PMID- 19523343
OWN - NLM
STAT- MEDLINE
DCOM- 20100326
LR  - 20220330
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 18
IP  - 9
DP  - 2009
TI  - Review of lithium effects on brain and blood.
PG  - 951-75
LID - 10.3727/096368909X471251 [doi]
AB  - Clinicians have long used lithium to treat manic depression. They have also 
      observed that lithium causes granulocytosis and lymphopenia while it enhances 
      immunological activities of monocytes and lymphocytes. In fact, clinicians have 
      long used lithium to treat granulocytopenia resulting from radiation and 
      chemotherapy, to boost immunoglobulins after vaccination, and to enhance natural 
      killer activity. Recent studies revealed a mechanism that ties together these 
      disparate effects of lithium. Lithium acts through multiple pathways to inhibit 
      glycogen synthetase kinase-3beta (GSK3 beta). This enzyme phosphorylates and 
      inhibits nuclear factors that turn on cell growth and protection programs, 
      including the nuclear factor of activated T cells (NFAT) and WNT/beta-catenin. In 
      animals, lithium upregulates neurotrophins, including brain-derived neurotrophic 
      factor (BDNF), nerve growth factor, neurotrophin-3 (NT3), as well as receptors to 
      these growth factors in brain. Lithium also stimulates proliferation of stem 
      cells, including bone marrow and neural stem cells in the subventricular zone, 
      striatum, and forebrain. The stimulation of endogenous neural stem cells may 
      explain why lithium increases brain cell density and volume in patients with 
      bipolar disorders. Lithium also increases brain concentrations of the neuronal 
      markers n-acetyl-aspartate and myoinositol. Lithium also remarkably protects 
      neurons against glutamate, seizures, and apoptosis due to a wide variety of 
      neurotoxins. The effective dose range for lithium is 0.6-1.0 mM in serum and >1.5 
      mM may be toxic. Serum lithium levels of 1.5-2.0 mM may have mild and reversible 
      toxic effects on kidney, liver, heart, and glands. Serum levels of >2 mM may be 
      associated with neurological symptoms, including cerebellar dysfunction. 
      Prolonged lithium intoxication >2 mM can cause permanent brain damage. Lithium 
      has low mutagenic and carcinogenic risk. Lithium is still the most effective 
      therapy for depression. It "cures" a third of the patients with manic depression, 
      improves the lives of about a third, and is ineffective in about a third. Recent 
      studies suggest that some anticonvulsants (i.e., valproate, carbamapazine, and 
      lamotrigene) may be useful in patients that do not respond to lithium. Lithium 
      has been reported to be beneficial in animal models of brain injury, stroke, 
      Alzheimer's, Huntington's, and Parkinson's diseases, amyotrophic lateral 
      sclerosis (ALS), spinal cord injury, and other conditions. Clinical trials 
      assessing the effects of lithium are under way. A recent clinical trial suggests 
      that lithium stops the progression of ALS.
FAU - Young, Wise
AU  - Young W
AD  - W. M. Keck Center for Collaborative Neuroscience, Rutgers, State University of 
      New Jersey, Piscataway, NJ 08854, USA. wisey@mac.com
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20090513
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Antipsychotic Agents)
RN  - 9FN79X2M3F (Lithium)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Animals
MH  - Antipsychotic Agents/blood/*pharmacology/therapeutic use
MH  - Bipolar Disorder/drug therapy
MH  - Brain/*drug effects/pathology
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Humans
MH  - Lithium/blood/*pharmacology/therapeutic use
RF  - 342
EDAT- 2009/06/16 09:00
MHDA- 2010/03/27 06:00
CRDT- 2009/06/16 09:00
PHST- 2009/06/16 09:00 [entrez]
PHST- 2009/06/16 09:00 [pubmed]
PHST- 2010/03/27 06:00 [medline]
AID - CT-2065 [pii]
AID - 10.3727/096368909X471251 [doi]
PST - ppublish
SO  - Cell Transplant. 2009;18(9):951-75. doi: 10.3727/096368909X471251. Epub 2009 May 
      13.