Neurochemistry Flashcards
What is neurochemistry, and why is it important?
Key Findings:
• Definition:
• Neurochemistry refers to the study of chemicals in the nervous system, including neurotransmitters, neuromodulators, and other molecules that influence brain function.
• It examines how chemical interactions affect behavior, cognition, and neurological disorders.
• Key Components:
• Neurotransmitters (e.g., dopamine, serotonin, GABA, glutamate) → Mediate communication between neurons.
• Neuromodulators (e.g., neuropeptides, endorphins) → Regulate neural activity over longer periods.
• Receptors & Enzymes → Influence how signals are transmitted and broken down.
• Importance:
• Essential for brain function, from learning and memory to mood regulation.
• Imbalances in neurochemicals are linked to neurological and psychiatric disorders (e.g., depression, schizophrenia, Parkinson’s disease).
• Target for many drugs, including antidepressants, antipsychotics, and stimulants.
Key Takeaway:
• Neurochemistry is the study of brain chemicals that regulate neural communication, affecting cognition, behavior, and mental health. Understanding it is crucial for treating neurological and psychiatric disorders.
Do neurotransmitters have different production rates and receptor sensitivities?
Key Findings:
• Variability in Neurotransmitter Production:
• Different neurotransmitters are produced at different rates, depending on neuronal activity, genetic factors, and environmental influences.
• Dopamine and serotonin, for example, are regulated by enzymes like tyrosine hydroxylase (for dopamine) and tryptophan hydroxylase (for serotonin), which can vary in activity.
• Neurotransmitter levels are also influenced by reuptake, degradation (e.g., MAO enzyme for monoamines), and presynaptic autoregulation.
• Differences in Receptor Sensitivity:
• Receptors vary in density and responsiveness across different brain regions and individuals.
• Upregulation: If neurotransmitter levels are low, the brain may increase receptor sensitivity or number (e.g., increased dopamine receptors in response to chronic dopamine depletion).
• Downregulation: If neurotransmitter levels are high (e.g., excess serotonin due to SSRIs), the brain may reduce receptor sensitivity to maintain balance.
• Genetic variations influence receptor function, such as dopamine D2 receptor (DRD2) polymorphisms, which can affect reward processing and addiction risk.
Key Takeaway:
• Neurotransmitter production and receptor sensitivity vary across individuals and brain regions, influenced by genetics, neuronal activity, and environmental factors. The brain adapts dynamically by upregulating or downregulating receptor function to maintain balance.
Neurotransmitters
• Endogenous substance – Made within the body
• exists in presynaptic axon terminals
• Presynaptic cell has the right enzyme to make the substance
• Substance is released when APs reach the axon terminal
• Receptors recognize the release of the substance and exist on the
postsynaptic membrane
• Application of the substance experimentally produces changes in the post
synaptic cell
• Blocking the release, prevents presynaptic activity from impacting post
synaptic activity
Key Findings:
• Neurotransmitters are endogenous substances, meaning they are naturally produced within the body.
• They are stored in presynaptic axon terminals and synthesized by specific enzymes in the presynaptic cell.
• When an action potential (AP) reaches the axon terminal, the neurotransmitter is released into the synaptic cleft.
• Postsynaptic receptors recognize and bind to the neurotransmitter, triggering changes in the postsynaptic cell (e.g., excitatory or inhibitory effects).
• Experimental application of a neurotransmitter mimics its natural function, proving its role in neural signaling.
• If neurotransmitter release is blocked, presynaptic activity no longer influences the postsynaptic cell, disrupting communication.
Key Takeaway:
• Neurotransmitters are naturally produced chemicals that enable synaptic communication by binding to postsynaptic receptors. Blocking their release prevents signal transmission, confirming their essential role in neural activity.
What are the major types of neurotransmitters, and how do they function?
Key Findings:
• 1. Amine Neurotransmitters → Derived from modified amino acids, involved in mood, movement, and cognition.
• Examples:
• Dopamine (DA) – Reward, motivation, motor control.
• Serotonin (5-HT) – Mood regulation, sleep, appetite.
• Norepinephrine (NE) – Arousal, attention, stress response.
• Acetylcholine (ACh) – Learning, memory, muscle activation.
