional High School
Lecture Outline
Brain Overview
Neural Anatomy
Neurological Diseases/Current Research
 Parietal Lobe
Frontal Lobe

Occipital
Lobe

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Temporal Lobe
Cerebellum
Brain Overview
www.cs.princeton.edu/.../ sugcon/models/brain.png
Pons
Neuroanatomical
 Anatomy of the Brain
Cerebrum
Corpus Callosum

Ventricles

Thalamus
Hypothalamus
Midbrain
Pituitary Gland
Cerebellum
Pons
Medulla Brain Stem

http://www.ama-assn.org/ama1/pub/upload/images/446/brainside.gif
 Cerebrum
Makes up the left and right hemispheres of
a vertebrate forebrain.
Responsible for integrating memory,
learning, emotions and other complex
functions of the brain.
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Brain slide
 Hypothalamus
Part of the forebrain involved with
maintaining homeostasis.
The hypothalamus is especially important in
coordinating the endocrine and nervous
systems.
Secretes hormones of posterior pituitary
which regulate the anterior pituitary.
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Brain slide
 Pituitary Gland
Used to be called the master gland because so many of
its hormones regulate other endocrine functions.
Anterior pituitary: secretes hormones directly into the
blood stream. The hypothalamus release inhibitory
hormones.
Anterior pituitary hormones: growth hormone (GH),
insulin growth factors, prolactin (PRL), Follicle
stimulating hormone (FSH), leutinizing hormone (LH),
thyroid stimulating hormone (TSH), adrenocorticotropic
hormone (ACTH), melanocyte-stimulating hormone
(MSH), and endorphins
Posterior pituitary: the two hormones released by the
posterior pituitary are produced by the hypothalamus.
Oxytocin and Antidiuretic hormone (ADH)
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Brain slide
 Brainstem
Medulla or medulla oblongata: contains
centers that control breathing, heart & blood
vessel activity, swallowing, vomiting &
digestion.
Pons: have nuclei that regulate the breathing
centers in the medulla.
Brainstem is responsible for movement.
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Brain slide
 Cerebellum
Part of the hindbrain
Functions in unconscious coordination of
movement and balance.
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Brain slide
 Midbrain
Develops into sensory integrating and relay
centers that sends sensory information to
the cerebrum.
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 Thalamus
One of the integrating centers in the
vertebrate forebrain.
Neurons in the thalamus relay neural input
to specific areas of the cerebral cortex and
regulates what information goes to the
cerebral cortex.
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Return to
Brain slide
 Ventricles
Four spaces in the vertebrate brain that are
filled with cerebrospinal fluid.
Cerebrospinal fluid conveys nutrients,
hormones, & white blood cells across the
BBB to different parts of the brain.
Fluid also is important in cushioning the
brain.
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 Corpus Callosum
Thick band of nerve fibers that connects the
right & left hemispheres in placental
mammals. This connection allows for the
hemispheres to process information
together.
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Lecture Outline
Brain Overview
Neural Anatomy
Neurological Diseases/Current Research
These cells control brain function
on a cellular level. What are they
called?

Image courtesy of Dr. Joshua Sanes, Harvard University, 2005

 The Neuron comes in many
shapes and sizes

http://www.mind.ilstu.edu/images/neuron_types.gif
 Typical Neuron

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Soma (nucleus)

Myelin Sheath

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 Osm-10

Image by T. Due, Harvard University, 7/15/05

Osm-10 is a chemoreceptor found in C. elegans. This worm contains
a transgene encoding the osm-10 promoter fused to GFP (Harvard Medical School).
 Action Potential I
1. Resting state: -70mV
2. Neuron receives
stimulus, gated ion
channels open and
sodium(Na+) moves into
the cell, this is
2 3
depolarization. The
stronger the signal the
more channels that open.
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When the threshhold
potential is reached (+55
to +50mV) an action
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impulse is triggered.
This is an all or none
event.
 Action Potential II
3. During repolarization the sodium channels
close and potassium channels open. K+
moves out of the cell making the cell more
negative than its environment.
4. The K+ gates are slow to close which may
result in undershooting. This means that the
negative voltage inside the cell goes lower
than the resting state.

