L2 (cont.): Comprehensive Study Notes on Neuronal Structure, Myelination, and CNS/PNS Pathology

Structural and Functional Regions of Neurons

• Neurons are divided into three main functional regions responsible for receiving, transmitting, and passing along electrical and chemical signals:

  • Receptive Region:

  • Function: Receives chemical or electrical signals from other neurons or environmental stimuli.

  • Signal Types: Chemical signals occurring at chemical synapses or electrical signals occurring at electrical synapses.

  • Endings & Terminology:

    • In the Central Nervous System (CNS) and multipolar neurons, inputs are received by branching processes called dendrites.

    • In the Peripheral Nervous System (PNS) sensory afferent division, specialized endings called sensory receptors sense environmental conditions such as temperature and pressure, sending that information toward the CNS.

  • Conducting Region:

  • Structure: Composed of the axon.

  • Function: Conveys electrical impulses away from the neuron cell body along the axon.

  • Myelination Impact: Axons can be myelinated or unmyelinated. Myelinated axons conduct signals at significantly higher conduction speeds than unmyelinated axons.

  • Secretory Region:

  • Structure: Formed by the terminal branching end of the axon, known interchangeably as axon terminals, telodendria, or synaptic knobs (the enlarged, knob-like tips at the extremities of the terminal branches).

  • Function: Secretes neurotransmitters across the synaptic gap to communicate with effector cells or adjacent neurons.

• Neurons are categorized into three main structural types:

  • Multipolar Neurons:

  • Structure: Possess multiple dendrites extending from the cell body and a single axon.

  • Examples: Spinal motor neurons, pyramidal cells, and Purkinje cells.

  • Distribution: Located in both the CNS and the PNS. In the PNS, lower motor neurons are multipolar cells that belong to the efferent (motor) division and synapse directly onto skeletal muscle tissue.

  • Bipolar Neurons:

  • Structure: Possess two distinct processes extending from the cell body (one axon and one dendrite).

  • Function & Distribution: Form part of the sensory afferent system dedicated to special senses (e.g., vision, olfaction).

  • Pseudo-unipolar Neurons:

  • Structure: Possess a single short process extending from the cell body that bifurcates into a peripheral process and a central process.

  • Function & Distribution: Form part of the sensory afferent system for general senses (e.g., pain, touch, pressure, temperature), utilizing sensory receptors at their peripheral endings.

Nervous System Terminology and Tissue Classification

• Precise anatomical terminology distinguishes neuronal structures based on whether they reside in the Central Nervous System or the Peripheral Nervous System:

  • Bundles of Axons:

  • CNS: Termed tracts.

  • PNS: Termed nerves.

  • Clusters of Neuron Cell Bodies:

  • CNS: Termed nuclei (singular: nucleus). The word derives from the classical definition of a "nucleus" as the central focal point of a structure.

  • PNS: Termed ganglia (singular: ganglion).

  • Functional Role of Cell Bodies: The neuron cell body acts as the primary metabolic center and functions as part of the receptive region of the neuron.

• Macroscopic Organization of Nervous Tissue:

  • White Matter:

  • Composition: Composed predominantly of myelinated axons.

  • Function: Facilitates rapid communication and high-speed signal conduction across different regions of the nervous system.

  • Appearance: The characteristic white color stems from the dense lipid content of the plasma membranes provided by myelinating glial cells.

  • Gray Matter:

  • Composition: Composed of unmyelinated axons, neuron cell bodies (nuclei in the CNS), dendrites, and neuroglia.

  • Function: Serves as the primary site of signal processing, integration, and synaptic transmission.

  • Evolutionary Reasons for Unmyelinated Axons:

  • Axons remain unmyelinated due to three key evolutionary principles:

    • Functional Advantage: Certain pathways operate optimally at lower speeds, where rapid transmission offers no physiological advantage.

    • Lack of Selective Pressure: The absence of myelin in specific axons is not disadvantageous, meaning no evolutionary pressure exists to alter the structure.

    • Energetic Cost: Myelination requires significant cellular energy to construct and maintain; unmyelinated axons conserve metabolic energy.

Cellular Mechanisms of Myelination: PNS vs. CNS

• Anatomy of Myelinated Axons:

  • Axolemma: The continuous plasma membrane surrounding the axon cytoplasm.

  • Internodes: The myelinated segments of an axon where neuroglial plasma membranes are wrapped tightly around the axolemma.

  • Nodes of Ranvier (Nodes): The unmyelinated gaps situated along the axon between adjacent internodes.

• Peripheral Nervous System (PNS) Myelination:

  • Primary Glial Cell: Schwann cells (also named neurolemmocytes).

  • Structural Arrangement:

  • An individual Schwann cell wraps its entire cell body concentrically around a single internode segment of one axon.