• 2. Amino Acid Neurotransmitters → Most abundant in the brain, responsible for fast excitatory or inhibitory signaling.
• Examples:
• Glutamate – Major excitatory neurotransmitter, essential for learning and plasticity.
• GABA (Gamma-aminobutyric acid) – Major inhibitory neurotransmitter, regulates anxiety and neuronal excitability.
• Glycine – Inhibitory neurotransmitter in the spinal cord and brainstem.
• 3. Peptide Neurotransmitters (Neuropeptides) → Short chains of amino acids, modulate longer-lasting brain functions.
• Examples:
• Endorphins & Enkephalins – Natural painkillers, mood regulation.
• Oxytocin & Vasopressin – Social bonding, stress response.
• Substance P – Pain transmission.
• 4. Gas Neurotransmitters → Unconventional, diffuse freely across membranes instead of binding to receptors.
• Examples:
• Nitric Oxide (NO) – Regulates blood flow, modulates synaptic plasticity.
• Carbon Monoxide (CO) – Involved in neural signaling, though less studied.
Key Takeaway:
• Neurotransmitters fall into four categories: amines (dopamine, serotonin), amino acids (glutamate, GABA), peptides (endorphins, oxytocin), and gases (nitric oxide). Each plays a critical role in brain function, from fast synaptic transmission to long-term modulation.
What are the brain’s primary excitatory and inhibitory neurotransmitters?
Main Excitatory Neurotransmitter:
• Glutamate → The primary excitatory neurotransmitter in the brain.
• Involved in learning, memory, and synaptic plasticity.
• Activates receptors like AMPA, NMDA, and Kainate, which help strengthen synaptic connections.
• Excessive glutamate activity can lead to excitotoxicity, contributing to neurodegenerative diseases (e.g., stroke, Alzheimer’s disease).
• Main Inhibitory Neurotransmitter:
• GABA (Gamma-Aminobutyric Acid) → The primary inhibitory neurotransmitter in the brain.
• Reduces neuronal excitability to prevent overactivation, maintaining balance in neural circuits.
• Activates GABA_A receptors (fast inhibition, ionotropic) and GABA_B receptors (slow inhibition, metabotropic).
• Low GABA levels are linked to anxiety, seizures, and hyperactivity.
Key Takeaway:
• Glutamate is the main excitatory neurotransmitter, essential for learning and synaptic plasticity, while GABA is the main inhibitory neurotransmitter, maintaining neural balance and preventing overexcitation.
What is acetylcholine, what does “cholinergic” mean, and what are its functions?
Key Findings:
• Acetylcholine (ACh):
• A key amine neurotransmitter involved in learning, memory, attention, and muscle activation.
• Plays a role in both the central nervous system (CNS) and peripheral nervous system (PNS).
• Cholinergic System (Cholinergic = Acetylcholine-Using Neurons):
• “Cholinergic” refers to neurons that produce and release acetylcholine.
• Key cholinergic pathways in the brain:
• Basal forebrain (nucleus basalis, medial septum) → Important for learning and memory.
• Pons and midbrain regions → Involved in arousal and REM sleep regulation.
• Neuromuscular junction → Acetylcholine is essential for muscle contractions in the somatic nervous system.
• Link to Alzheimer’s Disease:
• Alzheimer’s disease (AD) is associated with a severe loss of cholinergic neurons in the basal forebrain, leading to memory deficits.
• Reduced ACh levels impair synaptic plasticity and cognitive function.
• Acetylcholinesterase inhibitors (e.g., donepezil, rivastigmine) are used to increase ACh levels in AD patients to slow cognitive decline.
Key Takeaway:
• Acetylcholine is a critical neurotransmitter for memory, learning, and movement. Cholinergic neurons are essential for cognitive function, and their degeneration in the basal forebrain is linked to Alzheimer’s disease, contributing to memory loss.
What are monoamine neurotransmitters, and what functions do they serve?
Key Findings:
• Definition:
• Monoamine neurotransmitters are a class of neurotransmitters derived from a single amino acid.
• They play essential roles in mood regulation, arousal, motivation, and cognition.
• Types of Monoamine Neurotransmitters:
• Catecholamines (Derived from Tyrosine):
• Dopamine (DA) → Reward, motivation, motor control.
