APHY 101 10.2

Overview of Nervous Tissue Cells

  • Cellular Origins and Relationships:

    • Neurons and neuroglia are the two primary cell types constituting nervous tissue.

    • Both neurons and neuroglia descend from the same neural stem cells.

    • They remain closely associated structurally and functionally throughout their existence.

  • Relative Abundance:

    • Neuroglia outnumber neurons by a ratio of 10:110:1.

    • Neuroglia comprise more than half of the total brain volume.

Structure of Neurons

Structure of a typical multipolar neuron

  • General Features:

    • All neurons share three fundamental structural components: a cell body, dendrites, and an axon.

    • Neurons demonstrate significant variation in size and shape, process numbers, and the lengths and sizes of their axons and dendrites.

    • The universal direction of nerve impulse flow is receipt of input at dendrites and cell body, followed by output transmission conducted away from the cell body down the axon.

  • Cell Body (Soma or Perikaryon):

    • Nucleus: Contains a large, spherical nucleus positioned near the center with a prominent, conspicuous nucleolus.

    • Cytoplasm: Contains granular cytoplasm rich in cellular organelles including mitochondria, lysosomes, a Golgi apparatus, and microtubules.

    • Neurofilaments: A network of fine protein threads that extends into the axon to provide structural support.

    • Chromatophilic Substance (Nissl Bodies): Membranous packets scattered throughout the cytoplasm consisting primarily of rough endoplasmic reticulum (RER).

    • Cytoplasmic Inclusions: Storage granules within the soma including glycogen, lipids, and cellular pigments such as melanin.

  • Dendrites:

    • Highly branched processes that function as the primary receptive surfaces for receiving signals from processes of other neurons.

    • In certain neuron types, the cell body surface also functions as a receptive site.

    • Dendritic Spines: Tiny, thorn-like projections covering dendrite surfaces that act as specialized contact sites for synaptic connections.

  • Axons:

    • Each neuron possesses at most one axon (some may have none, but never more than one).

    • Axon Hillock: A cone-shaped elevation on the cell body from which the axon originates.

    • Axoplasm Organelles: Contains abundant mitochondria, microtubules, and neurofibrils. Ribosomes are absent in the axon and are restricted to the cell body.

    • Collaterals: Branch structures given off along the length of an axon.

    • Axon Terminals: Fine arborized extensions at the distal terminus of an axon.

    • Synaptic Knob: Expanded terminal swelling at the end of an axon terminal that sits adjacent to a target cell's receptive surface.

    • Synaptic Cleft: The narrow extracellular gap separating the synaptic knob from the receptive membrane of the target cell.

    • Axonal Transport:

      • A highly regulated bidirectional transport system that moves biochemicals and organelles between the cell body and axon terminals.

      • Anterograde Transport: Moves materials from the cell body to axon terminals (e.g., enzymes required for neurotransmitter synthesis).

      • Retrograde Transport: Moves materials from axon terminals back to the cell body (e.g., old organelles and cellular components designated for recycling).

  • Axon Bundles:

    • Axons within the nervous system travel together in organized groups.

    • Nerves: Bundles of axons located in the Peripheral Nervous System (PNS).

    • Tracts: Bundles of axons located in the Central Nervous System (CNS).

  • Myelination and Schwann Cells:

    • In the PNS, neuroglia called Schwann cells (neurolemmocytes) encase large peripheral axons in lipid-rich sheaths.

    • Myelin: Made of tightly wrapped layers of Schwann cell membrane containing multiple types of lipids and proteins. This composition gives the membrane a significantly higher proportion of lipids than typical cell membranes.

    • Myelin Sheath: The multi-layered insulating lipid wrapping directly surrounding the axon.

    • Neurilemma (Neurilemmal Sheath): The outermost layer of the Schwann cell surrounding the myelin sheath, containing most of the cell's cytoplasm and its nucleus.

    • Nodes of Ranvier (Myelin Sheath Gaps): Narrow, uninsulated gaps in the myelin sheath located between adjacent Schwann cells along the length of the axon.

Diagram of a myelinated axon showing the myelin sheath, neurilemma, and nodes of Ranvier

  • Unmyelinated Axons:

    • Small peripheral axons are enclosed by Schwann cells but are not wrapped in multiple lipid layers, lacking a myelin sheath.

    • Unmyelinated axons sit partially or completely within longitudinal grooves formed by enveloping Schwann cells.

Transmission electron micrograph showing cross sections of myelinated and unmyelinated axons

  • White Matter vs. Gray Matter:

    • White Matter: Composed of dense aggregations of myelinated axons in the CNS, obtaining its white appearance from the high lipid content of myelin sheaths.

