Abstract

MOOD STABILIZERS UPREGULATE BRAIN NEUROPROTECTIVE FACTORS Brain-derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2) are neuroprotective. Their brain levels are decreased in bipolar disorder and Alzheimer disease. We showed that chronically administered mood stabilizers, carbamazepine or lamotrigine, increased brain BDNF and Bcl-2 mRNA and protein levels. These changes may explain why mood stabilizers are neuroprotective, and might be used different progressive human brain diseases (Chang et al., 2009). PHOSPHOADENOSINE PHOSPHATE PHOSPHATASE IS NOT A TARGET OF LITHIUM Lithium, which is approved for treating patients with bipolar disorder, is reported to inhibit 3'(2')-phosphoadenosine-5'-phosphate (PAP) phosphatase activity. To test whether this inhibition is pharmacologically relevant to lithiums action, we fed rodents LiCl for 6 weeks, and then assayed brain. Lithium treatment did not change brain PAP phosphatase mRNA or protein, or increase PAP, indicating that the hypothesis was not applicable. A 25% reduced brain ADP/ATP ratio following lithium was in line with lithium's suggested neuroprotective action (Shaltiel et al., 2009).

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000145-10
Application #
8148191
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2010
Total Cost
$154,296
Indirect Cost

  Institution

Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Kim, H-W; Rapoport, S I; Rao, J S (2011) Altered arachidonic acid cascade enzymes in postmortem brain from bipolar disorder patients. Mol Psychiatry 16:419-28
Cheon, Yewon; Park, Jee-Young; Modi, Hiren R et al. (2011) Chronic olanzapine treatment decreases arachidonic acid turnover and prostaglandin E? concentration in rat brain. J Neurochem 119:364-76
Stolk, Pieter; Souverein, Patrick C; Wilting, Ingeborg et al. (2010) Is aspirin useful in patients on lithium? A pharmacoepidemiological study related to bipolar disorder. Prostaglandins Leukot Essent Fatty Acids 82:9-14
Lee, H-J; Rao, J S; Chang, L et al. (2010) Chronic imipramine but not bupropion increases arachidonic acid signaling in rat brain: is this related to 'switching' in bipolar disorder? Mol Psychiatry 15:602-14
Rapoport, Stanley I; Basselin, Mireille; Kim, Hyung-Wook et al. (2009) Bipolar disorder and mechanisms of action of mood stabilizers. Brain Res Rev 61:185-209
Rao, Jagadeesh S; Rapoport, Stanley I; Kim, Hyung-Wook (2009) Decreased GRK3 but not GRK2 expression in frontal cortex from bipolar disorder patients. Int J Neuropsychopharmacol 12:851-60
Rao, Jagadeesh S; Rapoport, Stanley I (2009) Mood-stabilizers target the brain arachidonic acid cascade. Curr Mol Pharmacol 2:207-14
Chang, Yunyoung C; Rapoport, Stanley I; Rao, Jagadeesh S (2009) Chronic administration of mood stabilizers upregulates BDNF and bcl-2 expression levels in rat frontal cortex. Neurochem Res 34:536-41
Shaltiel, G; Deutsch, J; Rapoport, S I et al. (2009) Is phosphoadenosine phosphate phosphatase a target of lithium's therapeutic effect? J Neural Transm (Vienna) 116:1543-9
Rapoport, Stanley I (2008) Brain arachidonic and docosahexaenoic acid cascades are selectively altered by drugs, diet and disease. Prostaglandins Leukot Essent Fatty Acids 79:153-6

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