• Norepinephrine (NE) → Arousal, attention, stress response.
• Epinephrine (Adrenaline) → Fight-or-flight response.
• Indolamines (Derived from Tryptophan):
• Serotonin (5-HT) → Mood regulation, appetite, sleep, cognition.
• Melatonin → Sleep-wake cycle regulation.
• Monoamine System and Mental Health:
• Imbalances in monoamines are linked to psychiatric disorders:
• Low dopamine → Parkinson’s disease, anhedonia, motivation deficits.
• Low serotonin → Depression, anxiety disorders.
• Overactive dopamine → Schizophrenia (linked to hallucinations).
• Many psychiatric drugs target monoamine systems:
• SSRIs (Selective Serotonin Reuptake Inhibitors) → Increase serotonin to treat depression.
• Dopamine antagonists → Used in schizophrenia treatment.
Key Takeaway:
• Monoamine neurotransmitters, including dopamine, serotonin, and norepinephrine, regulate mood, motivation, and cognition. Their imbalance is associated with various psychiatric and neurological disorders.
Where is dopamine found in neurons, and what are the mesostriatal and mesolimbocortical dopamine pathways?
Key Findings:
• Dopamine Production and Location in Neurons:
• Dopamine-producing neurons are primarily found in the midbrain, specifically:
• Substantia nigra
• Ventral tegmental area (VTA)
• Dopamine Pathways:
• 1. Mesostriatal (Nigrostriatal) Pathway → Motor Control
• From: Substantia nigra (SN)
• To: Striatum (caudate nucleus & putamen)
• Function: Controls voluntary movement and motor coordination.
• Associated Disorder: Parkinson’s disease → Degeneration of this pathway leads to motor deficits (tremors, rigidity, bradykinesia).
• 2. Mesolimbocortical Pathway → Reward, Motivation, and Cognition
• From: Ventral tegmental area (VTA)
• To: Nucleus accumbens, amygdala, hippocampus, and prefrontal cortex
• Function: Motivation, reward processing, reinforcement learning, and cognition.
• Associated Disorders:
• Overactivity → Schizophrenia (linked to hallucinations and delusions).
• Dysfunction → Addiction (reinforcement of drug-seeking behavior).
Key Takeaway:
• The mesostriatal dopamine pathway regulates movement (degeneration causes Parkinson’s), while the mesolimbocortical pathway controls reward and motivation (dysfunction is linked to schizophrenia and addiction).
What is serotonin, where is it produced, and what functions does it serve in the brain and body?
Key Findings:
• What Is Serotonin (5-HT)?
• Serotonin is a monoamine neurotransmitter, derived from the amino acid tryptophan.
• It plays a broad modulatory role in the brain and body, affecting mood, sleep, appetite, arousal, pain, and cognition.
• Where Is It Produced?
• Primarily produced in the raphe nuclei of the brainstem, especially the dorsal raphe nucleus.
• Serotonergic neurons send widespread projections throughout the brain, including the cortex, limbic system, and spinal cord.
• Functions of Serotonin:
• Mood Regulation: Low levels linked to depression and anxiety.
• Sleep and Wakefulness: Regulates circadian rhythms and promotes sleep onset.
• Appetite: Involved in satiety signals (feeling full).
• Pain Processing: Modulates pain perception in the spinal cord.
• Cognition: Influences learning and memory.
• Clinical Relevance:
• Depression and Anxiety Disorders: Often linked to low serotonin activity.
• Selective Serotonin Reuptake Inhibitors (SSRIs):
• Common antidepressants (e.g., fluoxetine, sertraline) that increase serotonin availability at synapses by blocking reuptake.
• Also implicated in disorders like OCD, PTSD, and migraines.
Key Takeaway:
• Serotonin is a critical neurotransmitter produced in the raphe nuclei that influences mood, sleep, appetite, pain, and cognition. Its dysfunction is linked to mood disorders, and it is a primary target for antidepressant medications like SSRIs.
What are norepinephrine and noradrenaline, and what roles do they play in the brain?
Key Findings:
• What Are They?
• Norepinephrine (NE) and noradrenaline refer to the same neurotransmitter—the name “norepinephrine” is commonly used in the U.S., while “noradrenaline” is more common internationally.
