Intro to Neuro Flashcards
Blood brain barrier (BBB) general
-talk about the different components of the BBB
- Capillaries = endothelial cells ONE layer thick surrounded by basement
membrane - Non-neural capillaries have small gaps (intercellular clefts) and fenestra for small molecules to pass
- Within the brain, capillaries have intercellular clefts which are closed by a network of astrocytes and pericytes, forming tight junctions. Fenestra are absent.
- Astrocytes surround about 85% of capillaries
Blood brain barrier - purpose, transporters and what can and cannot get through
- Reduces diffusion of ionized or hydrophilic molecules
- CNS drugs must be nonionized &/or lipid soluble
- Water-soluble materials are moved by specific transport processes (sugars,
amino acids) by facilitated diffusion with carrier proteins - P-glycoprotein transporters can exclude certain compounds from the brain
Areas of BBB with higher permeability? (3 specific areas)
- Area Postrema: adjacent to the chemoreceptor trigger zone (CTZ)
› Allows toxins in blood to stimulate vomiting
› Apomorphine induces vomiting - The median eminence of the hypothalamus:
› Hypothalamic releasing factors transported by pituitary gland - Pineal gland: releases hormones into blood
Pharmacological uses of the BBB
-drugs or drug classes and how they can be affected by the BBB)
- 2nd Generation Antihistamines (loratadine/Claritin)
› Blocks H1 receptors in periphery but does not cross BBB - Carbidopa – dopa decarboxylase inhibitor that does not cross BBB
› Prevents conversion of levodopa into dopamine in periphery - Naloxegol (Movantik)
› Pegylated derivative of naloxone, does not cross BBB & reverses constipation produced by systemic opiate agonists
Anatomy of the brain: Spinal cord
Spinal cord: transmits messages via afferent & efferent neurons from periphery to CNS
› Site of action of some muscle relaxants & opioids
Anatomy of the brain: Brain Stem and cerebellum/ it’s clinical syndromes (which is located within)
-Brain stem: medulla, pons, cerebellum & midbrain
› 12 cranial nerves originate here
› Mediate sensory & motor function associated with special senses (visual, auditory, taste, smell, respiration, heart rate, GI functions)
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-Cerebellum: coordinates motor movement via inputs from vestibular system & cortices (auditory, visual, sensory, motor)
› Clinical syndromes characterized by awkwardness of intentional movements
—— Ataxia: awkwardness of posture & gait, poor motor coordination, balance & speech. Eye movement problems (nystagmus). Sometimes are a side effect of antiepileptic drugs (phenytoin, phenobarbital, alcohol, benzodiazepines & lithium)
——–Asthenia: muscles tire more easily than normal
——- Tremor: usually “intention tremors” evident during purposeful movements
Anatomy of the brain: Reticular formation (RAS)
- Reticular formation (RAS): medulla to midbrain
› One neuron in RF may have input from 10,000 other neurons & makes contact with over 25,000 other neurons
› Regulates alertness/sleep, bp, heart rate & respiration
Anatomy of the brain: Thalamus
Relays motor & sensory signals to cerebral cortex
› Important in consciousness, sleep and sensory interpretation
Anatomy of the brain: midbrain
relay nuclei for auditory and visual systems
› DA neurons in substantia nigra (motor control); Parkinson’s disease
› DA neurons in ventral tegmental area (emotion/cognition); Schizophrenia
Anatomy of the brain
-Extrapyramidal motor system: Basal ganglia
Basal ganglia: consist of Caudate nucleus, Putamen (striatum), and Globus Pallidu
› Receives dopaminergic innervation from substantia nigra.
Disorders and diseases of the basal ganglia . . .
1.) Parkinsonism: rigidity, slowness, resting tremor, masked facies, shuffling gait
› assoc with degeneration of basal ganglia & substantia nigra
› Treat by increasing DA function in BG
2.) Chorea: brief/abrupt, irregular, non-repetitive, purposeless jerky involuntary movements affecting especially the shoulders, hips, and face (Sydenham’s chorea, Huntington’s Chorea)
› Treat with decreasing DA or enhancing GABA
3.) Athetosis: slow writhing/snake-like movements, esp. fingers & wrists
› Treat by decreasing DA
4.) Tardive Dyskinesia: characterized by repetitive, involuntary, purposeless movements caused by longterm antipsychotic treatment.
