Selective vulnerability of pallidal neurons in the early phases of manganese intoxication.
Prolonged exposure to manganese in mammals may cause an extrapyramidal disorder characterized by dystonia and rigidity. Gliosis in the pallidal segments underlies the well-established phase of the intoxication. The early phase of the intoxication may be characterized by psychic, nonmotor signs, and its morphological and electrophysiological correlates are less defined. In a rat model of manganese intoxication (20 mg/ml in drinking water for 3 months), neither neuronal loss nor gliosis was detected in globus pallidus (GP). However, a striking vulnerability of manganese-treated GP neurons emerged. The majority of GP neurons isolated from manganese-treated rats died following brief incubation in standard dissociation media. In addition, patch-clamp recordings in the whole-cell configuration were not tolerated by surviving GP neurons. Neither coeval but untreated GP neurons nor striatal ones manifested analogous susceptibility. Using the perforated-patch mode of recording we attempted at identifying the functional hallmarks of GP vulnerability: in particular, voltage-gated calcium currents and glutamate-induced currents were examined. Manganese-treated GP neurons exhibited calcium currents similar to control cells aside from a slight reduction in the dihydropyridine-sensitive current facilitation. Strikingly, manganese-treated GP cells--but not striatal ones--manifested peculiar responses to glutamate, since repeated applications of the excitatory amino acid, at concentrations which commonly promote desensitizing responses, produced instead an irreversible cell damage. Possible mechanisms are discussed.
Spadoni
F
F
Dipartimento Neuroscienze, Università di Tor Vergata, Rome, Italy.
Stefani
A
A
Morello
M
M
Lavaroni
F
F
Giacomini
P
P
Sancesario
G
G
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D005917:Globus Pallidus / Q000187:drug effects* / Q000473:pathology*; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D020149:Manganese Poisoning / Q000473:pathology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
D015220:Calcium Channels; D018698:Glutamic Acid; D002118:Calcium