THE NANO-SKELETON IN THE CLOSETThe cells of the human body have different shapes. The shapes ensurethat the cell performs its function properly.In the brain the cytoskeleton plays a key role in maintaining the shapeof both neurons and glial cells. The shape is essential for neuronalphysiology including neurotransmission and synapse formation.Formation of new dendrites is also a function of the cytoskeletalreorganization.
A recent study reported on 1/24/12 (Medwire) suggests "that patientswith schizophrenia have regional alterations in the expression of anisoform of the cytoskeleton protein β-tubulin." Investigators "studied 110 postmortem brain tissue samples from thedorsolateral prefrontal cortex (DLPFC), the anterior cingulate cortex(ACC), the hippocampus (HC), and the superior temporal gyrus (STG)of elderly patients with schizophrenia and 103 from similarly agedmentally healthy individuals" and used Western blot analysis to find"that ACC tissue samples from schizophrenia patients showed asignificant decrease in βI expression compared with those fromcontrols" while "DLPFC tissue samples from schizophrenia patientsshowed a significant increase in βI expression compared with thosefrom controls."Aside from maintaining the cell shape and borders, neuronalcytoskeleton, especially microtubules, also transports proteins and cellorganelles from the center of the cell to the axon and denrites.The cytoskeleton of the neuron is comprised of three elements:-microtubules
-intermediate filaments-microfilamentsNeuronal microtubules consist of alpha and beta tubulin.These molecules are arranged in a circular form, creating hollowtubules used for transporting proteins and organelles along the axonand the dendrites.Several studies revealed that beta tubulin was decreased in the anteriorcingulate cortex(ACC) of patients with schizophrenia.Intermediate filaments are ropelike fibers of 8-12 nm in diameter. Theyare thought to provide mechanical strength to the cytoskeleton of bothneurons and glia.Microfilaments such as actin, spectrin and ankyrin are found both inboth neurons and glia. They are particularly concentrated inpresynaptic terminals, dendritic spines and growth cones. Because of
their proximity to the cell membrane they are thought to stabilize thetrans-membrane proteins such as cadherins that make the cell stick toeach other.Cumulative evidence suggests that neurodegenerative diseases andpsychiatric illnesses are associated with cytoskeletal alterations inneurons that in turn lose synaptic connectivity and the ability totransmit incoming axonal information to the somatodendritic domain.In neurodegenerative diseases, the cytoskeleton is abnormallyassembled and impairments of neurotransmission occurs.In Alzheimer’s disease, the neurofibrillary tangles are paired helicalfilaments consisting of microtubule-associated protein tau. Undernormal conditions tau binds to microtubules, stabilizing neuronalstructure and integrity. Excessive phosphorylation of tau is assumed tobe the cause of the formation of paired helical filaments –neurofibrillary tangles (NFT).
In Parkinson’s disease and Lewy body dementia, the Lewy bodies aremade of abnormal tubulin.In schizophrenia neuronal shape, loss of dendrites and spines as well asirregular distribution of neuronal elongations occur in specific brainareas leading to abnormal connections, thus abnormal connectomes.Adonis Sfera, MD