• It is a monoamine neurotransmitter and hormone, derived from dopamine.
• Where Is It Produced?
• Produced primarily in the locus coeruleus, a small nucleus in the pons of the brainstem.
• Locus coeruleus neurons send widespread projections throughout the brain, including the cortex, hippocampus, cerebellum, and spinal cord.
• Functions of Norepinephrine:
• Arousal and alertness: Increases vigilance and attention.
• Stress response: Part of the sympathetic nervous system; increases heart rate and blood pressure.
• Mood regulation: Plays a role in depression and anxiety.
• Memory consolidation under emotionally arousing conditions.
• Noradrenergic System:
• Refers to neurons that release norepinephrine.
• These neurons regulate mood, attention, arousal, and fight-or-flight responses.
• Locus Coeruleus Code Rules:
• Low baseline activity: Promotes focused attention and selective task performance.
• High tonic activity: Associated with distractibility and stress.
• Phasic bursts: Support learning and adaptation to salient stimuli.
Key Takeaway:
• Norepinephrine (noradrenaline) is produced in the locus coeruleus and plays a vital role in arousal, attention, and stress responses. The noradrenergic system uses NE to modulate brain-wide activity, following locus coeruleus activation patterns that influence cognitive performance.
Why do many peptides act as neurotransmitters, and what are opioid peptides?
Key Findings:
• Why Peptides Act as Neurotransmitters:
• Peptides are short chains of amino acids that can act as neurotransmitters or neuromodulators.
• They are often co-released with classical neurotransmitters to modulate the intensity, duration, or sensitivity of synaptic signals.
• Peptides bind to metabotropic (G-protein coupled) receptors, leading to longer-lasting and broader effects than fast-acting neurotransmitters.
• They are involved in complex processes like pain, emotion, stress, reward, and homeostasis.
• Opioid Peptides:
• A family of peptide neurotransmitters that bind to opioid receptors in the brain and body.
• Main Types:
• Endorphins
• Enkephalins
• Dynorphins
• Functions:
• Pain relief (analgesia)
• Euphoria and reward
• Stress reduction
• Regulation of breathing, appetite, and mood
• Opioid peptides mimic the action of opiate drugs like morphine and heroin, but are produced naturally in the body.
Key Takeaway:
• Peptides act as neurotransmitters to modulate complex brain functions, often alongside traditional transmitters. Opioid peptides are natural pain-relievers and mood regulators that act on the same receptors as opiate drugs.
How do drugs interact with receptors, and what determines their effects?
Key Findings:
• Drugs can be designed to bind selectively (选择性结合) to specific receptor subtypes (受体亚型).
• Since receptor subtypes have different locations and functions, the same drug can have varying effects in different parts of the brain.
• Drug binding is usually temporary—once the drug is removed, the receptor returns to normal function.
Key Takeaway:
• Drugs exert effects by binding to specific receptors, but their impact depends on receptor subtype, location, and whether the binding is competitive or noncompetitive.
What is the difference between competitive and noncompetitive ligands in drug action?
Key Findings:
• Competitive Ligands (竞争性配体):
• Bind to the same receptor site (相同的受体部位) as the endogenous neurotransmitter (内源性神经递质).
• Can act as:
• Agonists (激动剂) → Activate the receptor (激活受体).
• Antagonists (拮抗剂) → Block receptor activation (阻止受体激活).
• Inverse Agonists (反向激动剂) → Produce the opposite effect of the neurotransmitter (产生相反作用).
• Noncompetitive Ligands (非竞争性配体):
• Bind to modulatory sites (调节位点) on the receptor, not the main active site.
• Can alter receptor function (改变受体功能) without directly competing with the neurotransmitter.
Key Takeaway:
• Competitive ligands directly compete with neurotransmitters for the receptor, while noncompetitive ligands bind elsewhere to modulate receptor activity.
What are the different ways drugs can affect receptor activity?
Key Findings:
• Ligand (配体): Any substance that binds to a receptor (结合受体的物质).
• Agonist (激动剂): Mimics (模拟) the neurotransmitter’s action, activating the receptor.
• Antagonist (拮抗剂): Blocks (阻断) receptor activation, preventing neurotransmitter effects.