› Treat by decreasing DA
Anatomy of the brain: Hypothalamus
integrating region for ANS
- Regulates body temp, water balance, hunger & hormone levels in blood
Anatomy of the brain: Limbic system/ it’s components/ functions?
Limbic system: hippocampus, amygdala, septum, and projections into the prefrontal cortex, cingulate cortex, and enterorhinal cortex
— Responsible for complex emotions, motivation, short term memory
Anatomy of the brain: Cerebral cortex
Cerebral cortex: higher cognitive & emotional functions
- Information processing by modality: somatosensory, visual, auditory, olfactory, motor, association, sleep
Describe neuron synapses
Inside the axon terminal of a sending cell are many synaptic vesicles. These are membrane-bound spheres filled with neurotransmitter molecules. There is a small gap between the axon terminal of the presynaptic neuron and the membrane of the postsynaptic cell, and this gap is called the synaptic cleft.
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When an action potential, or nerve impulse, arrives at the axon terminal, it activates voltage-gated calcium channels in the cell membrane. Ca2+ which is present at a much higher concentration outside the neuron than inside, rushes into the cell. The Ca2+ allows synaptic vesicles to fuse with the axon terminal membrane, releasing neurotransmitter into the synaptic cleft.
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The molecules of neurotransmitter diffuse across the synaptic cleft and bind to receptor proteins on the postsynaptic cell. Activation of postsynaptic receptors leads to the opening or closing of ion channels in the cell membrane. This may be depolarizing—make the inside of the cell more positive—or hyperpolarizing—make the inside of the cell more negative—depending on the ions involved.
Cell membrane structure and its transporter/ how they behave
Process of when a neurotransmitter/ other messenger binds to receptor . . . what happens?
POSTSYNAPTIC RECEPTORS: Receptor number is dependent on the
concentration of agonist!!!
- Chronic excess of agonist = decrease in # of receptors
DOWNREGULATION: results in desensitization to the agonist
. - Chronic deficit of agonist (due to denervation, depletion of nt, or presence of an antagonist blocking receptors
UPREGULATION: results in supersensitivity to the agonist
Transporters: Uptake and reuptake
- Transporters are on presynaptic terminals (purple)
› Control the reuptake of nt back into the presynaptic terminal
› Transporter antagonists (blockers) bind directly to transporters and prevent reuptake - Causes a higher concentration of nt (or agonist) to evoke a response in postsynaptic neuron
Transporters: Derived from a genetic family of transporters. . . list the dif transporters
› NET : norepinephrine transporter
› SERT: serotonin (5-hydroxytryptamine; 5HT) transporter
› DAT: dopamine transporter
› GAT 1,2,3: GABA transporter
Characteristics of transporters:
- DAT & NET may transport both ways (amphetamine)
- Cocaine blocks all 3 monoamine transporters
- Tricyclic antidepressants (i.e. amitriptyline) only block SERT & NET
- SSRI’s (Selective Serotonin Reuptake Inhibitors) i.e. fluoxetine, paroxetine
- SNRI’s (Selective Norepinephrine Reuptake Inhibitors) i.e. venlafaxine, duloxetine
Define Neurotransmitter and Neuromodulator
- ) Neurotransmitter: a substance released from one neuron that induces activity in another neuron or tissue (ex: dopamine, serotonin, norepinephrine, GABA, Glu)
- ) Neuromodulator: substance released from one neuron that has little effect by itself but alters the response to other neurotransmitters (i.e benzodiazepines)
Neurotransmitter: Acetylcholine
- Acetylcholine: chief neurotransmitter of the parasympathetic nervous system (Rest portion) that
contracts smooth muscles, dilates blood vessels, increases bodily secretions, and slows heart rate.
- Synthesized by choline transferase stored in vesicles
- Degraded in synaptic cleft by Acetylcholinesterase to be recycle
Cholinergic receptors: two main types
1.) Nicotinic Receptors: bind Ach & nicotine
› Ligand gated Ion channel “inotropic”
› Receptor activation usually results in excitation
› 2 subtypes: N1 & N2 (N1 located on skeletal muscle @ NMJ (somatic nervous system))
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2.) Muscarinic receptors: bind Ach and muscarine
› G-protein coupled receptors “metabotropic”
› Effects depend on the subtype of receptor
› 5 subtypes: M1 - M5
—- M1: Gq (excitatory) found in CNS, salivary glands, gastric glands
—–M2: Gi (inhibitory) found in heart, smooth muscle of bladder
—–M3: Gq(excitatory) found in exocrine glands, eye, lungs, GI, bladder
