A CNS-resident cell phagocytoses pathogens after meningitis. Which cell type is primarily responsible?
A. Astrocyte
B. Microglia
C. Oligodendrocyte
D. Ependymal cell

B. Microglia

The main interface between brain parenchyma and the CSF compartment is formed by:
A. Astrocytes
B. Microglia
C. Ependymal cells
D. Oligodendrocytes

C. Ependymal cells

Structurally, neurotransmitters are divided into:
A. Small nitrogen molecules and neuropeptides
B. Small steroid molecules and purines
C. Amino acids and lipids
D. Ions and peptides

A. Small nitrogen molecules and neuropeptides

Small nitrogen-containing neurotransmitters are generally synthesized in the:
A. Postsynaptic density
B. Nucleus
C. Myelin sheath
D. Presynaptic terminal

D. Presynaptic terminal

Small nitrogen-containing neurotransmitters are synthesized mainly from:
A. Fatty acids and cholesterol
B. Amino acids and glycolysis intermediates
C. DNA bases and ribose
D. Heme and bilirubin

B. Amino acids and glycolysis intermediates

Serotonin is synthesized from:
A. Tryptophan
B. Tyrosine
C. Serine
D. Glutamine

A. Tryptophan

Glutamate (and its derivative GABA) is derived from the TCA intermediate:
A. Oxaloacetate
B. Citrate
C. Alpha-ketoglutarate
D. Succinate

C. Alpha-ketoglutarate

In the brain, glycine is synthesized from:
A. Alanine
B. Glycine cleavage products
C. Tryptophan
D. Serine

D. Serine

After global cerebral ischemia, which process most directly amplifies neuronal injury in many regions?
A. Reduced synaptic vesicle fusion
B. Glutamate excitotoxicity
C. Decreased nitric oxide formation
D. Lower intracellular calcium

B. Glutamate excitotoxicity

A neurodegenerative disorder is linked to oxidative damage. Which pair is emphasized in pathogenesis?
A. Lactate and ketones
B. Chloride and bicarbonate
C. Free radicals and nitric oxide
D. Phosphate and sulfate

C. Free radicals and nitric oxide

During CNS development, which glial cell guides neuronal migration and helps form a stabilizing matrix?
A. Astrocyte
B. Microglia
C. Schwann cell
D. Oligodendrocyte

A. Astrocyte

A cell population lines the ventricles and can be specialized to secrete CSF. Which cells are these?
A. Microglia
B. Oligodendrocytes
C. Astrocytes
D. Ependymal cells

D. Ependymal cells

Impaired ventricular ciliary beating would most directly disrupt:
A. Neuronal action potentials
B. CSF circulation efficiency
C. Myelin compaction
D. Synaptic cleft reuptake

B. CSF circulation efficiency

Glucose crosses brain capillary endothelium primarily via facilitated diffusion through:
A. GLUT3
B. GLUT4
C. GLUT1
D. SGLT1

C. GLUT1

Neurons take up glucose from extracellular fluid primarily via:
A. GLUT3
B. GLUT2
C. GLUT5
D. GLUT4

A. GLUT3

An infant has seizures and a low CSF glucose despite normal serum glucose. This CSF finding is called:
A. Hyperglycorrhachia
B. Hyperglycemia
C. Glycosuria
D. Hypoglycorrhachia

D. Hypoglycorrhachia

Large neutral amino acids enter CSF rapidly via:
A. Multiple peptide transporters
B. A single amino-acid transporter
C. Passive diffusion only
D. Vesicular transcytosis

B. A single amino-acid transporter

High levels of one LNAA can reduce transport of others across the BBB via:
A. Competitive inhibition
B. Noncompetitive inhibition
C. Allosteric activation
D. Irreversible blockade

A. Competitive inhibition

Untreated PKU causes cognitive impairment; one proposed mechanism is reduced BBB entry of other amino acids due to excess:
A. Phenylalanine
B. Glycine
C. Tryptophan
D. Histamine

A. Phenylalanine

In maple syrup urine disease, impaired CNS amino-acid balance is most linked to excess blood:
A. Aromatic amino acids
B. Branched-chain amino acids
C. Sulfur amino acids
D. Acidic amino acids

B. Branched-chain amino acids

A patient started on reserpine later reports severe anhedonia and suicidal thoughts. The drug’s relevant primary action is:
A. Blocks dopamine receptors
B. Stimulates serotonin reuptake
C. Inhibits MAO activity
D. Blocks catecholamine vesicular uptake