  • During wrapping, the cytoplasm, nucleus, and organelles of the Schwann cell are pushed entirely to the outer edge of the spiral wrap.

  • Neurolemma (spelled interchangeably as neurolemma or neurilemma): The outermost nucleated cytoplasmic layer of the Schwann cell surrounding the myelin sheath.

• Central Nervous System (CNS) Myelination:

  • Primary Glial Cell: Oligodendrocytes.

  • Structural Arrangement:

  • The main cell body of an oligodendrocyte remains separate from the axons it insulates.

  • The cell extends long cytoplasmic processes that reach out to wrap around axon segments.

  • A single oligodendrocyte extends multiple processes capable of myelinating several internodes on the same axon or across multiple distinct axons simultaneously.

• Three Major Differences Between CNS and PNS Myelination:

  • Presence of Neurolemma: Present exclusively in the PNS. Absent in the CNS because oligodendrocyte cell bodies do not wrap directly around axons.

  • Myelination Capacity: Oligodendrocytes can myelinate multiple axons or multiple segments of an axon. Schwann cells can only myelinate a single segment of a single axon.

  • Developmental Timing: PNS myelination initiates significantly earlier in development than CNS myelination.

Developmental Timeline and Life Cycle of Myelination

• Timeline of Gestation and Brain Maturation:

  • Gastrulation & Neural Tube Formation: Occurs at $3\,\text{weeks}$ of gestation.

  • PNS Myelination Onset: Initiates during the $5^{\text{th}}\text{ month}$ of gestation (e.g., cranial nerves).

  • Gestation Duration: Averages $40\,\text{weeks}$ in total.

  • CNS Brain Growth Spurt: Rapid acceleration of brain growth and central myelination occurs during the third trimester, starting at $28\,\text{weeks}$ of gestation. Adequate dietary intake of essential fatty acids is critical during pregnancy to support this lipid deposition.

  • Postnatal Myelination: Intense brain expansion and myelin sheath deposition continues throughout the first $2\,\text{years}$ of life.

• Life Cycle of Oligodendrocytes:

  • Precursor Stage: Oligodendrocyte Precursor Cells (OPCs) proliferate and differentiate. During development, a substantial portion of OPCs undergo programmed cell death.

  • Mature Stage: Surviving OPCs differentiate into mature, functional oligodendrocytes committed to producing myelin.

  • Age-Related Dynamics:

  • At Birth: Central myelination is minimal and incomplete.

  • Young Adulthood: Myelin sheath structure across CNS tracts is largely complete and fully functional.

  • Advanced Age: Aging is associated with progressive structural deterioration of oligodendrocytes and loss of myelin sheath integrity.

Clinical Pathology: Multiple Sclerosis (MS)

• Mechanisms of Autoimmune Pathology:

  • Normal Immune Selection: The immune system generates a diverse array of B cells and antibodies to recognize potential foreign antigens. Self-reactive B and T cells that recognize host antigens are destroyed during early development.

  • Autoimmune Breakdown: Dysregulation of immune tolerance leads to self-reactive lymphocytes attacking host tissues.

• Pathophysiology of Multiple Sclerosis:

  • Etiology: Autoreactive B cells fail to recognize oligodendrocytes as self-tissue, generating antibodies that target cell surface antigens on oligodendrocytes.

  • Damage: Immune-mediated attack destroys oligodendrocytes, resulting in progressive demyelination of CNS axons.

  • Physiological Impact: Destruction of the myelin sheath disrupts or blocks action potential (impulse) conduction along affected axons. Signals arrive at the receptive region of the neuron but cannot be conducted along the demyelinated axon.

  • Demographics: MS occurs more frequently in women due to sex-specific differences in immune regulation and X-chromosome inactivation. Onset typically occurs in middle to late adulthood.

  • Clinical Manifestations: Neurological symptoms include tingling, numbness, severe headaches, cognitive dysfunction, and dizziness.

Questions & Discussion

• Question: How can a myelinated axon cross-section be identified as belonging to the PNS rather than the CNS?

  • Answer: By examining the physical structure of the myelinating cell. In the PNS, the entire Schwann cell body wraps around a single axon segment, pushing its nucleus and cytoplasm to the outer edge to form a distinct neurolemma. In the CNS, oligodendrocyte cell bodies remain separate from axons and use long projections to insulate multiple axons without forming a outer neurolemma layer.

• Question: What allows structural distinction between multipolar, bipolar, and pseudo-unipolar neurons?

  • Answer:

  • Multipolar neurons feature numerous dendrites and a single axon extending directly from the cell body.

  • Bipolar neurons feature two distinct processes (one dendrite and one axon) extending from opposite poles of the cell body.

  • Pseudo-unipolar neurons feature a single short process leaving the cell body that splits into two extended axon branches.