Central nervous system toxicity of manganese: Mechanism of manganese concentration in the ventral mesencephalon

Persistent Link:
http://hdl.handle.net/10150/282218
Title:
Central nervous system toxicity of manganese: Mechanism of manganese concentration in the ventral mesencephalon
Author:
Ingersoll, Russell Taylor, 1966-
Issue Date:
1996
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
In the lateral choroid plexus, Mn was sequestered from the blood against a concentration gradient. Intrathecal administration of Mn²⁺ showed that the choroid plexus does not remove Mn from the cerebrospinal fluid and that intrathecal Mn²⁺ rapidly caused neurological abnormalities. Either 1 or 2 mg Mn²⁺/kg intrathecally resulted one day after dosage in a 91% and 95% decrease in the spontaneous motor activity of rats, respectively. Control activity was unchanged by intrathecal NaCl. Five days after administration, dopamine was decreased 70%; and Mn in the ventral mesencephalon was increased 14-fold as compared to controls. Mn in the central nervous system reached a maximum and dopamine reached a minimum 6 hours after 250 μg Mn²⁺/rat, intrathecally. The ventral mesencephalon contained more Mn than any other brain region (p < 0.001). Neurotransmitter reuptake carriers were inhibited in an effort to reduce the Mn concentration in the CNS. To inhibit neurotransmitter reuptake, rats were given cocaine i.p. and later Mn intrathecally. Mn²⁺ caused the ventral mesencephalon Mn concentration to increase from 0.57 μg/g to 31.8 μg/g. Cocaine prior to Mn decreased the concentration from 31.8 μg/g to 3.3 μg/g. To decrease neurotransmitter concentration, rats were given reserpine i.p. and later Mn intrathecally. Mn2+ caused the ventral mesencephalon Mn concentration increased from 0.77 μg/g to 29.9 μg/g. Reserpine prior to Mn decreased the concentration from 29.9 μg/g to 3.7 μg/g. Cocaine or reserpine decreased the Mn concentration in the occipital pole, frontal lobe and caudate putamen but not in the cerebellum. Manganese, cocaine or reserpine decreased the dopamine concentration in the caudate putamen from 10.5 to 6.3, 4.1 or 0.8 μg/g, respectively. The results suggest that intrathecal Mn²⁺ can rapidly cause dopaminergic specific neurotoxicity resulting in: (1) decreased spontaneous motor activity, (2) increased Mn concentration in the ventral mesencephalon and (3) decreased dopamine concentration in the caudate putamen. Mn concentration in the CNS is related to neurotransmitter uptake carriers since inhibiting reuptake or reducing concentrations of neurotransmitters resulted in decreased Mn concentrations in many brain regions.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Neuroscience.; Health Sciences, Toxicology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Pharmacology and Toxicology
Degree Grantor:
University of Arizona
Advisor:
Aposhian, H. Vasken; Montgomery, Erwin B., Jr.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleCentral nervous system toxicity of manganese: Mechanism of manganese concentration in the ventral mesencephalonen_US
dc.creatorIngersoll, Russell Taylor, 1966-en_US
dc.contributor.authorIngersoll, Russell Taylor, 1966-en_US
dc.date.issued1996en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractIn the lateral choroid plexus, Mn was sequestered from the blood against a concentration gradient. Intrathecal administration of Mn²⁺ showed that the choroid plexus does not remove Mn from the cerebrospinal fluid and that intrathecal Mn²⁺ rapidly caused neurological abnormalities. Either 1 or 2 mg Mn²⁺/kg intrathecally resulted one day after dosage in a 91% and 95% decrease in the spontaneous motor activity of rats, respectively. Control activity was unchanged by intrathecal NaCl. Five days after administration, dopamine was decreased 70%; and Mn in the ventral mesencephalon was increased 14-fold as compared to controls. Mn in the central nervous system reached a maximum and dopamine reached a minimum 6 hours after 250 μg Mn²⁺/rat, intrathecally. The ventral mesencephalon contained more Mn than any other brain region (p < 0.001). Neurotransmitter reuptake carriers were inhibited in an effort to reduce the Mn concentration in the CNS. To inhibit neurotransmitter reuptake, rats were given cocaine i.p. and later Mn intrathecally. Mn²⁺ caused the ventral mesencephalon Mn concentration to increase from 0.57 μg/g to 31.8 μg/g. Cocaine prior to Mn decreased the concentration from 31.8 μg/g to 3.3 μg/g. To decrease neurotransmitter concentration, rats were given reserpine i.p. and later Mn intrathecally. Mn2+ caused the ventral mesencephalon Mn concentration increased from 0.77 μg/g to 29.9 μg/g. Reserpine prior to Mn decreased the concentration from 29.9 μg/g to 3.7 μg/g. Cocaine or reserpine decreased the Mn concentration in the occipital pole, frontal lobe and caudate putamen but not in the cerebellum. Manganese, cocaine or reserpine decreased the dopamine concentration in the caudate putamen from 10.5 to 6.3, 4.1 or 0.8 μg/g, respectively. The results suggest that intrathecal Mn²⁺ can rapidly cause dopaminergic specific neurotoxicity resulting in: (1) decreased spontaneous motor activity, (2) increased Mn concentration in the ventral mesencephalon and (3) decreased dopamine concentration in the caudate putamen. Mn concentration in the CNS is related to neurotransmitter uptake carriers since inhibiting reuptake or reducing concentrations of neurotransmitters resulted in decreased Mn concentrations in many brain regions.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Neuroscience.en_US
dc.subjectHealth Sciences, Toxicology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorAposhian, H. Vaskenen_US
dc.contributor.advisorMontgomery, Erwin B., Jr.en_US
dc.identifier.proquest9720597en_US
dc.identifier.bibrecord.b34528313en_US
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