Brain cells

Golgi: Reticular theory

• Revealed two parts of neurons:

  • Cell body

  • Neurites e.g. axons and dendrites

Cajal: Neuron Doctrine

• Neurons are distinct cellular units

• Can be studied through ‘double-impregnation’ with silver nitrate

Neuron

• Receives, integrates and transmits information through electrical and chemical signalling

• Senses detailed environmental changes

• Communicates detailed changes to other neurons

• Coordinates bodily response

• Around 85 billion in an adult human

Soma

• Around 20 micrometres

• Metabolic centre of the neuron

• Consists of cytoplasm, cytosol and organelles e.g. nucleus, reticuli and mitochondria

Cytoplasm

Everything inside the cell membrane including organelles, excluding the nucleus

Cytosol

Intracellular fluid inside a cell

• Salty, potassium-rich solution

Organelles

Same as found in other eukaryotic cells

• e.g. nucleus, mitochondria, rough endoplasmic reticulum, smooth endoplasmic reticulum

Neural DNA sequence

• Transcription → mRNA → Transcription → Protein

• e.g. receptors and ion channels are proteins influencing neuronal signalling

• Neurons differ from other cells due to a specific subset of genes

• Genetic basis of many diseases of the nervous system e.g. Huntingtons

Endoplasmic reticular differences

• Rough ER - Protein production and processing

• Smooth ER - Lipid production and calcium regulation

Translation

• mRNA bind to ribosomes to translate mRNA into proteins

• Many ribosomes are attached to the rough ER

• Golgi apparatus - proteins and lipids made in the ER are modified and sorted

Gene editing in brain research

• Important tool for brain research and understanding and treating nervous system disorders

• Basic utilities:

  • Correcting inherited disorders

  • Halting disease progression

  • Simulating diseases for scientific discovery

  • Overcoming delivery challenges

Gene editing: Correcting inherited disorders

• Many brain diseases are monogenic (caused by a mistake in a single gene)

• By using precision genome editing tools like CRISPR, researchers can cut out toxic insertions or repair mutations that destroy neurons

• e.g. repeat mutations in Huntington’s disease

Transcription

• DNA - Contains building plan for all cells in the body

• DNA acts as a blueprint for RNA → like a photo negative

• mRNA exits nucleus, carrying coding information

• Cells express different combinations and levels of genes as a result

Gene editing: Halting disease progression

• Traditional medications only manage the symptoms of brain diseases (e.g. reducing tremors or eassing pain)

• Gene targeting goes for the biological root cause, allowing doctors to potentially stop progressive degeneration before permanent brain damage occurs

Gene editing: Simulating diseases for scientific discovery

• Scientists use genetic engineering to create animal models that mimic human brain diseases

• By introducing specific mutations into these models, researchers can closely observe how diseases like AD unfold in living tissue and test new therapies safely

Gene editing: Overcoming delivery challenges

• Brain protected by the blood-brain barrier, blocking most standard drugs from entering

• Precision genetic technologies allow scientists to engineer harmless viruses or specialised nanoparticles to carry therapeutic DNA changes directly to affected brain cells

Soma

Consists of mitochondria, cytoskeleton and neuronal membrane

Mitochondria

• Responsible for cellular membrane, generating ATP

• ATP is the energy currency of the cell

Cytoskeleton

• ‘cell skeleton’

• Cell shape

• Correct positioning of organelles - not static

• Tracks for in-cell transportation

Neuronal membrane

• Barrier to enclose the cytoplasm inside the neuron

• Protein composition varies depending on the location (soma, axon, dendrites)

• Structure of discrete membrane regions influences neuronal functions

Axon

• Consists of axon hillock (beginning), axon proper (middle) and axon terminal (end)

• Only found in neurons, each only having one axon

• Highly specialised for information transfer (electrical signals) over distances (electrical cables)

• No rough ER, hardly any ribosomes - little protein synthesis in axon, most of proteins in axon come from soma