D. Blocks catecholamine vesicular uptake

Which adverse psychiatric outcome was historically observed in a subset of patients taking reserpine?
A. Depression and suicidality
B. Mania and insomnia
C. Hallucinations and delusions
D. Euphoria and agitation

A. Depression and suicidality

The first and rate-limiting step in catecholamine synthesis from tyrosine is catalyzed by:
A. Dopamine beta-hydroxylase
B. COMT
C. Tyrosine hydroxylase
D. MAO

C. Tyrosine hydroxylase

Tyrosine hydroxylase requires which cofactor for activity?
A. NADPH oxidase
B. Tetrahydrobiopterin
C. Thiamine pyrophosphate
D. Biotin

B. Tetrahydrobiopterin

The immediate product of tyrosine hydroxylase is:
A. L-DOPA
B. Dopamine
C. Norepinephrine
D. Epinephrine

A. L-DOPA

The conversion of L-DOPA to dopamine requires which cofactor?
A. FAD
B. Biotin
C. THF
D. Pyridoxal phosphate

D. Pyridoxal phosphate

Epinephrine synthesis depends on adequate vitamin support to generate SAM, specifically:
A. Vitamin C and vitamin K
B. Vitamin B12 and folate
C. Thiamine and riboflavin
D. Niacin and biotin

B. Vitamin B12 and folate

Conversion of tyrosine to L-DOPA and L-DOPA to dopamine occurs in the:
A. Synaptic vesicle lumen
B. Mitochondrial matrix
C. Cytosol
D. Lysosome

C. Cytosol

Reserpine was historically used clinically primarily as a(n):
A. Antipsychotic and anxiolytic
B. Antiparkinson and antiemetic
C. Analgesic and antipyretic
D. Antihypertensive and antiepileptic

D. Antihypertensive and antiepileptic

Which set lists only major small nitrogen-containing neurotransmitters from the provided material?
A. Glutamate, GABA, glycine, histamine
B. Glutamate, histamine, oxytocin, GABA
C. Glycine, endorphin, dopamine, histamine
D. Acetylcholine, serotonin, insulin, GABA

A. Glutamate, GABA, glycine, histamine

A vesicular monoamine transporter shares homology with bacterial drug-resistance transporters. Which example fits this family?
A. P-glycoprotein
B. GLUT1
C. Dopamine transporter
D. Na+/K+ ATPase

A. P-glycoprotein

Vesicle transporters for monoamines typically span the membrane with how many transmembrane domains?
A. 4
B. 7
C. 12
D. 24

C. 12

Catecholamines are concentrated inside storage vesicles by a mechanism best described as:
A. Primary active transport
B. Secondary active transport
C. Simple diffusion
D. Channel-mediated influx

B. Secondary active transport

The catecholamine vesicular uptake process is ultimately driven by a:
A. Proton pump gradient
B. Sodium gradient
C. Chloride gradient
D. Calcium gradient

A. Proton pump gradient

In storage vesicles, catecholamines most characteristically exist complexed with:
A. Albumin and calcium
B. ATP and chromogranins
C. GTP and tubulin
D. Heme and ferritin

B. ATP and chromogranins

When chromogranins are released, they can be proteolytically processed into:
A. Inactive waste products
B. Neurotoxic aldehydes
C. Bioactive peptides
D. Membrane phospholipids

C. Bioactive peptides

A patient has episodic headaches, sweating, palpitations, and severe hypertension (pheochromocytoma). Which circulating marker may be elevated in this tumor type?
A. Chromogranins
B. C-reactive protein
C. Troponin I
D. Myoglobin

A. Chromogranins

Two major enzyme systems mediating catecholamine inactivation include:
A. AChE and GABA-T
B. COMT and MAO
C. CYP3A4 and UGT1A1
D. Renin and ACE

B. COMT and MAO

MAO is located primarily on the:
A. Inner mitochondrial membrane
B. Outer mitochondrial membrane
C. Nuclear envelope
D. Rough ER lumen

B. Outer mitochondrial membrane

MAO catalysis oxidizes the amino-bearing carbon to an aldehyde and releases:
A. Sulfate ion
B. Bicarbonate
C. Ammonium ion
D. Chloride ion

C. Ammonium ion

A drug selectively inhibiting MAO-A would most directly reduce deamination of:
A. Dopamine and histamine
B. Norepinephrine and serotonin
C. Acetylcholine and GABA
D. Glutamate and glycine