    • Gray Matter: Composed of unmyelinated nerve fibers, dendrites, and neuron cell bodies within the CNS.

    • CNS Myelination: Produced by oligodendrocytes rather than Schwann cells. Myelinated axons in the CNS lack neurilemmae.

    • Additional Glial Functions: Both Schwann cells and oligodendrocytes participate in axonal energy metabolism, regulation of axon diameter, and structural organization of ion channels at the nodes of Ranvier.

Clinical Applications

  • Multiple Sclerosis (MS):

    • Epidemiology: Affects approximately 2.5 million2.5\text{ million} individuals worldwide, including 400,000400{,}000 in North America. Symptom onset typically occurs between ages 2020 and 4040 (70%70\% of cases), with the youngest recorded onset at 3 years3\text{ years} and oldest at 67 years67\text{ years}. Females are twice as likely to develop MS as males. It occurs with higher prevalence in Caucasians and in temperate geographic zones (Europe, North America, South America).

    • Pathophysiology: An autoimmune disease triggered when peripheral T cells cross the blood-brain barrier and initiate an inflammatory cascade against CNS myelin. T cells release inflammatory cytokines and recruit cells that produce autoantibodies against myelin proteins. Destruction of myelin leaves hardened scar tissue called scleroses, which blocks or impairs nerve impulse conduction, leading to muscle disuse and atrophy.

    • Clinical Presentation: Symptoms include blurred or double vision, limb weakness, numbness, impaired motor coordination, fatigue, mood disorders (e.g., depression), and potential permanent paralysis.

    • Disease Subtypes: Four distinct subtypes exist, with the most common being:

      • Relapsing-Remitting: Characterized by discrete symptomatic flare-ups followed by periods of partial or full recovery.

      • Secondary Progressive: Characterized by continuous, non-abating accumulation of neurological disability.

    • Diagnostic Tools: Clinical evaluation, repeated magnetic resonance (MR) scans to track lesion progression, lumbar puncture (to exclude CNS infection), and evoked potential testing (measuring cerebral electrical responses to sensory stimuli).

    • Pharmacological Treatments:

      • Symptomatic Management: Antispasmodics for bladder dysfunction, muscle relaxants for spasticity, antidepressants, and short-term corticosteroid bursts to shorten acute relapses.

      • Beta Interferons: Injectable immune modulators administered 1 to several times per week that reduce relapse frequency (side effects include flu-like symptoms).

      • Glatiramer: Daily self-injected drug formulated with synthetic peptides mimicking myelin basic protein (the most abundant protein in myelin); shifts T cells to an anti-inflammatory phenotype and increases secretion of brain-derived neurotrophic factor to preserve axons.

      • Mitoxantrone: Potent immunosuppressive agent reserved for severe MS due to cardiotoxicity risks; clinical administration is capped at a maximum duration of 2 years2\text{ years}.

      • Natalizumab: Monoclonal antibody that prevents T cell adhesion and migration across brain vascular endothelium.

    • Experimental Therapies:

      • Personalized T Cell Immunotherapy: Directs immune responses specifically against autoreactive myelin-directed T cells.

      • Autologous Bone Marrow Transplantation: Ablates and reconstitutes the immune system to remove myelin-reactive T cell clones. Promises long-term remission (>10 years>10\text{ years}) in relapsing-remitting disease.

      • Adipose-Derived Stem Cells: Evaluation of autologous mesenchymal stem cell delivery.

  • Adrenoleukodystrophy (ALD):

    • A metabolic disorder leading to progressive demyelination within the brain and spinal cord of affected males.

Structural and Functional Classification of Neurons

Structural types of neurons including multipolar, bipolar, and unipolar neurons

  • Structural Classification:

    • Multipolar Neurons:

      • Structure: Possess a single axon and numerous highly branching dendrites extending from the cell body.

      • Location: Predominant structural type within the brain and spinal cord; also present in autonomic ganglia and specialized structures of the eye.

    • Bipolar Neurons:

      • Structure: Cell body has two distinct processes originating from opposite poles—one acting as an axon and the other as a dendrite.

      • Location: Restricted to specialized sensory regions of the eyes, ears, and olfactory mucosa of the nose.

    • Unipolar Neurons (Pseudounipolar):

      • Structure: Feature a single process arising from the cell body that branches into two functional divisions acting together as a single axon:

        • Peripheral Process: Extends to peripheral structures, ending in receptive dendrites.

        • Central Process: Traverses into the brain or spinal cord.

      • Development: Arise embryonicly as bipolar cells whose two processes fuse into a single stalk near the cell body.

