Toxic Responses of the Nervous System Flashcards
Three basic functions of the nervous system
Relays information, motor functions, Integrates thought processes, learning and memory
two fundamental anatomical divisions of the nervous system
central and peripheral nervous system
It is the control center, composed of brain and spinal cord
Central nervous system
T/F: the central nervous system analyzes information received from sensory receptors, and in response, it issues motor commands to control body functions
True
What are the two types of nerves under the peripheral nervous system?
Afferent nerves and efferent nerves
Modified T/F: Efferent nerves relays sensory information to the CNS. Afferent nerves relays motor commands from the CNS to the various muscles and glands
BOTH FALSE. Afferent nerves relays sensory information to the CNS. Efferent nerves relays motor commands from the CNS to the various muscles and glands
Efferent nerves are further organized into two systems, which are:
Somatic nervous system and Autonomic nervous system
Modified T/F: Somatic nervous system carries motor information to smooth muscles, cardiac muscles, and various glands. Autonomic nervous system is also known as the voluntary system, which carries motor information to the skeletal muscles.
BOTH FALSE. Autonomic nervous system carries motor information to smooth muscles, cardiac muscles, and various glands. Somatic nervous system is also known as the voluntary system, which carries motor information to the skeletal muscles.
T/F: Skeletal muscles, smooth muscles, cardiac muscles, and glands are effectors
True
What is the major difference between the somatic and autonomic nervous system?
conscious control
The nervous system is protected from the adverse effects of many potential toxicants by an anatomical barrier between the blood and the brain, or a ____________________
blood-brain barrier (BBB).
To gain entry to the nervous system, molecules must pass into the __________________ of endothelial cells of the brain rather than ________________ endothelial cells, as they do in other tissues.
cell membranes; between
among the unique properties of the endothelial cells in the nervous system is the presence of __________________ between the cells, this is why molecules cannot easily penetrate between them
tight junctures
T/F: the BBB contains xenobiotic transporters, which transports xenobiotics that have diffused through the endothelial cells back into the blood
True
If not actively transported into the brain, the penetration of toxicants or their metabolites is largely related to their _______________.
lipid solubility
The _______________, ______________, and a small number of other sites within the brain are not protected by blood-tissue barriers.
Spinal ganglia; autonomic ganglia
Neurons are highly dependent on ________________ because they use the energy to maintain proper ion gradients
aerobic metabolism
These lead to early signs of neuronal dysfunction
Cyanide and CO poisoning
neuronal dysfunction can be a combination of direct toxic effects on neurons and secondary damage from ________________________
systemic hypoxia or ischemia
It is a toxicant-induced irreversible loss of neurons, including its cytoplasmic extensions, dendrites, axons, and the myelin ensheathing the axon.
neuronopathy
This is where the axon degenerates while neuronal cell body continues to survive.
axonopathy
Modified T/F: Neuronopathy is characterized by loss of cell body and all of its processes with no potential for regeneration. Axonopathy includes loss of myelin surrounding the axon
BOTH TRUE
This is a functional assessment where sensory-specific information on nerve conduction velocity and integrity is assessed.
electrophysiological tests
This is an observation with regards to behavior. This is under functional assessments
Functional observational studies
Other types of functional observational studies
Irwin screens, tests of motor activity, and expanded clinical observations
Individual neurotoxic compounds typically target the _______, the _______, the myelinating cell, or the ___________________ system.
neuron; axon; neurotransmitter
Modified T/F: A large number of compounds are known to result in toxic neuronopathies. All of these toxicants share certain features.
