title: Lithium prevents parkinsonian behavioral and striatal phenotypes in an aged parkin mutant transgenic mouse model.
abstract: Lithium has long been used as a treatment for the psychiatric disease bipolar disorder. However, previous studies suggest that lithium provides neuroprotective effects in neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease. The exact mechanism by which lithium exerts these effects still remains unclear. In the present study, we evaluated the effects of low-dose lithium treatment in an aged mouse model expressing a parkin mutation within dopaminergic neurons. We found that low-dose lithium treatment prevented motor impairment as demonstrated by the open field test, pole test, and rearing behavior. Furthermore, lithium prevented dopaminergic striatal degeneration in parkin animals. We also found that parkin-induced striatal astrogliosis and microglial activation were prevented by lithium treatment. Our results further corroborate the use of this parkin mutant transgenic mouse line as a model for PD for testing novel therapeutics. The findings of the present study also provide further validation that lithium could be re-purposed as a therapy for PD and suggest that anti-inflammatory effects may contribute to its neuroprotective mechanisms.
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lieu
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, USA.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Dewey
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, USA.
authors.forename: Shankar J
authors.initials: SJ
authors.lastname: Chinta
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Rane
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, USA.
authors.forename: Subramanian
authors.initials: S
authors.lastname: Rajagopalan
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Batir
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, USA.
authors.forename: Yong-Hwan
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Buck Institute for Research on Aging, Novato, CA, USA. Electronic address: jandersen@buckinstitute.org.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Andersen
mesh_terms: D000375:Aging; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics; D013378:Substantia Nigra / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D008094:Lithium; D004298:Dopamine
keywords: Astrocyte; Behavior; Lithium; Neuroinflammation; Parkinson’s disease; Striatum