B. Norepinephrine and serotonin

MAO-B has relatively broader activity against:
A. Phenylethylamines
B. Purines
C. Peptides
D. Steroids

A. Phenylethylamines

A child with hypopigmentation is suspected to have albinism due to impaired tyrosine-to-melanin conversion. A potentially defective enzyme is:
A. Tryptophan hydroxylase
B. Copper-dependent tyrosine hydroxylase
C. Lactate dehydrogenase
D. Dopamine beta-hydroxylase

B. Copper-dependent tyrosine hydroxylase

COMT inactivates catecholamines by transferring a methyl group from:
A. NADPH
B. FAD
C. SAM
D. CoA

C. SAM

CSF homovanillylmandelic acid (HVA) is an indicator of:
A. Dopamine degradation
B. Serotonin synthesis
C. GABA recycling
D. Histamine storage

A. Dopamine degradation

Reduced CSF HVA would be most consistent with neuronal changes seen in:
A. Huntington disease
B. Alzheimer disease
C. ALS
D. Parkinson disease

D. Parkinson disease

A patient develops headaches, palpitations, nausea, vomiting, and high blood pressure after ingesting large amounts of aged foods. The culprit amine is:
A. Histamine
B. Serotonin
C. Tyramine
D. GABA

C. Tyramine

Tyramine is normally detoxified primarily by:
A. COMT
B. MAO-A
C. MAO-B
D. Acetylcholinesterase

B. MAO-A

A patient on an MAO inhibitor eats aged cheese and develops a hypertensive crisis. The key immediate mechanism is:
A. Tyramine releases norepinephrine
B. COMT blocks dopamine synthesis
C. VMAT blocks vesicle loading
D. MAO generates excess ammonium

A. Tyramine releases norepinephrine

Free cytosolic catecholamines downregulate tyrosine hydroxylase by competing for the enzyme’s:
A. Pyridoxal phosphate site
B. Heme binding pocket
C. Pterin cofactor binding
D. Acetyl-CoA docking site

C. Pterin cofactor binding

Which acute event in a nerve terminal activates tyrosine hydroxylase?
A. Hyperpolarization
B. Depolarization
C. Myelin loss
D. Axonal transport block

B. Depolarization

With prolonged sympathetic firing, increased transcription of tyrosine hydroxylase and dopamine β-hydroxylase occurs mainly in neuronal:
A. Synaptic clefts
B. Axon terminals
C. Nodes of Ranvier
D. Neuronal Perikarya

D. Neuronal Perikarya

The synthesis pathway of serotonin from tryptophan is most similar in logic to norepinephrine synthesis from tyrosine because both begin with:
A. Oxidation then phosphorylation
B. Hydroxylation then decarboxylation
C. Transamination then reduction
D. Glycosylation then cleavage

B. Hydroxylation then decarboxylation

In addition to catecholamines, serotonin is inactivated by:

A. COMT
B. AChE
C. MAO
D. DBH

C. MAO

The activity of several antipsychotic drugs is described here as being based on inhibiting:
A. MAO
B. COMT
C. VMAT
D. GLUT3

A. MAO

Melatonin is synthesized from the amino acid precursor:
A. Tyrosine
B. Serine
C. Tryptophan
D. Glycine

C. Tryptophan

A patient develops thrombocytopenia and thrombosis after heparin exposure due to antiheparin antibodies. This antibody-driven platelet activation is associated with release of:
A. Dopamine
B. Serotonin
C. Histamine
D. GABA

B. Serotonin

Within the brain, histamine is produced by:
A. Astrocytes and oligodendrocytes
B. Microglia and ependyma
C. Mast cells and neuronal fibers
D. Endothelium and pericytes

C. Mast cells and neuronal fibers

Histaminergic neuronal cell bodies in humans are concentrated in the:
A. Locus coeruleus
B. Dorsal raphe nucleus
C. Tuberomammillary nucleus
D. Substantia nigra

C. Tuberomammillary nucleus

The tuberomammillary nucleus lies within the:
A. Posterior basal hypothalamus
B. Anterior hypothalamus
C. Dorsal midbrain
D. Ventral medulla

A. Posterior basal hypothalamus

Histamine synthesis from histidine is catalyzed by:
A. Histamine N-methyltransferase
B. Tyrosine hydroxylase
C. DOPA decarboxylase
D. Histidine decarboxylase