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Action
Previous Potential
Slide Video
 Typical Neuron

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Soma (nucleus)

Myelin Sheath Node of Ranvier

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 The Synapse
Mitochondria

Synaptic Microtubule
Vesicle
Synaptic vesicle
being transferred

Cisternae
Terminal end

Synaptic Cleft

Vesicle at synaptic
cleft Presynaptic
Membrane Postsynaptic
Membrane

http://www.staff.city.ac.uk/c.r.legg/index.2.jpg
 Real Synapses

From Dr.Venkatesh N. Murthys, Harvard Photo by T. Due, Harvard University, 7/2005

University, 7/2005 These C. elegan worms contain a transgene encoding unc-49 gene
(GABA receptor) fused to its own promoter and GFP
(Harvard Medical School)
Lecture Outline
Brain Overview
Neural Anatomy
Neurological Diseases/Current Research
 ADHD
Symptoms:
Inattention, impulsivity, hyperactivity

Causes:
1. Environmental Agents: cigarettes, smoking, lead
May affect neuronal connections being formed in developing
brain.
2. Brain Injury
Evidence has shown that few with ADHD are the result of
brain injury.
3. Food Additives & Sugar
We once thought that refined sugar and food additives caused
ADHD but in studies that restrict a patients diet there was
little effect on behavior and learning.
 Causes of ADHD continued
4. Genetics:
25% of close relatives of someone w/ ADHD also
have ADHD. This rate is only 5% in the general
public.
Twin studies show a strong genetic influence.
 Brain Study Results
Technology used: fMRIs, PET scans, single
photon emission computed tomography (SPECT)
ADHD children showed 3-4% smaller brain
volume in all regions--frontal lobes, temporal gray
matter, caudate nucleus and cerebellum.
ADHD patients on medication showed no
difference from controls in amount of white matter
(connections).
fMRIs show that there is less glucose used in the
frontal lobes of patients with ADHD
 Brain Images: ADHD

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Brain scan images produced by fMRI show In men who had ADHD, PET (positron
differences between an adult with Attention emission tomography) scans showed that
deficit Hyperactivity Disorder (right) and they processed a memory task in visual
an adult free of the disease (left). areas in the occipital lobe of the brain, as
Zametkin, et. al., 1990 indicated by the yellow spots in the left
image. Non-ADHD men used the temporal
and frontal lobes, shown at right
(ABCNEWS.com)
 Treatments
Medication: shows positive results when appropriate
medication and dosage is given
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Ritalin, Adderall, Concerta: focus has been creating long lasting
drugs with fewer side effects. All are stimulants and work in a
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similar manner to cocaine.

Strattera: a non-stimulant medication for ADHD
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Some side effects of medication: upset stomach, headaches,
dizziness, decreased appetite, sleep issues
Behavioral Therapy (not best when used alone)
Behavioral therapy, Psychotherapy
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Combination Therapy: medication and behavioral

 Huntingtons Disease (HD)
Frequency: 1/30,000 Americans

Symptoms of HD
Uncontrolled movements
Loss of intellectual faculties
Emotional disturbances
Mood swings
Irritability
Depression
Difficulty driving
Concentration on intellectual tasks decreases with age.
 Biological Basis
Autosomal dominant disorder
Gene located on chromosome 4
Within the gene CAG repeats occur 11-30X in a
normal person.
A person with 36-125 CAG repeats will tend to
develop HD between 30-40 years of age.
If someone has >60 repeats they tend to develop
HD much earlier, in their 20s.
 The result of CAG repeats
The gene that is affected produces the
Huntingtin protein in normal cells
The protein that is created is a more polar
molecule which tends to interact with other
brain proteins differently. Ex. HAP 1
 Molecular Basis of Huntingtons
Disease

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 What areas of the brain are
affected by changes in Huntingtin
protein?
Neurons are damaged in the basal ganglia,
especially the caudate nucleus and globus
pallidus.

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 Treatment
Medications are prescribed to decrease the
symptoms of HD.
Some medications treat fatigue,
hyperexcitability, and restlessness.
Other medications treat the control
emotional and movement problems.
 Current Research on HD
Silencing of mutant gene, decreases protein
production which results in decrease of HD
symptoms. Gene was silenced using RNAis.
Using rodent and primate models, scientists have
transplanted fetal brain tissue into brains damaged
by HD. The transplanted cells survived.