• Inverse Agonist (反向激动剂): Produces the opposite effect (产生相反作用) of the normal neurotransmitter.
Key Takeaway:
• Drugs can enhance, block, or reverse receptor activity depending on whether they act as agonists, antagonists, or inverse agonists.
What is binding affinity, and why is it important in drug action?
Key Findings:
• Binding Affinity (结合亲和力):
• Refers to how strongly a drug or ligand binds to a receptor.
• A higher affinity means the drug binds tightly and stays attached longer, requiring a lower concentration to activate or block the receptor.
• A lower affinity means the drug binds weakly and detaches quickly, needing a higher concentration for effects.
• Importance in Drug Action:
• High-affinity drugs can be effective at lower doses, reducing side effects.
• Low-affinity drugs may require higher doses, increasing the risk of off-target effects.
• Example:
• Morphine has a high affinity for opioid receptors, making it a potent pain reliever at low doses.
• Aspirin has a lower affinity for its target enzymes, requiring higher doses for pain relief.
Key Takeaway:
• Binding affinity determines how strongly a drug interacts with its receptor, affecting potency, dosage, and therapeutic effectiveness.
What is drug efficacy, and how do partial agonists function?
Key Findings:
• Efficacy (药物效能):
• Refers to a drug’s ability to activate a receptor and produce a biological effect.
• High-efficacy drugs produce strong activation of the receptor.
• Low-efficacy drugs activate the receptor weakly, even if they have high binding affinity.
• Types of Agonists Based on Efficacy:
• Full Agonists (完全激动剂):
• Fully activate the receptor, producing maximum biological response (e.g., morphine at opioid receptors).
• Partial Agonists (部分激动剂):
• Bind to the receptor but produce only a partial response, even at full receptor occupancy.
• Can act as a weaker alternative to full agonists or as a competitive inhibitor by preventing full agonists from binding.
• Example: Buprenorphine (used in opioid addiction treatment) binds to opioid receptors but produces a weaker effect than full opioids like heroin, helping to reduce withdrawal symptoms.
Key Takeaway:
• Efficacy describes how well a drug activates a receptor, with full agonists producing strong effects and partial agonists generating weaker responses while potentially blocking stronger agonists.
What do bioavailability and biotransformation mean in drug action?
Key Findings:
• Bioavailability (生物利用度):
• Refers to the fraction of a drug that reaches the bloodstream and is available for action.
• Influenced by:
• Absorption rate (how well it enters circulation)
• Metabolism (how much is broken down before reaching target tissues)
• Route of administration (e.g., oral drugs have lower bioavailability due to liver metabolism, while IV drugs have 100% bioavailability).
• Biotransformation (生物转化):
• The process by which the body metabolizes a drug, usually in the liver.
• Converts drugs into active metabolites (which may prolong effects) or inactive forms for elimination.
• First-pass metabolism (首过代谢): A process where oral drugs are partially broken down in the liver before entering circulation, reducing bioavailability.
Key Takeaway:
• Bioavailability determines how much of a drug reaches the bloodstream, while biotransformation refers to how the body metabolizes drugs, affecting their duration and potency.
What are the different ways drugs can be taken, and how do they affect drug action?
Key Findings:
• 1. Oral (口服, ingestion)
• Drug is swallowed, absorbed through the digestive tract, and enters the bloodstream.
• Slower onset due to first-pass metabolism in the liver, which reduces bioavailability.
• Example: Most prescription medications (e.g., aspirin, antidepressants).
• 2. Inhalation (吸入, sniffing or smoking)
• Drug is absorbed directly into the lungs and enters the bloodstream rapidly.
• Fast onset (seconds to minutes) because lungs provide a large surface area for absorption.
• Example: Nicotine, cocaine, anesthetic gases.
• 3. Injection (注射, intravenous, intramuscular, subcutaneous)
• Intravenous (IV, 静脉注射) → Directly into the bloodstream, providing immediate effect.
• Intramuscular (IM, 肌肉注射) → Absorbed into muscle, slightly slower than IV.
• Subcutaneous (SC, 皮下注射) → Injected under the skin, absorbed gradually.
• Example: Morphine (IV), vaccines (IM), insulin (SC).
• 4. Transdermal (透皮吸收, via thin skin layers)
• Drug is absorbed through the skin, typically using patches.
