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Neuroprotection by memantine against neurodegeneration induced by beta-amyloid(1-40)


Year of Publication:
Contact PI Name:
Javier Miguel-Hidalgo
Contact PI Affiliation:
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, USA
X.A. Alvarez, R. Cacabelos, G. Quack
Primary Reference (PubMED ID):
Funding Source:
Not Reported
Study Goal and Principal Findings:

In this study the authors tested the hypothesis that treatment with the NMDA receptor antagonist memantine is protective against beta -amyloid neurotoxicity and learning impairment in rats recieving an intra cerebral injection of beta amyloid peptide 1-40 (Abeta 1-40). Sprague–Dawley rats received vehicle or vehicle plus memantine s.c. by osmotic pump for 9 days. After 2 days of treatment, 2 ml of water containing Abeta (1–40) were injected into the hippocampal fissure. After 9 days of further treatment animals were tested for psychomotor activity and spatial discrimination then sacrificed and examined for neuronal degeneration, astrocytic and microglial activation. Abeta(1-40), but not water, injections into hippocampus led to neuronal loss in the CA1 subfield, evidence of widespread apoptosis, and astrocytic and microglial activation and hypertrophy.The memantine treated animals had significant reductions in the amount of neuronal degeneration, pyknotic nuclei, and markers of glial activation as compared with vehicle treated animals. Memantine treatment  however did not significantly alter motor activity or spatial learning compared to vehicle. These data suggest that memantine, at therapeutically relevant concentrations, can protect against neuronal degeneration induced by beta-amyloid. The authors concluded that in order  to further ascertain the relevance of memantine treatment for neuroprotection against long term Aβ-induced neurodegeneration future studies with longer survival times after amyloid deposition and longer periods of memantine treatment will be required.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
Therapeutic Target:
NMDA Receptor

Animal Model

Model Information:
Model Type:
beta Amyloid Peptide Injection
Strain/Genetic Background:
Not Applicable

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest
Experiment Notes

In studies using rats, typically the rat weight is reported rather than age. A female Sprague Dawley rat weighing 240-260g is between 10-12 weeks old (


Outcome Measured
Outcome Parameters
T Maze
Motor Function
Locomotor Activity
Rotarod Test
Pyknotic/Fragmented Nuclei
beta Amyloid Deposits
Activated Microglia
Activated Astrocytes
Microtubule-Associated Protein 2 (MAP2)
Drug Concentration-Plasma