• Axons can extend <1mm to 1m long

Axon hillock

Region where the axon originates

• Neurofilaments in the axon hillock become clustered together as fascicles

Axoplasmatic transport

Ensures necessary material travels from the soma to the axon terminal (anterograde transport) and back (retrograde transport)

Differences between axon and soma

• ER does not extend into axon

• Unique protein composition

Terminal bouton

• Region where axon contacts with other neurons

• No microtubules in the terminal

• Synaptic vesicles - contain important chemicals for communication (neurotransmitters)

• Numerous mitochondria due to high energy demand

Synapse

Electrical signal → chemical signal → electrical signal

• Synaptic transmission dysfunction

  • Brain and muscle disorders

  • Action site for toxins and psychoactive and therapeutically useful drugs

Dendrite

• ‘Antennae’ of neurons

• Dendritic tree

• Synapse-receptors

Postsynaptic membrane

• Full with receptors - special proteins that bind to NTs

• Take up chemical signals from pre-synaptic neuron and carry on electrical signals

Dendritic spines

Small protrusions of membrane that receive signals from the axon terminal.

• Increase possible synaptic contact sites between neurons

• Effective synapses that can quickly change in appearance

• Important for plasticity and learning (new spines can grow, existing spines can become larger or smaller)

Brainbow - Imaging technique

• Labels each nerve cell a different colour to identify and track axons and dendrites over long distances

• Scientists can use light microscopy to image branching patterns and connections of all axons within a region of the NS, expressing a number of different proteins in individual neurons

Neural classification

• Neurons differ from other cells due to being a subset of genes

• Genetic basis og many diseases in the NS

• Classification can be based on gross anatomy, dendritic morphology, or number of neurites

Classification: Neurites

• Classification based on number of neurites

• Unipolar: One neurite

• Bipolar: Two neurites

• Multipolar: More than two neurites

• Neurite = axons + dendrites

• Uni- and bipolar neurons most often sensory as they take up a smaller amt of info, leading to greater precision

Classification: Morphology

• Stellate cells (star shaped) and pyramidal cells (pyramid shaped)

• Cerebral and cerebellar cortex have different types of stellate cells

• Spiny or aspiny

Stellate cells

• Tight network of dendrites

• Perfect for interconnection and info exchange between neighbouring neurons

Pyramidal cells

• Dendrite tree, similar shape to a pyramid, with a long axon

• Perfect for transfer of info over long distances

Classification: Gross anatomy

• CNS connections: primary sensory neurons, motor neurons and interneurons

• Axonal length: Golgi type I - projection neurons, Golgi type II - local circuit neurons

• intrinsic physiology: Intrinsic physiology roughly similar, physiological details differ

Glial cells

• Regulate the environment

• Provide metabolic and immune support

• Influence neuronal communication

Glial cells: Astrocytes

• Most abundant neuroglia in the brain

• Found in gaps between neurons, influencing neurite growth

• Regulate chemical content in extracellular space (K+)

• Restrict spread of NTs from synaptic cleft

• Actively remove NTs from synaptic cleft

• Trigger electrical and biochemical events inside the glial cell

Microglia

• 10% of brain cells

• Immune first responders

• Housekeepers of the brain

• Act as phagocytes, removing debris left by dead or degenerating cells in both healthy and diseased brains

• Conduct synaptic pruning

• Reactive gliosis and neuroinflammation are symptoms of Alzheimer’s DIsease

Oligodendrocytes

Myelinate segments of several axons

• Located in the CNS

Schwann cells

Wraps one segment of the axon

• Located in the PNS

Role of myelin

• lipid-rich sheath wrapped around axons, insulates and increases conduction speed

• When it is damaged, nerve conduction becomes slower or may fail

Multiple Sclerosis: CNS changes

• Immune-mediated inflammation damages CNS myelin and may injure axons

• Lesions can occur in the brain, optic nerves and spinal cord

• MS can involve axonal injury and neurodegeneration , not only myelin loss

Symptoms of MS

• Visual disturbance

• Weakness or altered sensation

• Balance and coordination difficulties

• Fatigue and cognitive difficulties

• Symptoms depend on which CNS pathways are affected