Lecture 1 (chapter 2) Flashcards

Cellular Components and Functioning

1
Q

Intracellular Components and Functions

A

• Cell membrane
• Nucleus: Contains chromosomes and nucleolus (where DNA is stored)
• Ribosomes (packages things)
• Smooth and rough endoplasmic reticulum:
o Rough: Contains ribosomes that produce proteins to be transported within and out of the cell
o Smooth: production of lipids and transports proteins
• Mitochondria: Produces adenosine triphosphate (ATP), which the cell uses as an energy source
• Golgi complex: Assembles and package proteins to be sent to other destinations
• Cytoskeleton: Strands of proteins maintain the internal structure of a cell
• Synaptic vesicles
• Dendrites: branches coming out of cell body with one long one called the axon which connects cells and allows for neurotransmission.
• Axon Damage: if It severed it can stop communication between cells; characteristic of Alzheimer’s disease – the main reason people get Alzheimer’s is that their axons start breaking apart.
• Axons connect to another cells dendrites where molecules are released and information is transmitted to the other cell.

*How many connections are in the brain 100 trillion connections. This makes it so much
harder to identify what is going on in the brain, identify, explain, and treat problems.

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2
Q

cell structure

A

• Strands of proteins maintain the internal structure of a cell (cable) by forming the cytoskeleton
• Large strands are known as microtubules, and they extend from the cell body through the axon to the terminal bouton
o Anterograde transport
o Retrograde transport

*When the microtubules are dysfunctional the connections between cells are reduced

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3
Q

Terminal boutons

A
  • Contain vesicles filled with substances that are released nearby other cells
  • Dendrites are treelike structures that emerge from the cell body of the neuron and receive messages from other neurons
  • Located on the dendritic branches are protrusions known as dendritic spines
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4
Q

Dendrites and synapses

A

• Each dendrite receives thousands of inputs from other neurons via synapses
• Synapse: Site at which axons make functional contact with their target cells
o Space between the terminal bouton of a neuron sending a message and the area of a neuron that is receiving the message (molecules transmitted across the cell; treatment reduces or increases neurotransmitters binding to the synaptic cleft and releasing; dopamine, serotonin, acetylcholine etc.)

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5
Q

Types of synapses

Axons which connect to…

A
  • Axosecretory
  • axon terminal secretes into BLOOD
    VESSEL
  • Axoaxonic
  • axon terminal secretes into ANOTHER
    AXON
  • Axodendritic
  • axon terminal connects to DENDRITE
    SPINE
  • Axoextracelluar
  • axon terminal secretes into
    EXTRACELLULAR FLUID
  • Axosomatic
  • axon terminal secretes on SOMA
  • Axosynaptic
  • axon terminal secretes on another
    AXON TERMINAL

*Point is that cables carry information to different areas of the cell body and these complex connections create the neural circuit.

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6
Q

Synapse

A
  • Terminal bouton of the neuron: Presynaptic
  • Space between presynaptic and postsynaptic neurons: Synaptic cleft
  • Neuron that receives the message: Postsynaptic

*Releases neurotransmitters from terminal button into presynaptic cell
into synaptic cleft. Will bind to the postsynaptic cell and if reaches
excitatory threshold will cause the neuron to fire (change from
receptor to transmitting neuron) all occurs at the molecular level.

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7
Q

Action potential

A

Action potential
• Negative and positive particles called ions are unevenly distributed in the intracellular and extracellular fluid
• The intracellular fluid contains more potassium ions (K+) than the extracellular fluid and smaller amounts of chloride (Cl−) and sodium (Na+) ions
o Positive ions outside the cell (Na+ and K+) are attracted to the intracellular fluid however the negative ions such as Cl− are repelled by the negative charge of the intracellular fluid
o This attraction between positive and negative ions and the repulsion between like-charged ions produce energy in the form of electrostatic pressure (energy source to allow diffusion when channels open)
• An action potential lasts less than 1 millisecond until neurons are quickly restored to the resting potential

