Lethal retrograde axoplasmic transport of doxorubicin (adriamycin) to motor neurons. A toxic motor neuronopathy.
نویسندگان
چکیده
Doxorubicin (Adriamycin) is an autofluorescent anthracycline antibiotic that acts as a DNA intercalator. Following intraneural microinjection of 3 micrograms of doxorubicin into rat tibial nerve, fluorescence microscopy indicated that it is transported retrogradely to anterior horn cell bodies. Subsequently, these motor neurons underwent a progressive subacute degeneration that occurred over a period of 35-39 days. Combined electrophysiological and neuropathological methods indicated that dorsal root ganglion cells were relatively unaffected by this dose of toxin. The selective motor neuron degeneration produced by this agent raises the possibility that abnormalities of nucleic acid metabolism may be involved in the aetiology of motor neuron diseases.
منابع مشابه
Dynein is the motor for retrograde axonal transport of organelles.
Vesicular organelles in axons of nerve cells are transported along microtubules either toward their plus ends (fast anterograde transport) or toward their minus ends (retrograde transport). Two microtubule-based motors were previously identified by examining plastic beads induced to move along microtubules by cytosol fractions from the squid giant axon: (i) an anterograde motor, kinesin, and (i...
متن کاملA quantitative study of retrograde axonal transport in motor and sensory neurons.
We used 3H N-succinimidyl propionate to covalently label in vivo proteins of the rat sciatic nerve, and studied the accumulation of radioactively labeled proteins in the cell bodies of the ipsilateral dorsal root ganglion and ventral horn of spinal cord to assess retrograde axonal transport in sensory and motor neurons respectively. In each case the early accumulation of a small amount of radio...
متن کاملDifferential effects of neurotrophic factors on motoneuron retrograde labeling in a murine model of motoneuron disease.
It has been shown that abnormalities in axonal transport occur in several mouse models with motoneuron degeneration and also in the human disease amyotrophic lateral sclerosis. In this report, we have examined the potential of neurotrophic factors to act on axonal transport properties in a mouse mutant, progressive motor neuronopathy (pmn). This mouse mutant has been characterized as a "dying-b...
متن کاملMissense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease
Progressive motor neuronopathy (pmn) mutant mice have been widely used as a model for human motoneuron disease. Mice that are homozygous for the pmn gene defect appear healthy at birth but develop progressive motoneuron disease, resulting in severe skeletal muscle weakness and respiratory failure by postnatal week 3. The disease starts at the motor endplates, and then leads to axonal loss and f...
متن کاملMyosin Va and microtubule-based motors are required for fast axonal retrograde transport of tetanus toxin in motor neurons.
Using a novel assay based on the sorting and transport of a fluorescent fragment of tetanus toxin, we have investigated the cytoskeletal and motor requirements of axonal retrograde transport in living mammalian motor neurons. This essential process ensures the movement of neurotrophins and organelles from the periphery to the cell body and is crucial for neuronal survival. Unlike what is observ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Brain : a journal of neurology
دوره 111 ( Pt 4) شماره
صفحات -
تاریخ انتشار 1988