Implications of the neuroprotective effects of lithium for the treatment of bipolar and neurodegenerative disorders.
Bipolar disorder is increasingly recognized as an illness that may progress to impairment in neurocognitive functioning and cell loss in cortical and limbic brain regions. Glutamatergic damage and/or damage due to high glucocorticoid levels that inhibit adult neurogenesis are likely contributing mechanisms. Drug treatments with possible neuroprotective effects are becoming increasingly important both clinically and as research tools. Mood stabilizing drugs and lithium in particular may act to prevent neuronal damage and tissue loss that may occur in the brain of patients with bipolar disorders. Lithium has been shown to exert neuroprotective effects in vitro and to stimulate neurogenesis in the hippocampus. Animal studies have demonstrated pharmacological effects of lithium suggestive of its role in neuroprotection, which range from reducing excitotoxicity through increased glutamate uptake, to regulation of a number of signal transduction intermediates such as myo-inositol, protein kinase C, phosphotidylinositol-3 kinase (PI-3K)/protein kinase B (Akt), ras-mitogen-activated protein kinase (MAPK), glycogen synthase kinase (GSK)-3alpha and -3beta and calcium. It remains to be established whether lithium treatment protects against possible cell damage in the same manner as it protects against recurrences of the illness. We propose to examine the effect of long-term lithium treatment on neurocognitive functioning of bipolar patients and the use of lithium in the treatment of chronic neuropsychiatric disorders.
Bauer
M
M
Department of Psychiatry and Psychotherapy, Charité - University Medicine Berlin, Campus Charité-Mitte (CCM), Berlin, Germany. michael.bauer@charite.de
Alda
M
M
Priller
J
J
Young
L T
LT
D000544:Alzheimer Disease / Q000188:drug therapy; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000473:pathology; D005938:Glucocorticoids / Q000009:adverse effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy; D018020:Lithium Compounds / Q000627:therapeutic use*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000517:prevention & control; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
D005938:Glucocorticoids; D018020:Lithium Compounds; D018696:Neuroprotective Agents; D018698:Glutamic Acid