BILD 2: Multicellular Life - Cancer and the Human Nervous System

Agenda and Class Information

  • Course: BILD 2: Multicellular Life
  • Class Session: Class #8
  • Date: Wednesday, Apr. 15, 2026
  • Primary Question: How do the cells of multicellular organisms communicate through neurons?
  • Agenda Highlights:
        - Welcome and introduction to the agenda.
        - Introduction to the human nervous system.
        - Ions in the nervous system.
        - Homework and Reflection.

Cancer Learning Objectives

  • Be able to explain the basic commonalities and differences between all forms of cancer.
  • Explain the reasoning behind why many cancers share similar characteristics with embryonic development.
  • Predict whether mutations or experimental manipulations affecting the following will promote cancer:
        - Proto-oncogenes.
        - Tumor suppressors.
        - DNA repair genes.
        - Angiogenesis.
        - Differentiation.
  • Explain the basic rationales underlying the three major forms of cancer treatment currently utilized.

The Connection Between Cancer and Development

  • Cancer and embryonic development share several key characteristics:
        - There are many rapidly dividing cells.
        - Many cells exhibit migration and movement throughout the body.
        - Cells in both states are generally not differentiated and are not performing their mature, adult functions.
  • Gene Expression: Many cancers re-activate gene expression patterns that are typically seen only during developmental stages.
  • Cellular Differentiation Status:
        - Generally, fully differentiated cells do not divide.
        - For a differentiated cell to become cancerous, it must lose aspects of its adult function.
        - Cancerous cells look and behave like immature, less fully differentiated cells.
  • Functional Implications (Example: Lymphoma):
        - Lymphoma is a cancer where immune cells called lymphocytes proliferate.
        - Normally, lymphocytes function to fight infections.
        - Patients with lymphoma have a worse ability to fight infections because the rapidly dividing cells are undifferentiated and not performing their mature functions.

Genetic Classifications in Cancer Growth

  • Tumor Suppressors: These genes normally repress growth. When they are inactivated (via mutation), it promotes cancer.
  • Proto-oncogenes: These genes normally encourage growth. When they are over-activated or inappropriately activated, they become oncogenes that promote cancer.
  • Genes that Promote Differentiation: These are normally turned on to promote differentiation and turn off growth. When inactivated, they promote the growth and spread of cancer.
  • DNA Repair Genes: These normally fix errors in DNA. When inactivated, mutations accumulate more rapidly, promoting cancer.
  • Genes that Promote Angiogenesis: These genes normally promote the growth of blood vessels. When over-activated or inappropriately activated, they promote tumor growth and the spread of cancer (metastasis).

Distinctive Features Between Cancers

  • While cancers share commonalities, they differ in several ways:
        - Location: Where the cancer originates in the body (e.g., glioblastoma multiforme in the brain vs. breast cancer).
        - Mutation Profile:
            - Which specific genes are mutated.
            - The underlying causes of those mutations.
        - Treatment Protocols: How the specific cancer is treated.

Cancer Treatment Rationales

  • Current treatments generally involve a combination of the following approach:
        - Radiation and Chemotherapy: The primary rationale is to kill rapidly dividing cells.
        - Surgery: The rationale is to physically cut the tumor out of the body.
            - Note: This would not be effective for leukemia (cancer of the white blood cells) because the cancer is not localized in a removable solid mass.
        - Immunotherapy: This enhances the body's own immune system to identify and kill cancerous cells.

Introduction to the Nervous System: Learning Goals

  • Compare and contrast long-distance communication in the endocrine system versus the neural system within the mammalian body.
  • Identify and state the roles of neurons and various glia (astrocytes, oligodendrocytes, Schwann cells, microglia).
  • Contrast the Central Nervous System (CNS) and Peripheral Nervous System (PNS) regarding location and cell types.
  • Draw and label neuron anatomy: soma, axon, axon terminals, dendrite, and nucleus; indicate the direction of information flow.
  • Predict changes in voltage-vs-time graphs of action potentials when perturbing membrane potential, Na+Na^+ channels, K+K^+ channels, or the Na+/K+Na^+/K^+ pump.
  • Predict how myelination or changes in ion channel properties affect action potential propagation.
  • Predict signaling changes between neurons and targets if neurotransmitter release, receptors, or synaptic clearance are perturbed.

Long-Distance Communication: Endocrine vs. Nervous System

  • Endocrine System:
        - Uses hormones as signaling molecules.
        - Endocrine glands secrete hormones into the surrounding fluid.
        - Signal Transport: Transported through the blood.
        - Targets: Reaches cells throughout the entire body.
        - Speed: Reaches target cells more slowly.
        - Duration: Effects tend to last for a longer amount of time.
  • Nervous System:
        - Uses signaling by nerve cells (neurons).
        - Signal Transport: Signals are electrical or chemicals carried through extracellular fluid.
        - Targets: Only targets neurons, muscles, and some glands.
        - Speed: Reaches target cells more quickly.
        - Duration: Effects tend to last for a shorter amount of time.

Defining Hormones

  • A hormone is a signaling molecule that meets four criteria:
        1. Produced in low concentrations by one part of an organism's body.
        2. Transported to other parts of the body.
        3. Binds to a specific receptor.
        4. Triggers responses in target cells and tissues.

Nervous System Organization and Information Flow

  • Central Nervous System (CNS): Consists of the brain and spinal cord; it is the primary site of information integration.
  • Peripheral Nervous System (PNS): Includes everything outside the brain and spinal cord.
  • Flow of Information:
        - Sensor: Detects stimulus.
        - Sensory Neuron: Transmits signal to the CNS.
        - CNS (Brain & Spinal Cord): Integrates the information.
        - Motor Neuron: Receives integrated signal and stimulates effector targets (muscles or glands).
  • Epilepsy: Defined as many episodes of seizures; seizures are characterized by uncontrolled electrical activity in the brain.

Types and Functions of Glia

  • Central Nervous System (CNS) Glia:
        - Oligodendrocytes: Function to insulate neurons with myelin. A single oligodendrocyte can myelinate multiple neurons simultaneously.
        - Astrocytes: The main support cells for the brain. They transport nutrients from the blood to neurons, balance the ionic and chemical environment, and are involved in care, maintenance, and healing of brain tissue.
        - Microglia: Function as the "white blood cells" of the brain; they fight microorganisms and scavenge or clean up debris.
  • Peripheral Nervous System (PNS) Glia:
        - Schwann Cells: Function to insulate cells of the PNS with myelin. Unlike oligodendrocytes, one Schwann cell myelinates only one axon.
        - Clinical Note: Schwann cell degeneration would lead to symptoms such as difficulty walking, muscle weakness, and loss of the knee reflex, but would not typically be expected to cause problems with reading (a CNS task).

Neuron Anatomy and Communication

  • Diversity: Neurons exhibit high morphological diversity depending on their specific role.
  • Structural Components:
        - Dendrites: Receive incoming signals from other neurons.
        - Cell Body / Soma: Contains the nucleus, which triggers gene expression.
        - Axon: The structure through which the signal travels to other cells.
        - Axon Terminals: Send output signals to target cells.
  • Information Flow Direction: Dendrites (Input) $\rightarrow$ Cell Body $\rightarrow$ Axon $\rightarrow$ Axon Terminals (Output to Target).
  • Synapse: The chemical junction where neurons send signals to each other. This triggers electrical signals within the neuron that travel down its length.

The Action Potential (AP)

  • Also referred to as "spikes" or "firing."
  • Definition: An electrical signal that travels down the axon to allow cells to communicate over long distances quickly and consistently.
  • Path: Starts at the beginning of the axon (the axon hillock) as a result of input and ends at the axon terminals, where it initiates signaling to the next neuron.
  • Electrical States:
        - Membrane Potential: The voltage measured inside a cell.
        - Resting Membrane Potential: The voltage of a cell when it is at rest.
        - Action Potential: A specific pattern of electrical response triggered when a cell receives stimulation.

Causal Mechanistic Reasoning in Biology

  • Mechanism: Complicated biological processes are composed of smaller, relatively simple components.
  • Causality: For each piece of a mechanism, specific inputs cause specific effects. Understanding biology requires identifying what inputs cause each piece to act.

Molecular Players in the Action Potential

  • Na+/K+Na^+/K^+ Pump:
        - Trigger: Works continuously and slowly.
        - Effect: Transports Na+Na^+ to the outside of the cell and K+K^+ to the inside.
  • Voltage-gated Na+Na^+ Channel:
        - Trigger: High voltage (above a specific threshold).
        - Effects:
            1. Opens immediately.
            2. Allows fast inward flow of Na+Na^+ ions.
            3. Inactivates (shuts off) shortly after opening.
  • Voltage-gated K+K^+ Channel:
        - Trigger: High voltage (above threshold).
        - Effects:
            1. Opens after a short delay.
            2. Allows fast outward flow of K+K^+ ions.

Ion Transport Mechanisms: Pumps vs. Channels

  • Ion Pumps:
        - Moves substances through the membrane.
        - Highly selective for certain ions.
        - Uses Active Transport (requires ATP).
        - Operating speed is slow.
        - Primary function is to create concentration gradients by transporting molecules against their gradients.
  • Ion Channels:
        - Moves substances through the membrane.
        - Highly selective for certain ions.
        - Uses Passive Transport (does not use ATP).
        - Operating speed is fast.
        - Primary function is to allow ions to diffuse down their concentration gradients.

Diffusion Scenario

  • Consider a hypothetical cell with:
        - 50 mM Na+50\,mM\,Na^+ outside.
        - 50 mM K+50\,mM\,K^+ inside.
        - Membrane is only permeable to Na+Na^+.
  • Result: Na+Na^+ will enter the cell via diffusion, while K+K^+ will stay put because the membrane is not permeable to it.