D. Histidine decarboxylase

Histidine decarboxylase requires which cofactor?
A. Tetrahydrobiopterin
B. Pyridoxal phosphate
C. Biotin
D. FAD

B. Pyridoxal phosphate

The catalytic mechanism of histidine decarboxylase most resembles:
A. Tryptophan hydroxylase
B. Tyrosine hydroxylase
C. DOPA decarboxylase
D. Dopamine β-hydroxylase

C. DOPA decarboxylase

A serotonergic anorexigen decreases appetite via receptors on:
A. POMC neurons
B. Orexin neurons
C. GnRH neurons
D. CRH neurons

A. POMC neurons

The POMC neurons mediating Redux hypophagia are in the:
A. Paraventricular nucleus
B. Arcuate nucleus
C. Suprachiasmatic nucleus
D. Ventromedial nucleus

B. Arcuate nucleus

A drug that raises synaptic serotonin most directly promotes:
A. Hunger signaling
B. Anhedonia symptoms
C. Panic symptoms
D. Satiety signaling

D. Satiety signaling

Chronically low serotonin is associated with:
A. Increased appetite
B. Fixed satiety
C. Reduced appetite
D. Decreased thirst

A. Increased appetite

Redux raised synaptic serotonin by SSRI action plus:
A. Reduced vesicle fusion
B. Increased MAO activity
C. Increased serotonin secretion
D. Increased COMT activity

C. Increased serotonin secretion

After neuronal release, histamine is thought to activate:
A. Postsynaptic only
B. Pre and postsynaptic
C. Glial only
D. Extrasynaptic only

B. Pre and postsynaptic

Relative to many transmitters, histamine shows little:
A. Presynaptic recycling
B. Calcium-triggered release
C. Vesicular storage
D. Enzymatic synthesis

A. Presynaptic recycling

Major CNS uptake/inactivation of histamine is attributed to:
A. Microglia
B. Oligodendrocytes
C. Neurons
D. Astrocytes

D. Astrocytes

A first-generation antihistamine most commonly causes:
A. Euphoria
B. Tremor
C. Drowsiness
D. Mydriasis

C. Drowsiness

“Nondrowsy” antihistamines minimize sedation mainly due to:
A. Poor BBB penetration
B. Higher H2 selectivity
C. Rapid CSF clearance
D. Increased histamine release

A. Poor BBB penetration

Peripheral antihistamine effects primarily counter histamine-driven:
A. Platelet aggregation
B. Vasodilation permeability
C. Cardiac contractility
D. Insulin secretion

B. Vasodilation permeability

A proposed contributor to neurologic findings in B12 deficiency is impaired:
A. Choline synthesis
B. GABA synthesis
C. Melatonin synthesis
D. Dopamine synthesis

D. Dopamine synthesis

The key reaction supplying acetyl-CoA for acetylcholine synthesis is:
A. Citrate lyase
B. Ketone cleavage
C. Pyruvate dehydrogenase
D. Fatty acid synthase

C. Pyruvate dehydrogenase

Pyruvate dehydrogenase is located in the:
A. Mitochondria
B. Cytosol
C. Nucleus
D. ER lumen

A. Mitochondria

Lecithin (phosphatidylcholine) supplementation has been used for:
A. Myasthenia gravis
B. Parkinson disease
C. Alzheimer dementia
D. Tardive dyskinesia

D. Tardive dyskinesia

The highest physiologic demand for choline is in the:
A. Elderly adult
B. Neonate
C. Adolescent
D. Middle-aged adult

B. Neonate

Glutamate dehydrogenase forms glutamate by incorporating:
A. Carbon dioxide
B. Sulfate
C. Ammonia
D. Glucose

C. Ammonia

An alternative major route to glutamate from α-ketoglutarate uses:
A. Transamination
B. Phosphorylation
C. Glycosylation
D. Beta-oxidation

A. Transamination

The CNS recycling pathway conserving glutamate and GABA is the:
A. Cori cycle
B. Urea cycle
C. Malate-aspartate
D. GABA shunt

D. GABA shunt

A patient with epilepsy is given a drug that blocks GABA reuptake:
A. Vigabatrin
B. Gabapentin
C. Tiagabine
D. Diazepam

C. Tiagabine

Which amino acid cannot cross the BBB?
A. Alanine
B. Aspartate
C. Serine
D. Glycine

B. Aspartate

Nitric oxide (NO) is synthesized from which amino acid substrate?
A. Histidine
B. Arginine
C. Tyrosine
D. Serine