• Slow but sustained release into the bloodstream.
• Example: Nicotine patches, hormone patches.
Key Takeaway:
• Drug administration routes affect how quickly and effectively a drug reaches the bloodstream. Oral is slower due to digestion, inhalation is rapid through the lungs, injection provides direct effects, and transdermal methods offer slow, controlled release.
What is drug tolerance, and how do metabolic and functional tolerance differ?
Key Findings:
• Drug Tolerance (耐受性):
• A decrease in drug effectiveness after repeated use, requiring higher doses to achieve the same effect.
• Can develop for both therapeutic drugs (e.g., painkillers) and addictive substances.
• Types of Drug Tolerance:
1. Metabolic Tolerance (代谢耐受性)
• The body becomes more efficient at breaking down the drug before it reaches its target.
• Often occurs in the liver, where enzymes become more active in metabolizing the drug.
• Example: Chronic alcohol use increases alcohol dehydrogenase activity, leading to faster breakdown and weaker effects.
2. Functional Tolerance (功能耐受性)
• The targeted receptors in the brain become less responsive to the drug.
• Upregulation (上调): If a drug blocks receptors, the body increases receptor numbers to compensate.
• Downregulation (下调): If a drug overstimulates receptors, the body reduces receptor numbers to prevent overstimulation.
• Example: Long-term opioid use downregulates opioid receptors, reducing pain relief effects.
Key Takeaway:
• Drug tolerance reduces drug effects over time. Metabolic tolerance occurs when the body breaks down the drug more efficiently, while functional tolerance happens when neural receptors adjust to prolonged drug exposure.
What is receptor regulation, and what does upregulation mean?
Key Findings:
• Receptor Regulation (受体调节):
• The process by which neurons adjust the number or sensitivity of receptors in response to changes in neurotransmitter levels or drug exposure.
• Helps maintain balance (homeostasis) in neural signaling.
• Upregulation (上调):
• Occurs when the body increases the number of receptors on the cell surface.
• Usually happens when neurotransmitter levels are low or when a drug blocks receptors.
• Example: If a person takes a drug that blocks dopamine receptors, the brain may produce more dopamine receptors to compensate.
• Downregulation (下调, opposite of upregulation):
• Occurs when the body decreases receptor numbers in response to excess neurotransmitters or drug stimulation.
• Example: Long-term opioid use downregulates opioid receptors, leading to drug tolerance and withdrawal symptoms when the drug is removed.
Key Takeaway:
• Receptor regulation allows the brain to adapt to changes in neurotransmitter levels. Upregulation increases receptor numbers when neurotransmitters are low, while downregulation decreases receptors when overstimulation occurs.
What are withdrawal symptoms and sensitization in drug use?
Key Findings:
• Withdrawal Symptoms (戒断症状):
• Negative physical and psychological effects that occur when drug use is suddenly stopped after prolonged use.
• Caused by the brain adapting to drug presence, leading to dysregulation when the drug is removed.
• Symptoms depend on the drug type:
• Opioids (e.g., heroin, morphine) → Pain, sweating, nausea, anxiety.
• Alcohol → Tremors, seizures, confusion (severe cases: delirium tremens).
• Nicotine → Irritability, cravings, sleep disturbances.
• Often linked to downregulation of receptors, meaning the body now needs the drug to function normally.
• Sensitization (敏化作用):
• The opposite of tolerance—instead of needing more drug for an effect, the user experiences stronger effects over time with repeated exposure.
• Can occur for some drug effects but not others (e.g., a stimulant may cause increasing hyperactivity but no increase in pleasure).
• Example:
• Cocaine sensitization → Repeated use may increase dopamine system activation, leading to heightened drug cravings and stronger behavioral effects even at the same dose.
• Amphetamines → Chronic exposure can cause exaggerated locomotor activity and paranoia.
Key Takeaway:
• Withdrawal symptoms occur when the brain struggles to function without a drug after prolonged use, while sensitization is when a drug produces stronger effects over time instead of weaker ones.
What is the AlphaFold Protein Structure Database, and why is it important
Key Findings:
• What Is AlphaFold?
• AlphaFold is an AI-powered protein structure prediction system, developed by DeepMind.