BOTH TRUE
T/F:
Neuropathy pathway: apoptosis or necrosis –> initial injury to neurons –> permanent loss of neurons
False. Initial injury to neurons –> apoptosis or necrosis –> permanent loss of neurons
The neurotoxic effect of this neurotoxicant is the degeneration of the dorsal root ganglion cells, and axonal degeneration in the PNS
doxorubicin
The neurologic finding in this neurotoxicant includes ataxia, constriction of visual fields, paresthesias in adults, and psychomotor retardation (fetal exposure)
methylmercury (organic mercury)
The neurologic findings of this neurotoxicant includes tremors, and hyperexcitability in experimental animals
trimethyltin
T/F: doxorubicin, which is an antimitotic in cancer chemotherapy, exerts its effects on the neurons in the PNS, particularly, the dorsal root and autonomic ganglia by intercalating with the DNA and interfering with the transcription
True
This neurotoxicant targets neurons of the visual cortex; massive degeneration can lead to blindness and marked ataxia for adults
Methylmercury (organic mercury)
This neurotoxicant targets irreversible limbic-cerebellar syndrome in humans and similar behavioral changes in primates
trimethyltin
The children affected will usually have developmental deficits, retardation and even cognitive deficits
methylmercury (organic mercury)
this neurotoxicant may be found in plasticizers, antifungal agents, or pesticides
trimethyltin
The accumulation of methylmercury in the body from eating fish from bodies of water connected to chemical factories may lead to ________________
Minamata disease
The cellular basis of neurotoxicity of this neurotoxicant includes loss of hippocampal neurons, and on amygdala pyriform cortex
Trimethyltin
The cellular basis of neurotoxicity of methylmercury (organic mercury)
Neuronal degeneration in visual cortex, cerebellum, and ganglia. Spongy disruption in the cortex and cerebellum
These are chemicals associated with neuronal injury (neuropathies)
doxorubicin, methylmercury (organic mercury), and trimethyltin
primary site of axonopathies
axons
These are chemicals associated with axonal injury (axonopathies)
acrylamide, carbon disulfide, n-hexane, B,B’-Iminodipropionitrile, and organophosphorous compounds (NTE inhibitors)
Neurotoxicant: Acrylamide
Neurologic findings: peripheral neuropathy, which is often _________
Basis: axonal degeneration where the axon terminal is affected in its _________ stages
sensory
earliest
Neurotoxicant: Carbon disulfide
Neurologic findings: Acute ____________ and chronic _____________
Basis: axonal degeneration, early stages include _______________________
psychosis; peripheral neuropathy
neurofilamentous swelling
Neurotoxicant: n-Hexane
Neurologic finding: peripheral neuropathy, severe cases have ________
Basis: axonal degeneration, early neurofilamentous swelling (_________ and _________)
spasticity
PNS and spinal cord
Neurotoxicant: B,B’-Iminodipropionitrile
Neurologic finding: No data in humans; ___________________ in rats
Basis: ___________ axonal swellings, degeneration of _____________ epithelial cells and _________________ cells
excitatory movement
proximal; olfactory; vestibular hair
Neurotoxicant: Organophosphate compounds (NTE inhibitors)
Neurologic findings: acute _____________ and peripheral neuropathy
Basis: Axonal degeneration
abdominal pain
identify the neurotoxicant
These are classified as gamma-diketones
n-hexane and 2-hexanone
identify the neurotoxicant
distal axonopathy; covalent cross-linking of neurofilaments which can also lead to aberrations in mood and signs of diffuse encephalopathic disease
Carbon disulfide (CS2)
This syndrome is specifically for rats as there is not much record of its effect on humans. It exhibits excitement, circling, head twitching, or over-alertness which indicates that there is already degeneration of vestibular hair cells
Waltzing syndrome
Identify the neurotoxicant
Causes Waltzing syndrome
B,B’-Iminodipropionitrile (IDPN)
identify the neurotoxicant
distal axonopathy characterized by multiple axonal swellings
Acrylamide
T/F: the critical difference between central nervous system and peripheral nervous system axonal degeneration, is that in PNS, it can regenerate but for central axons, they cannot regenerate
True
Factors why central axons cannot regenerate
inhibitory factors that are secreted by oligodendrocytes, and astrocyte scarring, and glial interference
Modified T/F: Myelin provides electrical insulation of neuronal processes. In its absence, there is slowing of conduction and aberrant conduction of impulses between adjacent processes
BOTH TRUE
This myelinopathy is caused by alterations in transcript levels of myelin basic protein mRNA, where there is separation of myelin lamellae
Intramyelinic edema
This myelinopathy may result from progressive intramyelinic edema or from direct toxicity to myelinating cell, where there is selective loss of myelin
Demyelination
______________ in the PNS are capable of remyelinating the axon.
Schwann cells
Acute, massive exposures to lead would result in severe ____________, and intramyelinic edema
cerebral edema
Chronic lead intoxication usually leads to ________________, gastritis, or _________
peripheral neuropathy; anemia
Examples of chemicals associated with myelinopathies
hexachlorophene and tellurium
Neurotoxicant: Hexachlorophene
Neurologic findings: ____________, confusion, and ___________
Basis: _________ swelling, intramyelinic edema in _____ and _____, and _____ axonal degeneration
irritability; seizures
brain; CNS and PNS; late
Neurotoxicant: Tellurium
Neurologic finding: _____________, and hind limb paralysis in experimental animals
Basis: Demyelinating neuropathy, and ________________ in experimental animals
hydrocephalus
lipofuscinosis
Identify the neurotoxicant
When absorbed by the skin, it enters the nervous system and causes neurotoxicity by forming vacuoles that would create spongiosis in the brain
Hexachlorophene
Are primary means of defense in the CNS following exposure to neurotoxicants.
astrocytes
Modified T/F: Astrocytes also serves as spatial buffering system for osmotically active ions. They are also depot for metabolic processing of exogenous molecules only.