What we need to know:
• Neurons are a unit of information which primary function is to pass it to another cell. It is passed by molecules (i.e., neurotransmitters) released from presynaptic terminal button into synaptic cleft, they bind to receptor site in the postsynaptic neuron (site varies), if the excitatory threshold is met an action potential occurs and channels in the cell membranes open and allows (diffusion and __ energy) +/- to enter and exit the cell. Refractory period where more than -70 charge in cell where no communication can occur. K+ ions coming into cell and –ions leaving the cell depolarizes the cell (reduce – charge to 70) at its resting cell potential.
• Action potential = receptor channels open, ions are passed, that excitatory threshold is met and action potential to occur.
• Opposite charges attract, + in extra attracted to – charge of intra; this changes the charge.

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8
Q

Neurotransmitters

Chemicals found in the brain are considered to be a neurotransmitter if:

A
  • Are synthesized in neurons
  • Are released, occupy a receptor, and result in an effect in another cell
  • Are cleared from the synaptic cleft following release
  • Effects can be replicated by an experimental substance
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9
Q

Neurotransmitter classes

A
  • Transmitter gases
  • Large molecule transmitters: Molecular weights from 200 to 5,000
  • Small molecule transmitters: Molecular weights less than 200
  • Transmitter substances are unequally distributed throughout the brain
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10
Q

Glutamate

A

Glutamate
• Principal excitatory neurotransmitter
• Glutamatergic neurons are widely distributed
• Glutamate receptors are usually located on parts of the dendrite
• Glutamate is cleared from the cleft primarily by glia cells
• Glutamate is also reclaimed from the synaptic cleft by transporter proteins located on the presynaptic neuron
Glutamate imbalance linked to:
o Learning and memory
o Bipolar disorder and mania
o Schizophrenia
o Depression

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11
Q

Gamma-Amino Butyric Acid (GABA)

A
Gamma-Amino Butyric Acid (GABA)
•	Principal inhibitory neurotransmitter in the brain
•	Widely distributed throughout the brain
     Implicated in:
o	Epilepsy
o	Tourette’s disorder
o	Anxiety disorders
o	Neurodegenerative disease
o	Post-traumatic stress disorder (PTSD)
o	Alzheimer’s disease
o	insomnia
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12
Q

Monoamine neurotransmitters

A

Monoamine neurotransmitters
• Catecholamines
• Dopamine (DA)
• Epinephrine (EP)
• Norepinephrine (NE)
• Indolamines
• Serotonin
• Melatonin
*Conditions are treated with medication to make molecular changes that target the release of
neurotransmitters. It is common for people to treat disorders with medication without
understanding what effects it is having on the persons brain chemistry and subsequently the
person themselves. We treat people without understanding what it does.

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13
Q

Transmitter gases

A

• Easily cross the cell’s membrane, diffuse across the cleft, and enter other cell membranes
• Short-lived
• Examples:
o Hydrogen sulfide (H2S): Role in the release of hormones from the hypothalamus
o Carbon monoxide (CO): Regulates olfactory and hypothalamus neurons
o Nitric oxide (NO): Learning and memory

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14
Q

Large molecule neurotransmitters

A

• Peptides that consist of two or more amino acids connected by peptide bonds
• Examples:
o Angiotensin
o Cholecystokinin
o Somastostatin
o Oxytocin: Modulatory effect on pain perception

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15
Q

Small molecule neurotransmitters

A
  1. Amino acids: Aspartic acid, gamma-aminobutyric acid (GABA), glutamate, and glycine – Major transmitters in the brain
  2. Monoamines:
    o Catecholamines: i.e. Dopamine, epinephrine, noreepinephrine
    o Indolamines: i.e. serotonin
  3. Acetylcholine
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16
Q

Aspartate

G…..

A

• Abundant in the brain
• Excitatory effect
• Aspartate and glutamate are synthesized in the terminal bouton
• Receptor dysfunction for both amino acids has been implicated in schizophrenia
o Ketamine, a drug that blocks glutamate receptors, produces schizophrenia-like symptoms in healthy adults

17
Q

Dopamine

High levels in…
What effect can it have?
What breaks it down?

