Neurons: Cell Body/Soma & Dendrites

• Neurons: The functional unit of both the central and peripheral nervous systems

Cell Body/Soma

• Contains the nucleus and most of the cell's organelles
• Responsible for most of the cytoplasm production for nerve processes
• Receives excitatory or inhibitory stimuli from numerous nerve endings of other neurons
• Cytoplasm features free polyribosomes and developed RER, which actively create cytoskeletal and transport proteins
• Contains basophilic regions called chromatophilic substance that varies based on the neuron's type and function
• Abundant in large nerve cells like motor neurons
• The Golgi apparatus is only in the cell body, whereas mitochondria are throughout the cell, especially in axon terminals
• Contains an abundance of actin and intermediate filaments composed of neurofilaments/proteins

Dendrites

• Processes (branches) extending from the cell body that receive stimuli at synapses
• Have many synapses for signal reception and processing
• A large number enables nerves to receive numerous signals from other nerve cells (up to 200k axon endings can connect with the dendrites of another neuron body)
• In the CNS, dendrite synapses occur on dendritic spines (DS), small dendritic branches with membrane protrusions
• DS serve as initial processing sites for synaptic signals and occur in large numbers
• They depend on actin filaments and continuously change based on synaptic connections
• Changes in DS are linked to neural plasticity during brain development (embryo), adaptation, learning, and memory

Axons

• Single long process (trunk) that conducts nerve impulses to other cells
• Receives information from other cells, modifying action potential transmission
• Length and diameter depend on the neuron type
• Motor neurons innervating foot muscles are nearly a meter long
• Long cell bodies are needed to maintain axons with extensive cytoplasm
• Axolemma is the axon's plasma membrane, made of axoplasm
• Originates from the axon hillock of the cell body

Sensory Neurons

• Afferent, receiving stimuli from receptors throughout the body

Motor Neurons

• Efferent, sending impulses to effector organs (muscle fibers + glands)

Somatic Motor Nerves

• Under voluntary control, innervating skeletal muscle

Autonomic Motor Nerves

• Under involuntary or unconscious control, innervating cardiac muscle, glands, and most smooth muscles

Interneurons

• Create relationships among neurons, resulting in networks or circuits
• Can be multipolar or anaxonic

Glial Cells

• Supportive cells 10x more abundant than neurons
• In the CNS, they surround cell bodies, axons, and dendrites (except blood vessels)

Oligodendrocytes

• (oligo: few, dendron: tree, kytos: cell)
• Extend numerous sheetlike processes that wrap around nearby CNS axons
• Form a myelin sheath covering axons, which supports the action potential of oligodendrocytes
• Are the predominant glial cell in white matter
• Have a high lipid concentration in the sheaths and only in the CNS

Astrocytes

• (Astro: star, kytos: cell)
• Long, star-like radiating, branching processes
• Communicate directly with other glial cells through gap junctions to create a network regulating activity in various brain regions
• Proximal regions are reinforced with intermediate filaments made of GFAP (glial fibrillary acid protein)
• A marker for glial cells identifiable under a microscope
• Originate from the embryonic neural tube and the most abundant glial cell in the brain which are structurally & functionally diverse
  • Fibrous astrocytes: long, delicate processes abundant in white matter,
  • Protoplasmic astrocytes: short processes abundant in gray matter
• Function in the CNS regions:
  • Extend processes covering synapses, which results in changes to formation, function, and plasticity
  • Regulate extracellular ionic concentration around neurons (buffering K+ levels)
  • Guide and physically support neuron movements and locations in CNS development
  • Form a barrier layer of expanded protoplasmic processes next to the external CNS meninges (= glial limiting membrane)
  • Fill tissue defects after injury, creating astrocytic scars

Ependymal Cells

• Line brain's fluid-filled ventricles and the spinal cord's central canal that are columnar or cuboidal
• The apical end features cilia (CNS) that aid CSF movement and long microvilli that help absorption
• Joined apically by apical junctional complexes, like epithelial cells, the basal ends are elongated and extend branching processes into the nearby neuropil

Microglia

• Small cells with active moving processes evenly distributed in gray and white matter
• Processes scan the neuropil and remove damaged synapses or components
• Act as a primary mechanism of immune response in the CNS: removing microbial invaders and secreting immunoregulatory cytokines
• Originate from blood monocytes, like macrophages and antigen-presenting cells

Schwann Cells

• Exclusively in PNS and form myelin sheaths, similar to oligodendrocytes
• Form a sheath cell around a portion of axons
• Enable faster action potential propagation along the axon in the PNS

Satellite Cells of Ganglia

• Thin, intimate glial layer around neuronal cell body in ganglia of the PNS
• Insulate, nourish, and regulate micro-environments of the neuron

Blood-Brain Barrier (BBB)