1st TRUE
2nd FALSE. depot for metabolic processing of endogenous molecules and xenobiotics
This causes astrocytic swelling and morphological changes
ammonia
The inhibition of neuronal glutamate precursor synthesis (changes in neurotransmitter uptake: glutamate) is a result of …?
increased intracellular ammonia
Organic nitrates, Dinitrobenzenes (DNB), and Metronidazole are classified as
Nitrochemicals
This nitrochemical creates gliovascular lesions that target astrocytes in the gray matter of the brainstem and deep cerebellar roof nuclei
dinitrobenzenes (DNB)
Prolonged treatment with this drug is associated with peripheral neuropathy; effects include paresthesia, headache, glossitis, urticaria or pruritus
metronidazole
This is an irreversible inhibitor of astrocyte-specific enzyme glutamine synthase in which there would be a large increase of glycogen levels that would lead to swollen and damaged astrocytic mitochondria
Methionine sulfoximine (MSO)
T/F: Although neurotransmitter-associated actions may be well understood for some agents, the specificity of the mechanism should not be assumed.
True
This neurotoxicant bind to nicotinic cholinergic receptor
nicotine
T/F:
Nicotine toxicity pathway: rapid rise after acute OD → excessive stimulation of nicotinic receptors → ganglionic paralysis (nausea, rapid heart rate, perspiration, somnolence, coma)
True
Cocaine blocks ____________, _____________, and ___________ reuptake at the nerve terminal in the CNS; causes release of dopamine from storage vesicles
dopamine; norepinephrine; serotonin
Modified T/F: Cerebrovascular defects, stroke, and intracranial hemorrhage are common effects of cocaine. The PRIMARY EVENT that is responsible for the addictive properties and euphoric feelings during cocaine intoxication is the blockade of the dopamine reuptake transporter (DAT)
BOTH TRUE
This neurotoxicant is involved in catecholamine neurotransmission in the CNS
amphetamines
This causes higher energy and sensation in adults
MDMA (methylenedioxymethamphetamine; ecstasy)
The most pronounced effects of amphetamines is on __________________, but can also damage serotonin axons and axon terminals.
dopaminergic neurons
These chemicals are associated with damages in the astrocytes
Ammonia, nitrochemicals, and methionine sulfoximine (MSO)
These chemicals are associated with neurotransmission-associated neurotoxicity
Cocaine, amphetamines, and nicotines
Neurotoxicant: amphetamine and metamphetamine
Neurologic findings: tremor, restlessness (acute), __________________ and hemorrhage, and _______________ disturbances
Basis: Bilateral infarcts of _______________, abnormalities in dopaminergic, serotonergic, and dopaminergic systems. Also acts at ________________ receptors in the PNS
cerebral infarctions; neuropsychiatric
globus pallidus, adrenergic
Neurotoxicant: Cocaine
Neurologic findings: Increased risk of stroke and ______________ in chronic users, increased risk of cardiac death; movement and psychiatric abnormalities especially during ______________
Decreased ____________ in fetal exposures (newborns)
Basis: Infarcts and hemorrhages, alteration in __________ dopamine neurotransmission
cerebral atrophy; withdrawal
head circumference
striatal
Neurotoxicant: Nicotine
Neurologic findings: nausea, vomiting, ____________
Basis: binds to nicotinic receptors (____________) low-dose stimulation; high-dose blocking
convulsions
cholinergic
Generalized depression of CNS function is produced by a variety of volatile solvents. Give examples
Ethanol, organics, and anesthetics
Mechanism of generalized depression: interactions with ____________ ion channels as well as ____________ calcium channels.
ligand-gated; voltage-gated
Modified T/F: Calcium is involved in motor function and control. Interactions with these compounds possibly induces NS depression
BOTH TRUE
Goal for future studies of neurotoxicology: replace standard _________ assessments with high throughput in vitro assays and ___________________________ to predict adverse outcomes.
In vivo; Quantitative Structure-Activity Relationships (QSARs)
T/F: The nervous system is the most complex system of the body.
True
T/F: There are still many gaps in understanding how many neurotoxins act, yet research is discovering their possible effects on the body’s structures and functions which may all be due to a lot of considerations.
True
T/F: It is important to understand that the most potent toxins are common kitchen ingredients, with extremely minute amounts sufficient to cause death.
False. Most potent toxins are neurotoxins
