Upregulation of 'peripheral-type' benzodiazepine receptors in the globus pallidus in a sub-acute rat model of manganese neurotoxicity.
Manganese neurotoxicity (MN) is a neurological disorder characterized by selective neuronal loss in the globus pallidus together with characteristic morphological changes known as Alzheimer type II astrocytosis. In order to understand the underlying mechanisms responsible for these processes, we studied early effects of this metal in a sub-acute rat model. Levels of manganese in the globus pallidus were increased by 81% after 1 day of treatment and elevated by 551% compared to controls after 4 days. In addition, manganese treatment led to a 60% increase in ptbr expression, and a 105% increase in levels of its product, the isoquinoline-carboxamide binding protein, a major constituent of the 'peripheral-type' benzodiazepine receptor (PTBR) that is localized to astrocytes, in this brain region after 4 days. These results indicate that PTBRs, and possibly neurosteroids, are an early response to manganese exposure and may play a major role in the pathophysiology of MN.
Hazell
Alan S
AS
Department of Medicine, Hôpital Saint-Luc, University of Montreal, Montreal, Quebec, Canada. alan.stewart.hazell@umontreal.ca
Normandin
Louise
L
Nguyen
Bich
B
Kennedy
Greg
G
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005911:Gliosis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008345:Manganese / Q000009:adverse effects*; D020149:Manganese Poisoning / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002352:Carrier Proteins; D012333:RNA, Messenger; D018079:Receptors, GABA; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D008345:Manganese