Cytology of the Nervous System Flashcards
Lewy Body
eosinophilic cytoplasmic inclusions of degenerating neurons in the substantia nigra, pars compacta in patients with Parkinson’s and in cortical and brainstem neurons in patients with certain forms of dementia
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Nigri bodies
eosinophilic cytoplasmic inclusions seen in degenerating neurons in the hippocampus and cerebellar cortex in patients with rabies
Tau protein
cross links microtubules
in certain neurodegenerative diseases of the CNS it becomes excessively phosphorylated which prevents cross linking. The affected microtubules form helical filaments which progress to neurofibrillary tangles and senile plaques in the cell body ad dendrites of neurons
Neurofibrillary tangles
prominent features of degenerating neurons in ALzheimers disease, amytrophic lateral sclerosis, and Down
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Alzheimer’s
neurons in the limbic system, cholinergic neurons in the basal nucleus of Meynert, and neurons in the cerebral cortex and preferentially affected
Loss of dendritic spines
progressive loss occurs with aging and severe loss is associated with cognitive disorders
significant absence of spines in many t ypes of neurons in patients with Down
Disruption of fast anterograde transport
may result in an axonal polyneuropathy and may be cause by anoxia which reflects mitochondrial oxidative phosphorylations, or by anticancer agents such as colchicine and vinblastine which depolymerize microtubules
Diabetes and axonal transport
hyperglycemia results in an alteration of proteins that form microtubules which may disrupt axonal transport
patients may develop axonal polyneuropathies in long axons in nerves that produce a “glove and stocking” pattern of altered sensation and pain in the feet and then in the hands
Retrograde disease infiltration
polio
herpes
rabies
tetanus
retrogradely transported by axons that innervate skeletal muscle
Polio and rabies weakness
patients may have weakness of skeletal muscles innervated by affected neurons
Tetanus signs
continuous contractions and spasms of axial and limb muscles and spasms of muscles innervated by certain cranial nerves
Herpes transport
taken up and retrogradely transported in SENSORY fibers and remains dormant in sensory ganglia
Herpes and rabies special feature
both are also transported anterograde
when activated the herpes virus results in painful vesicles corresponding to the distribution of the affected sensory fibers
rabies is transported to salivary glands and is transmitted by saliva after an animal bite
a skunk bit is the most common cause of rabies in US
Gap junctions
gap junctions close in damaged neurons and decouple the damaged cells from other neurons in response to a decrease in intracellular pH or elevated intracellular calcium (as in glutamate induced excitatoxicity)
Organophosphates
mustard gas and insecticides
binds irreversibly to acetylcholinesterase at the NMJ
ACh accumulates in the synaptic cleft and causes prolonged depolarization of skeletal muscle making it less sensitive to additional ACh release. Death may result from respiratory paralysis
Cholinergic neurons in Alzheimer’s
in the CNS, cholinergic neurons in the ventral forebrain (basal nucleus of Meynert) are a main type of neuron that degenerates
Glutamate induce excitotoxicity
ichemic neurons in stroke patients may have glutamate induced excitotoxicity in which glutamate accumulations in the synaptic cleft because the uptake process is energy dependent and is slowed by oxygen deprivation
Epilepsy (multiple seizures that arise from excessive neuronal activity in the cerebral cortex) may also cause glutamate induced excitotoxicity of GABA neurons, increasing the likelihood of additional seizures
What causes excessive glutamate levels
result from an increase in the influx of calcium into the postsynaptic cell at NMDA receptors. The influx of calcium may result in the production of free radicals in the postsynaptic cell which damages the membranes of its organelles and the plasma membrane. Disruption of the plasma membrane results in an influx of water, which leads to swelling and eventual cell lysis
*Blockage of NMDA calcium receptors that respond to glutamate may be effective in reducing neuronal loss in stroke patients
Antianxiety medications
Benzodiazepines are effective drugs that act by enhancing the effects of GABA neurons. Benzos and barbiturates also act as anti epileptic drugs by enhancing GABA inhibition
Selective loss of dopaminergic neurons in substantia nigra
results in Parkinson’s disease, a motor disorder of basal ganglia
Dopamine in schizophrenia
changes in the levels of dopamine in the mesolimbic and mesocortical circuits may result in the positive and negative symptoms of schizophrenia, respectively
Dopamine and drugs
cocaine and amphetamines are addictive substances that act by increasing dopamine levels, particularly in the mesolimbic pathway
Depression
changes in the synthesis, release, or activation of catecholamines and serotonin may cause depression, or bipolar disorder, during which patients experience both depression and euphoric episodes
antidepressant drugs include MAO inhibitors which limit the reuptake of catecholamines. Drugs such as prozac selectively block the uptake of serotonin without affecting the reuptake of other catecholamines, and tricyclic compounds (for severe depression) inhibit the uptake of both serotonin and norepinephrine
Botulinum toxin
prevents the release of ACh by binding to the presynaptic membrane at the NMJ and at preganglionic autonomic terminals
both skeletal and smooth muscles are affected
patients have weakness initially in muscles innervated by cranial nerves and then weakness in the limbs. Patients also have a dry mouth and abdominal cramping, vomiting, and diarrhea because of an absence of peristalsis