ULTIMATE COMPUTING - Quantum Consciousness Studies

Cytoskeleton/Cytocomputer 125
the mitotic spindle poisons are effective against malignancy. However, they can
cause side effects including peripheral nerve damage by injuring MT dependent
axoplasmic transport. This results in peripheral nerve damage in many patients
who receive the anti-microtubule drugs. Sometimes severe neurological
dysfunction limits the use of the vinca drugs. Fortunately, neither vinca alkaloids
nor colchicine cross the blood brain barrier so central nervous system problems
are limited.
No agents are known to selectively disrupt intermediate filaments (although
2,5 hexane dione may act in this way). In intact cells, vanadate combined with
drugs that disassemble microtubules cause vimentin type intermediate filaments
to collapse around the nucleus. A toxin known as beta, beta prime
iminodiproprionitrile (IDPN) disrupts microtubule/neurofilament organization in
axons, which results in colocalization of certain MAP II subgroups with
intermediate filaments. Wisniewski and colleagues (1966) showed that injection
of aluminum salts into the brain or cerebrospinal fluid of experimental animals
induced marked accumulation of 10 nanometer filaments in cell bodies, dendrites
and initial axon segments of large neurons. When silver stained, these
accumulations superficially resemble the neurofibrillary tangles that are
encountered in a number of human disease states, notably Alzheimer’s disease,
Parkinsonism dementia and senility. The filamentous accumulations are not
precisely identical to those of the human diseases but raise interesting questions
about the role of cytoskeletal proteins in these afflictions. Alzheimer’s disease
and related forms of senile dementia are characterized by these neurofibrillary
tangles which result in various symptoms including a shortage of acetylcholine at
synapses of “cholinergic” neurons. This shortage may be due to a breakdown in
the cytoskeletal transport mechanisms which deliver acetylcholine precursors to
the synapses. The cognitive dysfunction which characterizes the dementias is
somehow related to disruption of the cytoskeleton. Other toxins whose
mechanisms have been ascribed to cytoskeletal effects include hexanedione and
hexacarbons, carbon disulfide, acrylamide, methylmercury, and mineral fiber
asbestos.
When cells are injured by lack of oxygen, acidosis, toxins, or other causes,
there is an irreversible point beyond which cell death is inevitable. Recent
evidence points to a pathological elevation of cytoplasmic calcium ion as the
irreversible point (Farber, 1981). The excess calcium may originate outside the
cell, diffusing across damaged membranes, or may be released from cytoplasmic
reservoirs including the cytoskeleton. Regardless of its source, the elevated
calcium causes depolymerization of microtubules and other cytoskeletal
components. The net result is a loss of cytoplasmic organization, enzyme
function, and structural integrity leading to cell death. Dimethysulfoxide (DMSO)
is a solvent which stabilizes polymerized microtubules, and which has been
shown to preserve integrity of cells and tissues against damaging effects of
radiation, low temperature, and other insults. Other compounds (taxol, polylysine,
etc.) also fortify or preserve MT and the cytoskeleton and could be
important in future therapies.
The effects of a number of other drugs may be mediated via the cytoskeleton;
among these are anesthetics which cause a reversible cessation of consciousness.
In the 19th century, Claude Bernard noted that an anesthetic (chloroform)
inhibited “protoplasmic streaming” in slime molds, a function of the cytoskeleton.
Allison and Nunn (1968) showed that sufficient concentrations of the general
anesthetic halothane reversibly depolymerized MT. Sleep producing barbiturates,
local anesthetics, and major tranquilizers such as thorazine also bind to brain MT.
Chapter 7 will describe how anesthesia is related to inhibition of cooperative