A

Dopamine
• Concentrated in the basal ganglia, substantia nigra, and tegmentum and have widespread projections to the frontal regions of the brain (produced in subcortical structures; cell death in the substantia nigra then we can find localized brain regions implicated in disorders like Parkinson’s disease; understanding this lets us know how to treat people with molecule and brain region to target)
• Involved in movement, attention, motivation, and learning
• Implicated in schizophrenia, obsessive compulsive disorders, Tourette’s disorder, Parkinson’s disease, and addiction Dopamine
• Depending on the receptor, dopamine can have an excitatory, inhibitory, or modulating effect on the cell. This variance in distribution of receptors is consistent with the large number of brain functions in which dopamine appears to be involved
• Dopamine is broken down by monoamine oxidase (MAO) and catechol-o-methyl transferase

18
Q

Norepinephrine and Epinephrine (Adrenaline System)

A

Norepinephrine and Epinephrine (Adrenaline System)
• Contained in the brain stem
• Project to the hypothalamus, thalamus, and the cortex.
• Implicated in anxiety, mood disorders, ADHD, panic disorder, major depressive disorders

*We can’t regenerate dead neurons; we can manipulate
molecular chemical release in the brain. Manipulate
dosage till it has the desired effect on removing the
undesirable behaviour.

19
Q

Serotonin

A

Serotonin
• Concentrated in the brain stem and midbrain
• Projection system is widespread
• Implicated in arousal, wakefulness, sleep, appetite and eating behavior, stress response, mood, and motor behavior
• Serotonin synthesis is substantially higher in children than adults
• Implicated in anxiety or depression

20
Q

Acetylcholine

A

Acetylcholine
• Acetylcholine is widespread throughout the central and peripheral nervous system
• Implicated in attention, memory, learning, various psychiatric disorders, and dementias

21
Q

Psychopharmacology

A
  • Drugs prescribed to treat cognitive and behavioral symptoms of psychological/psychiatric disorders are known as psychotropic medications
  • Psychotropic medications can improve cognitive and behavioral symptoms in many individuals, but they do not cure the underlying cause of psychological disorders

*They do not cure you. The reduce symptoms but cannot regenerate the dead cell/damage
already sustained. It’s the same chemistry as giving children illegal drugs.

22
Q

psychotropic medication stats

A

o Most common medications were antidepressants and antianxiety medications
o 8 out 10 reported using the medications long term
o 20.8% of white adults reporting use of psychotropic medications versus 8.7% of Hispanic adults
o Women were more likely than men to report taking psychotropic medications
o Use increased with age (25.1% of adults aged 60–85 years versus 9.0% of those aged 18–39 years)

*Very high number of people on medication. Imbalances influenced by genetics, age, gender,
ethnicity (access to health care or genetics).

• Psychotropic medication has increased among children of all ages

23
Q

Caveat to drug prescriptions!

A
  • Despite the widespread use of psychotropic medications among children, adolescents, and adults, the precise mode action of most drugs used to treat psychiatric disorders is unknown!
  • “At the molecular level an explanation of the action of a drug is often possible; at the cellular level, an explanation is sometimes possible; but at the behavioral level, our ignorance is abysmal (i.e., we know which neurotransmitter is increased or decreased but that it all. We do not know how explain how this effects their cellular functioning and behaviour; when people stop taking medication their behaviour will change because their molecular level changes have occurred by the drug)
24
Q

Pharmacokinetics

A

• The process of drugs being absorbed, distributed, metabolized, and excreted by the body is known as pharmacokinetics

25
Q

Medication effects

A

Medication effects
• The amount of psychotropic drug needed to attain a therapeutic effect can vary widely among individuals, as can the undesirable side effects of psychotropic drugs
o Emotional blunting occurs in 50% of patients taking antidepressant medications

26
Q

Agonist and antagonist (all medications fall into one of these categories)

A
  • Agonist: facilitate or enhance the effects of neurotransmitters (serotonin-reuptake-inhibiters – inhibits the removal of serotonin from synaptic cleft)
  • Antagonist: Interfere with or reduce the effects of neurotransmitters (blocks receptors to stop binding)
  • Neurotoxins can produce either antagonistic or agonistic effects
  • Curare occupies acetylcholine receptors and blocks acetylcholine from attaching to the receptor Curare is therefore an acetylcholine antagonist
  • Black widow spider venom increases the amount of acetylcholine released by the terminal bouton and is therefore an acetylcholine agonist.
  • Antipsychotic medications often target and block dopamine receptors, and hence are considered dopamine antagonists
27
Q

Types of psychotropic drugs

A
Types of psychotropic drugs
•	Antianxiety
•	Antidepressants
•	Antipsychotic
•	Mood stabilizers
•	Stimulants
28
Q

Anxiety disorders are the most …..

