Florida International University
University Graduate School
Master’s Thesis Defense
Abstract
Claude Henry Volmar
Muñoz-Montaño and colleagues (1997) have suggested that lithium be considered as a treatment for Alzheimer’s disease (AD) because of its inhibition of glycogen synthase kinase 3-b-induced hyperphosphorylation of tau protein. Hyperphosphorylated tau protein is the major constituent of neurofibrillary tangles (NFTs), and NFTs are a hallmark of AD. This study provides the foundation for analyzing, in C57B6J mice, the therapeutic implications for lithium in AD. This is accomplished using Morris water maze tasks for spatial memory assessment combined with histological methods for cell death analysis.
Preliminary behavioral data of lithium treated (n=3) versus non-lithium treated control (n=3) animals reveal a positive effect from lithium after 24 hours of treatment. Further investigation of lithium treated (n=11) and controls (n=6) did not replicate the same early results. The data shows a significant negative effect of lithium on learning and on spatial memory after 24 hours. The data also reveal that after long-term treatment (5months), lithium has a positive effect on learning and spatial memory. Data obtained in this thesis from in situ DNA fragmentation detection on micro-sections of both treated and control animals suggest that lithium may also be acting on memory by protecting cells against apoptosis.
Despite lithium use in manic-depressive illness, its neuro-pharmacology and biochemical pathways are not fully known nor understood. The present data supports the hypothesis that lithium may be acting on memory via the cyclic AMP responsive element binding (CREB) protein pathway. Although lithium has been correlated with cytoprotective effects on neurons, these alone may not account for the significant effect on memory observed after long-term treatment. A model for the action of lithium on the central nervous system is proposed in this thesis. The use of lithium as a treatment for AD may need to be revisited.
|
Date: November 26, 2001 |
Department: Biological Sciences |
|
Time: 3:30 p.m. |
Major Professor: Dr. Ophelia I. Weeks |
|
Place: WC 130 |
|