J Clin Neurol.  2007 Dec;3(4):181-186. 10.3988/jcn.2007.3.4.181.

Oral Administration of Memantine Prolongs Survival in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

• Joo IS
• Hwang DH
• Seok JI
• Shin SK
• Kim SU

• KMID: 1808551
• DOI: http://doi.org/10.3988/jcn.2007.3.4.181

Abstract

BACKGROUND AND PURPOSE
N-methyl-D-aspartate (NMDA)-mediated neurotoxicity and oxidative stress have been implicated in the etiology of amyotrophic lateral sclerosis (ALS). Memantine is a low-affinity, noncompetitive NMDA receptor antagonist that may protect against motor neuron degeneration.
METHODS
Thirty transgenic mice expressing the G93A SOD1 mutation were randomly divided into control, low-dose memantine (30 mg/kg/day), and high-dose memantine (90 mg/kg/day) groups, with memantine supplied daily with drinking water beginning at 75 days of age. Body weight, survival, and behavioral performances including a rotarod test, paw grip endurance, and hindlimb extension reflex were assessed in the control and memantine-diet groups.
RESULTS
Clinical symptoms were evident in the G93A transgenic mice by 11 weeks of age. Memantine was tolerated well. Compared to control, mice treated with memantine performed better in the rotarod test and hindlimb extension reflex. Moreover, low-dose memantine treatment significantly prolonged the survival of the transgenic mice relative to control mice (141 vs 134 days, p<0.05).
CONCLUSIONS
These findings suggest that memantine, even when administered at the time of symptom onset, has beneficial effects on patients with ALS.

Keyword

Amyotrophic lateral sclerosis; Memantine; N-methyl-D-aspartate receptor antagonist

MeSH Terms

Administration, Oral*
Amyotrophic Lateral Sclerosis*
Animals
Body Weight
Drinking Water
Hand Strength
Hindlimb
Humans
Memantine*
Mice
Mice, Transgenic*
Motor Neurons
N-Methylaspartate
Oxidative Stress
Reflex
Rotarod Performance Test
Drinking Water
Memantine
N-Methylaspartate

Figure

• 

  Figure 1 Effects of memantine treatment on motor performance in G93A transgenic mice. Cumulative probability of the onset of deficit in rotarod (A), paw grip endurance (PaGE) (B), and extension reflex (C) tests. There was a trend toward an improved rotarod performance and delayed loss of extension reflex, although the effect was not statistically significant. Memantine had no effect on PaGE.

• 

  Figure 2 Cumulative probabilities for survival in animals treated with low-dose memantine (30 mg/kg/day), high-dose memantine (90 mg/kg/day), or water alone, starting at symptom onset at 75 days of age. Mortality was significantly delayed in G93A transgenic mice receiving low-dose memantine (p<0.05).

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