A

• Anxiety disorders are the most prevalent psychiatric disorder worldwide, occur more commonly in women, and tend to decrease in prevalence later in life

29
Q

Antianxiety medication, Benzodiazepines, Alcohol

A
Antianxiety medication
•	Heterogeneous group of conditions that share features of excessive fear, anxiety, and related behavioral disturbances
o	Generalized anxiety disorder (GAD)
o	Separation anxiety disorder
o	Specific phobia
o	Social anxiety
o	Panic disorder
•	Anxiety disorders are the most prevalent psychiatric disorder worldwide, occur more commonly in women, and tend to decrease in prevalence later in life

Benzodiazepines (Ativan, Xanax, Valium, Klonipin)
• Insomnia
• Muscle relaxation
• Seizure disorders
• Anxiety
*Benzodiazepines are GABA agonists, and modulate neurotransmission by attaching to part
of the GABAa receptor

Alcohol
• Sleeping aids, barbituates, and alcohol attach to a different part of the GABA receptor and mimic the effects of GABA
• The end result of these drugs is similar to benzodiazepines in that neural inhibition is increased throughout the brain

Mixture of alcohol and benzodiazepines can have additive negative effects

30
Q

Antidepressant medications

categories

A

Antidepressant medications
• Anxiety disorders
• Chronic pain
• Migraines
• ADHD
• OCD
• Most often used to treat depressive disorders
• 80% of individuals with a mood disorder respond to treatment that typically involves antidepressants and some form of psychotherapy
• On average suicide risk of 4% compared to 2% for placebo in children

Categories of antidepressants
• Monoamine oxidase inhibitors
• Tricyclic antidepressants
• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin and norepinephrine reuptake inhibitors (SNRIs)
• Atypical antidepressants

Monoamine Oxidase Inhibitors (MAOIs)
• Monoamine oxidases are enzymes (MAO-A and MAO-B) that metabolize serotonin, dopamine, and norepinephrine
• The end result of these inhibitors is that more neurotransmitter is available for release and for activating postsynaptic receptors

Tricyclic Antidepressants
• Tricyclic antidepressants block the reuptake of norepinephrine and serotonin by binding to the presynaptic transporter proteins
• Tricyclic antidepressants also attach to acetylcholine and histamine receptors
• Tricyclic antidepressants can produce sudden-onset headaches, seizures, and stroke

31
Q

Antipsychotic medications

A
Antipsychotic medications
•	Psychotic disorders
•	Tourette’s disorder
•	Borderline personality disorder
•	ASDs
•	Anxiety
•	Bipolar disorder
•	20% to 40% of patients will develop tardive dyskinesia, characterized by involuntary muscle movements, primarily in the facial region
  • Primarily block the dopamine (D2) receptors
  • Reduce the level of dopamine that is synthesized by neurons
  • Antipsychotics often result in immediate improvement of symptoms
  • Greatest symptom relief often occurs within the first two weeks of treatment
32
Q

Mood stabilizers

A
Mood stabilizers
•	Primarily for bipolar disorder
o	Lithium 
o	Anticonvulsants 
•	The precise mode of action of lithium is poorly understood

Anticonvulsant gaba and norepinephrine agonist

33
Q

Psychostimulants

A

Psychostimulants
• ADHD
o Methylphenidate
o Amphetamine derivatives
o ADHD is estimated to affect 3% to 7% of the school-age population and 4% of adults worldwide
• Blocks the transporter protein for dopamine (DAT) resulting in more dopamine available in the synaptic cleft