Ladostigil prevents age-related glial activation and spatial memory deficits in rats.
Oxidative stress and glial activation occur in the aging brain. Ladostigil is a new monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitor designed for the treatment of Alzheimer's disease. It has neuroprotective and antioxidant activities in cellular models at much lower concentrations than those inhibiting MAO or AChE. When ladostigil (1mg/kg/day) was given for 6 months to 16-month-old rats it prevented the age-related increase in activated astrocytes and microglia in several hippocampal and white matter regions and increased proNGF immunoreactivity in the hippocampus towards the levels in young rats. Ladostigil also prevented the age-related reduction in cortical AChE activity and the increase in butyrylcholinesterase activity in the hippocampus, in association with the reduction in gliosis. The immunological and enzymatic changes in aged rats were associated with improved spatial memory. Ladostigil treatment had no effect on memory, glial or proNGF immunoreactivity in young rats. Early treatment with ladostigil could slow disease progression in conditions like Alzheimer's disease in which oxidative stress and inflammatory processes are present.
Weinstock
Marta
M
Department of Pharmacology, School of Pharmacy, Hebrew University Medical Center, Ein Kerem, Jerusalem 91120, Israel. martar@ekmd.huji.ac.il
Luques
Lisandro
L
Poltyrev
Tatyana
T
Bejar
Corina
C
Shoham
Shai
S
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D002802:Cholinesterases / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000473:pathology / Q000517:prevention & control*; D008995:Monoamine Oxidase / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects*; D013997:Time Factors
C423264:(N-propargyl-(3R) aminoindan-5-yl)-ethyl methyl carbamate; D007189:Indans; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D011498:Protein Precursors; C514218:pro-nerve growth factor, rat; D008995:Monoamine Oxidase; D002802:Cholinesterases