• Regulates substance movement from the blood to CNS tissues
• Protects neurons against bacterial toxins, infectious agents, and other exogenous substances, maintaining constant ion balance in interstitial fluid
• Absent in the hypothalamus (plasma components are monitored), posterior pituitary (hormones are released), and choroid plexus (CSF is made)
• Capillary endothelium is a main component that tightly seals cells with occluding junctions (little to no transcytosis) and is surrounded by a basement membrane
• • The basement membrane is enveloped by the perivascular astrocytic feet further regulates the molecules and ions that go from the blood to the brain

Choroid Plexus

• Removes water from the blood and releases it as the CSF, which is clear, contains NA+, K+, CL-, very little protein, and few lymphocytes
• CSF is continuously produced and fills ventricles, the central canal of the spinal cord, the subarachnoid, and perivascular spaces
• Furnishes ions for CNS neuronal activity
• Supports in absorbing mechanical shock in the arachnoid
• Present in highly vascular tissue folded into large ventricles of the brain
• The villi feature a thin layer of vascularized pia matter covered by ependymal cells
• Found in the roof of the 3rd and 4th ventricles and parts of the 2 lateral ventricular walls

Neural Plasticity + Regeneration

• The nervous system exhibits neural differentiation and the creation of new synapses
• Apoptosis: Cells that are eliminated (self-destruction)
• Embryonic development may produce excess differentiated neurons and cells that don't make correct synapses with other neurons, eliminating them
• New communication can be established after a certain degree of functional injury
• After injury, neural circuits can be reorganized by neuronal processes, which make new synapses to replace those lost
• Controlled by factors such as neurons and glial cells from the neurotrophins family
• Injured peripheral axons have a greater chance of regeneration and function return
• The part of the axon distal to the cut or injury dedifferentiates, leading to myelin sheath shedding and phagocytosis by macrophages, which leads to muscle fibers having denervation atrophy
• Schwann cells enter the axon and form a compact cord penetrated by the regrowing axon, enabling nerve fiber regeneration and connection with the muscle fibers
• Regeneration is visible through changes in the cell body, such as chromatolysis, where the soma swells, and the nucleus migrates to a peripheral position

Specialized Connective Tissue

Cartilage

• Made of cells and extracellular matrix (ground substance and fibers)

Chondroblast

• Similar to fibroblasts, they secrete ground substance and fibers which get surrounded by substance matrix they produce

Chondrocyte

• When the matrix is made

Lacuna(e)

• Small spaces for chondrocytes in the matrix

Perichondrium

• Outer surface of cartilage made by chondroblasts
  • Made of dense connective tissue
  • Has cells resembling fibroblasts which can also make chondroblasts
  • Acts as boundary between tissues
• Appositional growth: When the cartilage becomes larger by the chondroblasts in the perichondrium creating a new cartilage matrix on the outer surface
• Interstitial growth: When cells in the core of the cartilage divide and produce chondroblasts, secreting more matrix and displacing the old cartilage, leading to expansion from inside

Hyaline Cartilage

• Most abundant, mainly on long bone surfaces in joints and as a covering cap of cartilage
• Locations include joints, trachea, bronchi, nose (tips), and ribs (ends)
• Acts as a cartilaginous precursor - becoming a future bone
  • Involved in endochondral ossification: the process of precursor cartilage transforming into bone
• Composition:
  • 60% water bounded by sulfated GAGs (chondroitin sulfate, keratan sulfate, and hyaluronan)
  • 40% collagen type II fibers, and ground substance

Fibrocartilage

• Lacks perichondrium on one end since it's not discrete tissue, thus lacking a boundary that separates tissues: begins/ends are not easily defined
• Composed of dense connective tissue and hyaline cells in a matrix
  • Connective tissue consists of fibroblasts with collagen type I fibers
• Ground substance consists of sulfated GAGs and collagen type II
• Found in vertebral discs (spinal cord), tendon junctions with long bones, and areas where greater resistance to compression and stretching is needed

Elastic Cartilage

• Matrix has elastic fibers and collagen type II fibers
• Found in flexible parts: external ear and epiglottis (in the larynx, closing during swallowing)

Bone

• Tissue made of cells and mineralized extracellular matrix
  • Inorganic portion is hydroxyapatite: made of phosphate and calcium
• Bone anatomy:
  • Light area: Compact bone
  • Dark area: Spongy bone
  • Black area: No density or bone

Types of Bone Tissue

• Lamellar (light area): Found on the surface of the bone
• Spongy, cancellous, trabecular (dark area): Appears honeycomb inside of the bone

Long Bones

• Diaphysis: Long middle part of the bone
  • Hollow in adults with an area with the least density containing yellow marrow composed of white fat
  • In infancy, it is filled with spongy bone containing red marrow- a blood-forming tissue designated as hemopoietic
• Epiphysis: Two knobby ends on either end of the diaphysis
  • Red marrow is found in both adults and irregular bones
• Epiphyseal Line: a trace back of the growth plate which facilitated bone lengthening
• Periosteum: A dense irregular connective tissue covering the external surface of bone
  • Sharpey fibers (collagen type I) connect periosteum to bone forming part of the bone matrix and serve as muscle attachment sites
• Tendons attach muscle to bone
  • 1. Is made of Collagen Type I Fibers which have interwoven onto the periosteum
  • 2. Periosteum fibers penetrate into the bone continuum of collagen fibers from muscles into the bone

