Linked Life Data

19619614

Source:http://linkedlifedata.com/resource/pubmed/id/19619614

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-9-18
pubmed:abstractText
Lithium is an efficacious drug for the treatment of mood disorders, and its application is also considered a potential therapy for brain damage. However, the mechanisms underlying lithium's therapeutic action and toxic effects in the nervous system remain largely elusive. Here we report on the use of a versatile genetic model, the fruit fly Drosophila melanogaster, to discover novel molecular components involved in the lithium-responsive neurobiological process. We previously identified CG15088, which encodes a putative nutrient amino acid transporter of the solute carrier 6 (SLC6) family, as one of the genes most significantly upregulated in response to lithium treatment. This gene was the only SLC6 gene induced by lithium, and was thus designated as Lithium-inducible SLC6 transporter or List. Either RNA interference (RNAi)-mediated knockdown or complete deletion of List resulted in a remarkable increase in the susceptibility of adult flies to lithium's toxic effects, whereas transgenic expression of wild-type List significantly suppressed the lithium hypersensitive phenotype of List-deficient flies. Other ions such as sodium, potassium and chloride did not induce List upregulation, nor did they affect the viability of flies with suppressed List expression. These results indicate that lithium's biochemical or physical properties, rather than general osmotic responses, are responsible for the lithium-induced upregulation of List, as well as for the lithium-susceptible phenotype observed in List knockdown flies. Interestingly, flies became significantly more susceptible to lithium toxicity when List RNAi was specifically expressed in glia than when it was expressed in neurons or muscles, which is consistent with potential glial expression of List. These results show that the List transporter confers resistance to lithium toxicity, possibly as a consequence of its amino acid transporter activity in CNS glia. Our results have provided a new avenue of investigation toward a better understanding of the molecular and cellular mechanisms that underlie lithium-responsive neurobiological process.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1873-7544
pubmed:author
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
825-37
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
A putative amino acid transporter of the solute carrier 6 family is upregulated by lithium and is required for resistance to lithium toxicity in Drosophila.
pubmed:affiliation
Department of Anesthesia, Carver College of Medicine, University of Iowa, 1-316 BSB, 51 Newton Road, Iowa City, IA 52242, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural