Lithium inhibits aluminum-induced apoptosis in rabbit hippocampus, by preventing cytochrome c translocation, Bcl-2...

Area of Science:

• Neuroscience
• Cell Biology
• Toxicology

Background:

• Neuronal death models suggest lithium possesses neuroprotective properties.
• Aluminum maltolate is a neurotoxin that can induce apoptosis-regulatory protein changes in the brain.

Purpose of the Study:

• To investigate the effect of chronic lithium treatment on apoptosis-regulatory proteins in the hippocampus.
• To determine if lithium can prevent aluminum-induced neurotoxicity at the subcellular level.

Main Methods:

• Rabbits received intracisternal aluminum administration to induce neurotoxicity.
• Animals were pretreated with lithium carbonate in drinking water for 14 days.
• Apoptosis-regulatory proteins (cytochrome c, Bcl-2, Bcl-X(L), Bax), caspase-3 activity, and DNA fragmentation (TUNEL assay) were analyzed.

Main Results:

• Aluminum induced cytochrome c release, altered Bcl-2/Bcl-X(L) and Bax levels, activated caspase-3, and caused DNA fragmentation.
• Lithium pretreatment prevented aluminum-induced cytochrome c translocation.
• Lithium upregulated anti-apoptotic proteins (Bcl-2, Bcl-X(L)), downregulated pro-apoptotic Bax, abolished caspase-3 activity, and reduced DNA damage.

Conclusions:

• Lithium exhibits neuroprotective effects against aluminum-induced neurotoxicity in rabbit hippocampus.
• Lithium modulates apoptosis-regulatory proteins in both mitochondria and endoplasmic reticulum.
• The neuroprotective mechanism of lithium involves regulating subcellular apoptosis-controlling proteins.