Bone Chemical Composition

• Organic:
  • Matrix of bone is osteoid made Collagen type I (60%) and Ground substance (40%)
• Inorganic:
  • Hydroxyapatite: Calcium and phosphate mineral helps ossification by incorporating osteoid into bone
  • Osteoblasts creates matrix vesicles (inbound vesicle) that are membrane bound that has the enzyme alkaline phosphatase

Steps of Bone Formation

• Ossification starts with accumulation of calcium phosphate, which expands the vesicle and results in a chemical reaction to create hydroxyapatite
• The vesicle membrane then ruptures beginning ossification
  • Bone formation happens only once and begins in utero, continuing until bones stop growing (20+ years)

Embryological Bone Origin

• Intramembranous Bone: the flat (dermal) of the cranium, face, and clavicles forms from embryological membranes ossified into bone composed of compact & spongy bone
• Mesenchyme 4 weeks post-conception: Migrate to where intramembranous bone will be made, aggregates to make embryological membrane, and shapes the bone 8 weeks post-conception
• The bones consists of osteoblast from mesenchyme (synthetically active cell) that secretes osteoid in the creation of spongy bone
• Blood vessels invade the developing bone tissue, leading to the formation of red marrow from embryonic stem cells residing in the spongy bone's spaces

Endochondral Bone

• Forms from a cartilaginous precursor: a tiny model of future bone
• Same mesenchymal move to embryo and shape the long bone it will be
• Differentiate into chondroblasts which make matrix in the formation of long bone 8 weeks post-conception
• Forms hyaline cartilage covered by perichondrium occurs 9 weeks after conception
• Bone growth is appositional (growth from the outer surface) and interstitial (growth from inside)
• The inner layer of periosteum differentiates into the osteoblast layer, which now becomes periosteum 10 weeks after conception
• Osteoblasts secrete osteoid that covers precursor area that is now the diaphysis and also converts it to the bony collar
• Blood vessels and mesenchymal cells move through pores. Mesenchymal cells then differentiate into osteoprogenitor cells which line the cartilaginous surface including its spicules
• Osteoprogenitor cells turn into osteoblasts and osteoid transforms into a layer of bone making a mixed spicule
• As cartilage matrix disappears replacing bone with spongy bone the process is marked by acidophilic areas (bone) basophilic regions (cartilage matrix)
• Week 39 the fetus features compact bone, spongy bone with red marrow, and the epiphysis forms

Epiphyseal Growth

• In the epiphyseal growth plate turns cartilage into bone: endochondral ossification
• Zonation: there are 5 zones

Zone 1

• Reserve cartilage, pure hyaline

Zone 2

• Proliferation, cells stacked in vertical rows

Zone 3

• Hypertrophy, cells mature and fill lacunae

Zone 4

• Degeneration, alkaline phosphate is secreted resulting calcification and cell death of cell, creating empty holes in the matrix

Zone 5

• Ossification, osteoblasts lining the holes of the new and secreting osteoid to form new one.

Secondary Ossification

• Occurs after birth and complete epiphyseal bone
• The secondary step is proximal (meaning it occurs closer to the body) that results in joints and the articular surfaces
• Width Growth: appositional and intramembranous bone

Bone Remodeling

• Involves the removal and replacement of bone
• Main cell= osteoclast, large cell with multiple nuclei
• When inactive, the cell lies on the bone surface awaiting activation but under specific controls and influences the process is actively in progress
• Influenced by parathyroid hormones, cytokines secreted by osteoclasts and enzymes made by the matrix
• Bone organic materials of fiber and osteoid consisting of GAGs dissociates with inorganic hydroxyapatite
• Acid and enzymes break down bone which results in a hole known as the Howship’s lacuna
• Osteoblasts place new layers of osteoid which creates layers of bone to make haversian canals

Muscle Tissue

• Can be classified by function as for the ability to change shape and generate a force for 3 types: skeletal, cardiac, and smooth
• Muscle fiber(cell) = myofiber
• Shaped as a cylinder and parallels others in the same muscle and is as long as the muscle itself
• Cell diameter varies based on muscle type and environment

Skeletal Muscle

• Are multinucleated or syncytium
• External lamina(sleeve) - cover skeletal cell membrane with basement membrane
• Endomysium surrounds and is made of collagen
• Sarcolemma: cell membrane and external lamina
• Sarcoplasm: cytoplasm
• Sarcoplasmic reticulum: smooth endoplasmic reticulum are not continuous nor as well are bundled that they are stacked in fragment units
• Terminal cisternae : continuous units that are hollow and contain cavity
• and
  • T-tubules - holes that project towards the cytoplasm and for branching that allows tubules to connect
• Triad: Group of 3 Closely arranged structures including triads
• Myofibril: Includes fiber (largest) + fibrils + fibrils filaments (smallest)