random things that seem importand Flashcards
receptor-mediated signaling
- neurotranmitters bind to specific receptors on the postsynaptic neuron
- binding causses either the opening of ion channels or the activation of second messsenger system, altering the postsynaptic activity.
explain the transmitter-gated ion channels
- Neurotransmitters released by the presynaptic neuron bind to specific binding sites on the transmitter-gated ion-channel
- This causes a conformational change in the receptor protein, which opens a channel in the plasma membrane
- Ions (e.g., Na+ or K+) flow into or out of the postsynaptic neuron through the open channel
- Changes in ion concentrations affect the resting potential of the postsynaptic neuron, influencing its excitability and ultimately leading to changes in its firing rate
give examples of transmitter-gated ion channels
- Examples: nicotinic acetylcholine receptors (nAChRs) for fast synaptic transmission and muscle contraction, GABA receptors ( inhibitory synaptic transmission), AMPA receptors (excitatory synaptic transmission)
explain G-protein coupled receptors (metabotropic receptors)
- Neurotransmitter molecules bind to receptor proteins embedded in the postsynaptic membrane
- The receptor proteins activate small proteins, called G-proteins, which are free to move along the intracellular face of the postsynaptic membrane
- The activated G-proteins activate “effector” proteins
what is receptor tyrosine kinases
Cell surface receptors that play a key role in signal transduction pathways. They are involved in long-term plasticity, learning, and memory by triggering intracellular signaling cascades.
how does receptor tyrosine kinases trigger intracellular signaling cascades
- Neurotransmitter binding: Neurotransmitters bind to specific sites on the RTK, causing a conformational change
- Activation: This change activates the receptor’s tyrosine kinase activity
- Auto-phosphorylation: The receptor phosphorylates its own tyrosine residues, creating docking sites for signaling proteins
- Signaling cascades: Docking proteins bind and trigger downstream events, leading to changes in gene expression, protein synthesis, and synaptic strength
examples of RTKs in synaptic plasticity
- EphB receptors: Involved in Hebbian learning and long-term potentiation (LTP)
- NMDA receptors: Important for LTP and long-term depression (LTD)
- Trk receptors: Facilitate neurotrophin signaling and synaptic plasticity
inbalance in serotonin, dopamine or norepinephine signaling
depression
reduced dopamine signaling due to neuron loss
parkison disease
dysregulation of neurotransmitter systems
anxiety, addiction, schizophrenia
function astrocytes
- Glutamate uptake and clearance: Prevents excitotoxicity by removing excess neurotransmitter
- Neurotransmitter regulation: Release and removal of neurotransmitters to maintain synaptic balance
- Synaptic plasticity: Release of neurotrophic factors like BDNF to promote neuron survival and synaptic strength
- Energy supply: Provide lactate and other energy substrates to meet neuronal energy demands
astrocytes interaction with neurons
- Gap junctions: Facilitate direct communication between astrocytes and neurons through shared ions and signaling molecules
- Chemical signaling: Astrocytes release gliotransmitters like ATP and glutamate, modulating synaptic transmission and neuronal activity
Stores and releases neurotransmitters into the synaptic cleft
Pre-synaptic terminal
Contains receptors that bind neurotransmitters and initiate signaling cascades in the receiving neuron
Post-synaptic spine:
function of adhesion molecules
- Anchor pre- and post-synaptic spines together for strong synaptic connections
- Regulate neurotransmitter release and reception
o Maintain synaptic plasticity, learning, and memory - Facilitate efficient synaptic transmission and proper receptor localization
dysregulation of adhesion molecules is implicated in disorders like
alzheimer, autism spectrum disorder, and schizophrenia
explain a bit about glut3 transporters
Glucose is metabolized via glycolysis and aerobic oxidation. Neuronal glucose uptake relies on GLUT3 transporters
What are the stages of cellular respiration
- Glycolysis: Conversion of glucose into pyruvate in the cytosol, generating ATP and NADH
- Citric acid cycle (Krebs cycle): Pyruvate enters mitochondria, forming acetyl-CoA, which generates NADH, FADH₂, and CO₂
- Oxidative phosphorylation: ATP is synthesized as electrons pass through the electron transport chain, driving the proton gradient
mitochondrial dysfunction (neural disorders)
oNeurological disorders: Impaired function is linked to conditions like mitochondrial myopathies, Parkinson’s, and Alzheimer’s
Increased reactive oxygen species (ROS) production
Excess ROS can damage cellular components like DNA, proteins, and lipids, exacerbating oxidative stress and mitochondrial dysfunction
Impaired calcium homeostasis
Impaired calcium homeostasis: Mitochondria regulate intracellular calcium levels. Dysregulated calcium handling affects muscle contraction and relaxation, leading to weakness and fatigue
Disrupted cellular signaling pathways
Mitochondria influence pathways involved in metabolism, apoptosis, and gene expression. Dysfunction can lead to abnormal cellular behavior
Increased apoptosis
Impaired mitochondria can trigger programmed cell death, leading to tissue wasting and degeneration
Mitophagy
Damaged mitochondria are usually removed via mitophagy. Impairment in this process can worsen mitochondrial dysfunction
Epigenetic changes:
Dysfunction can cause DNA methylation and histone modifications, altering gene expression and contributing to disease
Mitochondrial dynamics:
Normal mitochondrial fusion and fission maintain function. Disruption results in dysfunctional mitochondria and reduced ATP production
Impaired mitochondrial membrane potential: Essential
Essential for ATP production and electron transport chain function. Impairment leads to decreased ATP and increased ROS
Mitochondrial-targeted therapies:
Coenzyme Q10 (CoQ10): An antioxidant that supports mitochondrial energy production, improves ATP synthesis, and reduces oxidative stress
Nicotinamide adenine dinucleotide (NAD+): A coenzyme that enhances energy metabolism and mitigates oxidative stress
Ubiquinol: A reduced form of CoQ10 that directly targets mitochondria to boost energy production
vitamin c
helps reduce oxidative stress and prevent mitochondrial damage
vitamin E
protects against lipd peroxidation and mitochondrial damage
alpha-lipoic acid
reduces oxidative stress and improves insulin sensetivity.
