Impaired excitatory transmission in the striatum of rats chronically intoxicated with manganese.
Chronic exposure to manganese (Mn) is known to produce a parkinsonian or dystonic state in humans caused by a rather selective involvement of the basal ganglia. Experimental observations suggest that secondary excitotoxic mechanisms play a crucial role in the development of Mn-induced neurodegeneration in the striatum, although the site of interference of Mn with glutamatergic transmission in this brain area is still unknown. To answer this question, in the present in vitro study, we investigated the physiological characteristics of striatal excitatory synaptic transmission in a rat model of Mn intoxication. We found that chronic Mn greatly increased both frequency and amplitude of spontaneous excitatory postsynaptic potentials, in the absence of appreciable changes of intrinsic membrane properties of striatal cells. The sensitivity of striatal neurons to glutamate AMPA and NMDA receptor stimulation was unaffected by Mn poisoning, as demonstrated by comparing the membrane responses produced in control and treated rats to the application of selective agonists of these receptors and to the direct activation of corticostriatal glutamatergic fibers. In addition, also paired-pulse facilitation was unaltered by Mn treatment, indicating that this toxin does not affect the pre- and postsynaptic mechanisms responsible for the appearance of this short-term form of synaptic plasticity at corticostriatal synapses. It is concluded, therefore, that hyperactivity of corticostriatal neurons, rather than increased postsynaptic sensitivity to glutamate, accounts for the abnormal excitation of striatal neurons in the course of Mn intoxication.
Centonze
D
D
Clinica Neurologica, Dipartimento di Neuroscienze, Universita' "Tor Vergata,", Via di Tor Vergata 135, Rome, 00133, Italy.
Gubellini
P
P
Bernardi
G
G
Calabresi
P
P
D000818:Animals; D001921:Brain / Q000378:metabolism; D002540:Cerebral Cortex / Q000503:physiopathology; D002908:Chronic Disease; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D008099:Liver / Q000737:chemistry; D008297:Male; D008345:Manganese / Q000032:analysis; D020149:Manganese Poisoning / Q000503:physiopathology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013569:Synapses; D009435:Synaptic Transmission; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D008345:Manganese; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid