Lithium activates brain phospholipase A2 and improves memory in rats: implications for Alzheimer’s disease

Abstract

a significant perdurability of long-term memory, which correlated with increased transcriptional and enzymatic activities of certain members of the Pla2 family (iPla2 and sPla2) after the chronic lithium treatment. Our data suggest new possible targets of lithium, add more information on its pharmacological activity and reinforce the possible use of low doses of lithium for the treatment of neurodegenerative conditions such as the Alzheimer's disease.

Association of Lithium in Drinking Water With the Incidence of Dementia

“…Furthermore, long-term microdoses of lithium have compared with higher doses—a more prominent effect on membrane homeostasis (which may be disturbed in Alzheimer disease)—by activating forms of cytosolic phospholipase A2 and calcium-independent phospholipase A2 in primary cultures of cortical and hippocampal neurons . In addition, rats exposed to long-term (100 days) treatment with 125 mg/L of lithium in drinking water, which resulted in low mean (SD) blood lithium levels (0.1 [0.019] mEq/L), experienced activated brain phospholipase A2; this activation is required for memory retrieval and improved memory …”

“…45 In addition, rats exposed to long-term (100 days) treatment with 125 mg/L of lithium in drinking water, which resulted in low mean (SD) blood lithium levels (0.1 [0.019] mEq/L), experienced acti-vated brain phospholipase A2; this activation is required for memory retrieval and improved memory. 46 Other arguments that support the view that microlevels of lithium may affect human behavior derive from prior crosssectional studies 32,33 based on ecologic, nonindividualized data that report that levels of lithium in drinking water correlate inversely with the rate of suicide and from a preliminary study 47 on the effects of nutritional lithium supplementation on mood. However, a newly conducted Danish study, 26 which used individualized data as the present study did, did not confirm the protective effect of exposure to lithium in drinking water and the risk of suicide.…”

“Cell Membrane Theory of Senescence” and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications

“…Both PLA2 and AA are important for synaptic signaling, long-term potentiation (LTP), learning and memory [198][199][200][201][202]. Inhibition of PLA2 diminished memory especially specific inhibition of GVIA-PLA2 implying a role for AA [203][204][205]. Several types of stimuli that enhance neuronal activity also increase PLA2 activity and AA levels to enhance neuronal activity that, in turn, increase the production of Aβ (amyloid beta).…”

Rhodiola crenulata protects against Alzheimer's disease in rats: A brain lipidomics study by Fourier‐transform ion cyclotron resonance mass spectrometry coupled with high‐performance reversed‐phase liquid chromatography and hydrophilic interaction liquid chromatography

“…Moreover, the abnormal conduction function of APP can cause a neurotoxic effect, thereby exacerbating the development of AD. In addition, PLA2 blockers can effectively inhibit amyloid protein‐mediated neuronal synapse, which has been shown to be an early pathological feature of AD 38–40 . Therefore, the transmission of PLA2 is closely related to the pathogenesis of AD.…”