      • Location: Cell bodies cluster in sensory ganglia of the PNS.

Functional relationships among sensory neurons, interneurons, and motor neurons

  • Functional Classification:

    • Sensory Neurons (Afferent Neurons):

      • Function: Transmit sensory impulses from peripheral sensory receptors into the CNS.

      • Receptors: Dendritic endings or associated structures detect changes in the external environment (light, sound, cutaneous touch) or internal environment (body temperature, arterial blood pressure).

      • Structural Type: Predominantly unipolar, though some are bipolar or multipolar.

    • Interneurons (Association or Internuncial Neurons):

      • Function: Located entirely within the CNS; process, integrate, and route incoming sensory data to specific CNS centers and relay motor instructions to motor neurons.

      • Structural Type: Multipolar.

      • Nuclei: Aggregations of interneuron cell bodies within the CNS (equivalent to PNS ganglia).

    • Motor Neurons (Efferent Neurons):

      • Function: Carry nerve impulses out of the CNS to effector organs (muscles or glands).

      • Somatic Motor Neurons: Control voluntary skeletal muscle contraction.

      • Autonomic Motor Neurons: Regulate involuntary effectors including smooth muscle, cardiac muscle, and exocrine/endocrine glands.

      • Structural Type: Multipolar.

Neuroglia (Glial Cells)

  • General Functions of Neuroglia:

    • Provide structural scaffolding and positioning for neurons during embryonic development.

    • Induce neuronal differentiation and specialization through trophic signaling.

    • Secrete neurotrophic factors that sustain neuron survival.

    • Maintain homeostatic ion concentrations (e.g., K+K^+) in extracellular fluids.

    • Clear excess neurotransmitters from synaptic spaces.

    • Stimulate synapse formation and maintenance (specifically astrocytes and Schwann cells).

Types of neuroglia found in the central nervous system

  • Neuroglia of the Central Nervous System (CNS):

    • Astrocytes:

      • Structure: Star-shaped cells with numerous elaborate cellular processes.

      • Location: Positioned between blood capillaries and neurons.

      • Functions: Provide mechanical support; regulate interstitial ion levels (e.g., potassium ions); facilitate glucose metabolism; transport nutrients and metabolites between capillaries and neurons; form the blood-brain barrier via perivascular end-feet; synthesize growth factors; form glial scar tissue following CNS injury; communicate via gap junctions using inter-astrocytic calcium (Ca2+Ca^{2+}) waves.

    • Oligodendrocytes:

      • Structure: Morphologically similar to astrocytes but smaller with fewer, shorter processes; align in rows along axons.

      • Functions: Form myelin sheaths around CNS axons; a single oligodendrocyte extends multiple flattened processes to myelinate segments of several adjacent axons simultaneously; secrete nerve growth factors; do not form neurilemmae.

    • Microglia:

      • Structure: Small cells with sparse, branched processes.

      • Functions: Act as resident CNS macrophages; perform phagocytosis to clear bacterial pathogens, dead cells, and cellular debris; proliferate rapidly during CNS infection, trauma, or inflammation.

    • Ependyma:

      • Structure: Cuboidal or columnar cells, frequently bearing cilia (cilia are motile during embryogenesis and childhood, becoming localized primarily to cerebral ventricles in adults).

      • Location: Line the central canal of the spinal cord and the ventricles of the brain; cover choroid plexuses.

      • Functions: Form a porous epithelial-like membrane allowing continuous fluid exchange between brain parenchyma interstitial fluid and cerebrospinal fluid (CSF); joined by gap junctions; regulate CSF chemical composition at choroid plexuses.

Neuroglia found in the peripheral nervous system including satellite cells and Schwann cells

  • Neuroglia of the Peripheral Nervous System (PNS):

    • Schwann Cells (Neurolemmocytes):

      • Functions: Produce lipid-rich myelin sheaths around peripheral axons; enclose unmyelinated axons in longitudinal grooves; clean up excess extracellular ions and neurotransmitters; guide axonal regeneration post-injury.

    • Satellite Cells:

      • Structure: Small, cuboidal cells surrounding neuron cell bodies.

      • Location: Within sensory and autonomic ganglia of the PNS.

      • Functions: Provide structural and metabolic support; buffer ionic concentrations in the microenvironment of ganglionic soma.

  • Neuroglial Involvement in Pathology:

    • Brain Tumors: Most adult primary brain tumors (gliomas) originate from neuroglia that undergo uncontrolled cell division.

    • Amyotrophic Lateral Sclerosis (ALS / Lou Gehrig's Disease): In familial forms, dysfunctional astrocytes release neurotoxic molecules that selectively destroy motor neurons, leading to progressive muscle paralysis.

