ELM 22 Neuropathology Flashcards
What are synaptopathies?
Synaptopathies are brain disorders that have arisen from synaptic dysfunction, which can include problems in neurotransmitter synthesis/release, issues with vesicle machinery, and problems in signaling, expression, and functioning of postsynaptic receptors.
How do changes in dendritic spines affect synaptic function?
Changes in dendritic spines affect synaptic function. For example, long-term potentiation (LTP) increases spine size, while long-term depression (LTD) decreases spine size. Spine size correlates with postsynaptic density, the number of glutamate receptors, and synaptic strength, and is linked to synaptic plasticity, learning, and memory.
What are the consequences of synaptopathies?
Consequences of synaptopathies include abnormal density and morphology of synapses, aberrant signaling and plasticity, synapse loss, and neuronal death. These can result from various factors such as genetics, drugs, aging, and viral infections.
What is epilepsy?
Epilepsy affects approximately 50 million people worldwide and is characterized by the occurrence of epileptic seizures, which involve uncontrolled and excessive synchronized electrical activity of central neurons. The cause of epilepsy is often unknown, but factors such as infection, stroke, and traumatic brain injury can increase susceptibility.
How is epilepsy treated?
Treatment for epilepsy typically involves anti-convulsant and antiepileptic drugs (AEDs). For example, levetiracetam reduces neurotransmitter release at glutamatergic synapses, valproate increases the amount of inhibitory GABA, and phenytoin prolongs the inactivation of sodium channels.
What are some forms of epilepsy that are inherited?
Some forms of epilepsy are inherited and can be traced to mutations in ion channels, such as mutations in subunits of GABAA receptors, voltage-gated potassium, sodium channels, chloride channels, and neurol nAChRs (neuronal nicotinic acetylcholine receptors).
What are ion channels?
Ion channels are protein molecules that span the cell membrane, allowing the passage of ions from one side to the other. They include voltage-gated channels and ligand-gated ion channels and play a critical role in controlling neuronal excitability.
What are channelopathies?
Channelopathies are a group of disorders resulting from dysfunction of ion channels, often of genetic or autoimmune origin. They can lead to various conditions such as different types of epilepsy, migraine, ataxia, and paralysis.
How do abnormalities in potassium and calcium channels in the brain contribute to channelopathies?
Abnormal potassium and calcium channels in the brain can lead to repolarization defects, resulting in convulsions. Dysfunction of these channels affects the balance of ions across the cell membrane, leading to abnormal neuronal excitability.
What is the role of GRIN2B mutations in channelopathies?
GRIN2B mutations involve the gene encoding NR2B, which is the beta-2 subunit of the NMDA receptor, a ligand-gated ion channel that binds glutamate. Gain-of-function mutations can lead to hyperexcitability and seizures, while loss-of-function mutations can cause hypoexcitability, leading to learning difficulties and neurodevelopmental problems.
What is Myotonia Congenita (MC), and what animals does it affect?
Myotonia Congenita (MC) is a type of channelopathy found in animals, such as fainting goats. It causes muscles to sometimes fail to relax after contraction, leading the affected animals to keel over. In goats, it is often triggered by excitement or being startled.
What is the genetic mutation associated with Myotonia Congenita (MC)?
Myotonia Congenita (MC) is associated with a mutation in the skeletal muscle chloride channel, CLCN1. This mutation leads to the characteristic muscle stiffness and difficulty in relaxation observed in affected animals and humans.
What is malignant hypothermia, and what triggers its occurrence?
Malignant hypothermia is a condition characterized by attacks of hyperactivity in muscle cells, resulting in rigid muscles, high fever, and increased heart rate. It occurs in response to specific triggers such as general anesthesia and exercise, which can lead to excessive release of calcium from the sarcoplasmic reticulum (SR) in muscle cells.
What are the potential consequences of untreated malignant hypothermia?
Untreated malignant hypothermia can lead to rhabdomyolysis (breakdown of muscle tissue) and high blood potassium levels, which can be fatal if not addressed promptly. However, most individuals with malignant hypothermia can lead a normal life if they avoid known triggers that can induce an episode.
What are the three main types of glial cells found in the brain, and what are their functions?
The three main types of glial cells in the brain are astrocytes, microglia, and oligodendrocytes. Astrocytes provide neuroprotection and support, microglia are involved in immune response and surveillance, and oligodendrocytes form myelin sheaths around axons to facilitate signal transmission.
