PMID- 23793101
OWN - NLM
STAT- MEDLINE
DCOM- 20140401
LR  - 20211021
IS  - 1432-1912 (Electronic)
IS  - 0028-1298 (Linking)
VI  - 386
IP  - 10
DP  - 2013 Oct
TI  - Differential effects of glycogen synthase kinase 3 (GSK3) inhibition by lithium 
      or selective inhibitors in the central nervous system.
PG  - 893-903
LID - 10.1007/s00210-013-0893-9 [doi]
AB  - Glycogen synthase kinase (GSK3) is a constitutively active serine-threonine 
      kinase associated to neurological and psychiatric disorders. GSK3 inhibition is 
      considered a mediator of the efficacy of the mood-stabiliser lithium. This study 
      aimed at comparing the central nervous system effect of lithium with the 
      selective GSK3 inhibitors AZ1080 and compound A in biochemical, cellular, and 
      behavioural tests. Collapsin response mediator protein 2 is a neuron-specific 
      GSK3 substrate. Lithium, AZ1080, and compound A inhibited its phosphorylation in 
      rat primary neurons with different pIC50. After systemic treatments with lithium 
      or GSK3 inhibitors to assess specific functional responses, phosphorylation was 
      unchanged in adult rat brain, while it was strongly inhibited by GSK3 inhibitors 
      in pups, differently from lithium. Lithium may exert neurotrophic effect by 
      increasing brain-derived neurotrophic factor (BDNF) levels: in the present 
      experimental conditions, lithium exerted opposite effects on plasma BDNF levels 
      compared to GSK3 inhibitors, suggesting this effect might not be necessarily 
      mediated by GSK3 inhibition alone. While plasma thyroid-stimulating hormone and 
      luteinising hormone were not affected by lithium, they were decreased by 
      selective inhibitors. GH and prolactin displayed similar responses towards 
      reduction. Follicle-stimulating hormone levels were not altered by treatments, 
      whereas melatonin was specifically increased by AZ1080. Lithium impaired mouse 
      spontaneous locomotion and decreased amphetamine-induced hyper-locomotion. AZ1080 
      had no effects on locomotion, while compound A reduced spontaneous locomotor 
      activity without effects on amphetamine-induced hyper-locomotion. The present 
      results indicate that a broad correlation between the effects of lithium and 
      selective GSK3 inhibitors could not be devised, suggesting alternative 
      mechanisms, whereas overlapping results could be obtained in specific assays.
FAU - Caberlotto, Laura
AU  - Caberlotto L
AD  - Neurosciences CEDD, GlaxoSmithKline Medicines Research Centre, Via Fleming, 4, 
      37135, Verona, Italy.
FAU - Carboni, Lucia
AU  - Carboni L
FAU - Zanderigo, Floriana
AU  - Zanderigo F
FAU - Andreetta, Filippo
AU  - Andreetta F
FAU - Andreoli, Michela
AU  - Andreoli M
FAU - Gentile, Gabriella
AU  - Gentile G
FAU - Razzoli, Maria
AU  - Razzoli M
LA  - eng
PT  - Journal Article
DEP - 20130622
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Hormones)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Lithium Compounds)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (collapsin response mediator protein-2)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/metabolism
MH  - Cells, Cultured
MH  - Gastric Emptying/drug effects
MH  - Glycogen Synthase Kinase 3/*antagonists & inhibitors
MH  - Hormones/blood
MH  - Intercellular Signaling Peptides and Proteins
MH  - Lithium Compounds/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Motor Activity/drug effects
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurons/drug effects/metabolism
MH  - Protein Kinase Inhibitors/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2013/06/25 06:00
MHDA- 2014/04/02 06:00
CRDT- 2013/06/25 06:00
PHST- 2013/03/01 00:00 [received]
PHST- 2013/06/04 00:00 [accepted]
PHST- 2013/06/25 06:00 [entrez]
PHST- 2013/06/25 06:00 [pubmed]
PHST- 2014/04/02 06:00 [medline]
AID - 10.1007/s00210-013-0893-9 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2013 Oct;386(10):893-903. doi: 
      10.1007/s00210-013-0893-9. Epub 2013 Jun 22.