    • Huntington Disease (HD): Hyperactive microglial activation releases inflammatory cytokines and cytotoxins, driving neuronal degeneration in the brain.

Axonal Regeneration

  • Cell Body Injury:

    • If a neuron's cell body is destroyed, the neuron dies permanently and is not replaced, as mature neurons lose mitotic capacity.

    • Neurogenesis is restricted to specific stem cell niches containing neural stem cells that yield neural progenitor cells.

  • Peripheral Axon Regeneration Process:

    1. Axonal Injury: Division or severe compression separates a segment of a peripheral axon from its soma.

    2. Wallerian Degeneration: The axon portion distal to the injury site and its myelin sheath break down and degenerate within a few weeks.

    3. Debris Clearance: Macrophages migrate to the site and phagocytize myelin and axonal fragments; the outer neurilemmal tube and surrounding Schwann cells survive intact.

    4. Sprouting: The surviving proximal axon segment forms multiple terminal sprouts under the influence of neurotrophic factors secreted by neuroglia.

    5. Regeneration Tube Formation: Schwann cells proliferate along the original path, forming a hollow regeneration tube that directs a growing axonal sprout toward its target.

    6. Elongation and Remyelination: Axonal sprouts grow through the Schwann cell tube at a rate of up to 4 mm/day4\text{ mm/day}. Schwann cells wrap the regenerating axon with new myelin sheaths.

    7. Functional Recovery: If the sprout successfully re-establishes connections with its original target effector or receptor, function is restored. Mismatched target connections result in incomplete functional recovery.

  • Central Axon Regeneration Deficits:

    • Axons separated from cell bodies within the CNS degenerate slowly.

    • Regeneration fails in the CNS due to key structural differences:

      • CNS axons lack neurilemmae.

      • Oligodendrocytes do not proliferate post-injury and collapse rather than forming guiding tubes.

      • Astrocytes form dense scar tissue (gliosis) that physically inhibits axonal growth.

      • CNS glial cells express myelin-associated inhibitory proteins that halt axonal extension.

Questions & Discussion

  • Practice Question 10.3:

    • Question: The genes in the nucleus of a neuron are the same as the genes in the nuclei of its Schwann cells. What causes these cells to have such different form and function?

    • Answer: Cellular differentiation.

  • Practice Review Questions 10.2:

    • Question 1: Describe a neuron.

    • Answer: Neurons vary in size and shape, but each has a cell body, input processes called dendrites, and an output process called an axon. Neurons may also be associated with certain neuroglia that form myelin.

    • Question 2: Explain how an axon in the peripheral nervous system becomes myelinated.

    • Answer: In the PNS, neuroglia called Schwann cells encase axons of certain peripheral neurons in layers of cell membrane filled with a fatty material called myelin, to form myelin sheaths. A myelin sheath is an electrical insulator for myelinated axons.

    • Question 3: Describe the types of neurons based on structural characteristics.

    • Answer: Neurons are classified structurally as multipolar (having many processes arising from the cell body, one axon and many dendrites), bipolar (having two processes, one axon and one dendrite), or unipolar (having a single process extending from the cell body that divides into a peripheral branch and a central branch).

    • Question 4: Indicate the function of sensory neurons, interneurons, and motor neurons.

    • Answer: Sensory neurons conduct impulses from peripheral body parts into the brain or spinal cord. Interneurons relay information between neurons within the CNS. Motor neurons conduct impulses out of the brain or spinal cord to effectors such as muscles or glands.

    • Question 5: Name and describe six types of neuroglia.

    • Answer: The four types of neuroglia of the CNS are microglia, oligodendrocytes, astrocytes, and ependymal cells. Microglia are tiny cells that perform phagocytosis of bacteria and debris. Oligodendrocytes produce the myelin sheath around CNS axons to increase conduction speed. Astrocytes regulate nutrient and ion levels, provide structural support, and maintain the blood-brain barrier. Ependymal cells line brain ventricles and the spinal cord central canal, helping produce and regulate cerebrospinal fluid. The two types of neuroglia in the PNS are Schwann cells (which form myelin sheaths around peripheral axons) and satellite cells (which surround and support cell bodies in ganglia).

    • Question 6: What are some functions of neuroglia?

    • Answer: Functions of neuroglia include producing the myelin sheath around certain axons, providing structural and nutritional support for neurons, forming scar tissue, performing phagocytosis, taking up excess ions and neurotransmitters, exchanging substances between blood vessels and neurons, supporting neuron regeneration in the PNS, helping form and regulate cerebrospinal fluid in the CNS, and facilitating synapse formation and maintenance.