B. Arginine

A patient’s ABG shows PaO2 = 18 mm Hg during acute hypoxia. Most likely clinical state?
A. Somnolence
B. Confusion
C. Seizures
D. Coma

D. Coma

A shared metabolic consequence of all forms of hypoxia is:
A. Decreased neurotransmitter synthesis
B. Increased myelin synthesis
C. Increased CSF glucose
D. Enhanced synaptic recycling

A. Decreased neurotransmitter synthesis

Which enzyme represents a major anaplerotic reaction for the TCA cycle?
A. Pyruvate dehydrogenase
B. Citrate synthase
C. Pyruvate carboxylase
D. Malate dehydrogenase

C. Pyruvate carboxylase

Valine and isoleucine degradation replenishes the TCA cycle by producing:
A. Succinyl-CoA
B. Acetyl-CoA
C. Citrate
D. Oxaloacetate

A. Succinyl-CoA

A peroxisome biogenesis disorder (e.g., Refsum) injures brain cells largely due to failed metabolism of:
A. Ketones and lactate
B. Glucose and glycogen
C. Cholesterol and bile acids
D. VLCFAs and branched-chain AAs

D. VLCFAs and branched-chain AAs

Which lipid class is ~16% of myelin lipid and largely absent from other membranes?
A. Phosphatidylcholine
B. Cerebrosides
C. Triacylglycerols
D. Gangliosides

B. Cerebrosides

Galactosylcerebroside is best described as having:
A. Two sugars on glycerol
B. Phosphate headgroup on ceramide
C. Single sugar on sphingosine OH
D. Sulfate on cholesterol ring

C. Single sugar on sphingosine OH

Myelin lamellae are stabilized primarily by:
A. Protein–lipid and protein–protein
B. Disulfide bridges only
C. Ionic bonds only
D. Hydrogen bonds only

A. Protein–lipid and protein–protein

Two proteins comprising ~60–80% of CNS myelin protein are:
A. MAG protein and PMP22
B. P0 protein and PMP22
C. Myelin P2 and P0
D. Proteolipid protein and Myelin basic proteins

D. Proteolipid protein and Myelin basic proteins

What may help to stabilize the structure from within the membrane?

A. Proteolipid protein
B. P0 protein
C. Myelin basic protein
D. Myelin-associated glycoprotein

C. Myelin basic protein

Pre-op management to mask catecholamine-excess signs in pheochromocytoma most classically uses:
A. Propranolol then phenoxybenzamine
B. Phenoxybenzamine then propranolol
C. Propranolol only
D. Phenoxybenzamine only

B. Phenoxybenzamine then propranolol

Multiple sclerosis incidence is described as:
A. Near nil at Equator
B. Highest near Equator
C. Uniform worldwide distribution
D. Only tropical latitudes

A. Near nil at Equator

Modern MS treatment is now based mainly on blocking the:
A. Adrenergic system blockade
B. Glutamatergic system blockade
C. Immune system blockade
D. Cholinergic system blockade

C. Immune system blockade

Inherited mutations in P0 (major PNS myelin protein) most directly cause:
A. Multiple sclerosis
B. ALS
C. Guillain-Barré syndrome
D. Charcot-Marie-Tooth disease

D. Charcot-Marie-Tooth disease

The inheritance pattern classically described for Charcot-Marie-Tooth is:
A. Autosomal recessive
B. Autosomal dominant
C. X-linked recessive
D. Mitochondrial inheritance

B. Autosomal dominant

A PLP mutation in CNS myelin is associated with which leukodystrophy?
A. Krabbe disease
B. Metachromatic leukodystrophy
C. Pelizaeus-Merzbacher disease
D. Adrenoleukodystrophy

C. Pelizaeus-Merzbacher disease

The enzyme catalyzing NO formation from arginine is:
A. Nitric oxide synthase
B. Tyrosine hydroxylase
C. Histidine decarboxylase
D. DOPA decarboxylase

A. Nitric oxide synthase

Which branched-chain amino acids contribute succinyl-CoA via degradation?
A. Leucine and lysine
B. Valine and isoleucine
C. Phenylalanine and tyrosine
D. Tryptophan and serine

B. Valine and isoleucine

Mutations in the major CNS myelin protein can cause Pelizaeus-Merzbacher and X-linked spastic paraplegia type 2. The protein is:
A. P0 protein
B. Myelin basic protein
C. Myelin-associated glycoprotein
D. Proteolipid protein

D. Proteolipid protein