• It uses deep learning algorithms to accurately predict 3D structures of proteins from their amino acid sequences.
• The AlphaFold Protein Structure Database is a public repository containing millions of protein structures, including those from humans, bacteria, and other organisms.
• Why Is It Important?
• Faster and More Accurate Protein Modeling → Traditional X-ray crystallography and Cryo-EM take months to years, while AlphaFold can predict structures in hours to days.
• Accelerates Drug Discovery → Helps scientists understand protein functions, identify drug targets, and develop new treatments.
• Advances Biology and Medicine → Used in studying genetic diseases, vaccine development, and enzyme engineering.
• Example Applications:
• Identifying viral protein structures (e.g., COVID-19 research).
• Understanding neurodegenerative diseases (e.g., Alzheimer’s protein misfolding).
• Designing synthetic enzymes for industrial and medical use.
Key Takeaway:
• The AlphaFold Protein Structure Database provides AI-predicted 3D structures of proteins, revolutionizing biology by accelerating drug discovery, disease research, and protein engineering.
What is conduction aphasia, what are the main types of neurotransmitters, and what are their key functions and brain pathways?
Key Findings:
• Conduction Aphasia (传导性失语症)
• A type of acquired aphasia.
• Comprehension is intact, but the patient has specific difficulty repeating spoken words.
• Caused by damage to the arcuate fasciculus (弓状束), a white matter tract that connects Broca’s and Wernicke’s areas.
• Types of Neurotransmitters (神经递质类型)
1. Amines (胺类)
• Includes dopamine, norepinephrine, serotonin, acetylcholine.
2. Amino Acids (氨基酸类)
• Includes GABA (inhibitory), glutamate (excitatory).
3. Peptides (肽类)
• Includes endorphins, oxytocin, etc., with modulatory roles.
4. Gases (气体类)
• Includes nitric oxide (NO) – a retrograde messenger, diffuses freely.
• Neurotransmitters & Functions
• GABA: Main inhibitory NT, reduces neuronal excitability.
• Glutamate: Main excitatory NT, important for learning and plasticity.
• Dopamine: Involved in motivation, reward, and motor control.
• Mesocorticolimbic pathway (motivation/reward): VTA → Nucleus accumbens, cortex.
• Mesostriatal pathway (motor control): Substantia nigra → Striatum.
• Serotonin: Regulates mood, satisfaction, sleep, calming effect.
• Norepinephrine: Promotes arousal and alertness, also related to sleep-wake regulation.
• Nitric Oxide (NO): A retrograde neurotransmitter involved in plasticity and vasodilation.
• Relevant Brain Areas
• Substantia Nigra (黑质): Releases dopamine, crucial for motor function.
• Basal Ganglia (基底节): Involved in movement control and influenced by dopamine and glutamate.
Key Takeaway:
• Conduction aphasia results from arcuate fasciculus damage, impairing repetition but sparing comprehension. Neurotransmitters fall into 4 main types, each with distinct roles and pathways that regulate mood, movement, and cognition.
How do drugs influence synaptic transmission, and what mechanisms are involved?
Key Findings:
• Agonists (激动剂):
• Drugs that mimic neurotransmitters (NTs) by binding to the same receptors and activating them.
• Example: Morphine mimics endorphins.
• Antagonists (拮抗剂):
• Drugs that block neurotransmitter action, often by binding to the receptor without activating it.
• Prevent the natural NT from binding.
• Other Drug Actions at Synapses:
• Increase NT production (e.g., L-DOPA → increases dopamine).
• Block reuptake of NTs → increases NT in the synaptic cleft.
• Example: SSRIs block serotonin reuptake → more serotonin remains available.
• Modulators (调节剂): Drugs that enhance or reduce the effect of other neurotransmitters.
• Can increase or decrease the postsynaptic potential indirectly.
• Binding Types:
• Competitive binding (竞争性结合): Drug and NT compete for the same receptor site.
• Noncompetitive binding (非竞争性结合): Drug binds to a different site, altering receptor activity without blocking the NT directly.
Key Takeaway:
• Drugs can act as agonists, antagonists, reuptake blockers, or modulators, influencing neurotransmission by altering production, release, binding, or breakdown. Their effects depend on where and how they interact with the receptor system.
