Erdö SL, Schäfer M. Memantine is highly potent in protecting cortical cultures against excitotoxic cell death evoked by glutamate and N-methyl-D-aspartate. Eur J Pharmacol 198: 215-217
Department of Anatomy, Georg-August-University, Göttingen, F.R.G. European Journal of Pharmacology
(Impact Factor: 2.53).
07/1991; 198(2-3):215-7. DOI: 10.1016/0014-2999(91)90625-Z
The capacity of memantine to protect cultured cerebrocortical cells against N-methyl-D-aspartate (NMDA)- and glutamate-induced cell death was examined. Excitotoxic cell death was evaluated by phase contrast microscopy and quantified by estimating the release of lactic dehydrogenase from damaged cells. Memantine showed a strong, long-lasting and concentration-dependent protective effect against the excitotoxic damage induced by glutamate and NMDA, with almost complete protection being attained at a memantine concentration of 0.1 mM. The present findings indicate that memantine has potential value as a drug against excitotoxic brain damage.
Available from: William Ted Brown
- "After 5–7 days in vitro (DIV) CGCs were used for the experiments reported in the present study. When required, the CGCs were treated for 72 h with memantine (Sun Pharma) at a concentration of 100 µM, referred from the literature , . "
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ABSTRACT: Although the pathogenic mechanisms that underlie autism are not well understood, there is evidence showing that metabotropic and ionotropic glutamate receptors are hyper-stimulated and the GABAergic system is hypo-stimulated in autism. Memantine is an uncompetitive antagonist of NMDA receptors and is widely prescribed for treatment of Alzheimer's disease treatment. Recently, it has been shown to improve language function, social behavior, and self-stimulatory behaviors of some autistic subjects. However the mechanism by which memantine exerts its effect remains to be elucidated. In this study, we used cultured cerebellar granule cells (CGCs) from Fmr1 knockout (KO) mice, a mouse model for fragile X syndrome (FXS) and syndromic autism, to examine the effects of memantine on dendritic spine development and synapse formation. Our results show that the maturation of dendritic spines is delayed in Fmr1-KO CGCs. We also detected reduced excitatory synapse formation in Fmr1-KO CGCs. Memantine treatment of Fmr1-KO CGCs promoted cell adhesion properties. Memantine also stimulated the development of mushroom-shaped mature dendritic spines and restored dendritic spine to normal levels in Fmr1-KO CGCs. Furthermore, we demonstrated that memantine treatment promoted synapse formation and restored the excitatory synapses to a normal range in Fmr1-KO CGCs. These findings suggest that memantine may exert its therapeutic capacity through a stimulatory effect on dendritic spine maturation and excitatory synapse formation, as well as promoting adhesion of CGCs.
PLoS ONE 05/2012; 7(5):e36981. DOI:10.1371/journal.pone.0036981 · 3.23 Impact Factor
Available from: Anne Bertrand
- "The effect of memantine as NMDA antagonist was less pronounced than that of dizocilpine (MK801) but memantine well ameliorated hypoxic ischaemic damage following bilateral carotid occlusion and hypoxia (Chen et al. 1992). Also at clinically relevant doses, memantine markedly increased Brain Derived Neurotrophic Factor mRNA levels in rat limbic cortex (Erdo and Schafer 1991). Riluzol was also shown to dose dependently reduce the loss of primary rat mesencephalic cultures and human dopaminergic neuroblastoma caused by exposure to MPP + (Storch et al. 2000). "
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ABSTRACT: J. Neurochem. (2010) 113, 1459–1470.
The present experiments aimed at understanding the functional link between dopamine (DA) and glutamate (GLU) during the compensatory processes taking place after partial DA denervation. Lesion of the lateral part of substantia nigra in rats using 6-hydroxydopamine resulted in DA denervation of the lateral region of the ipsilateral caudate/putamen complex (CPc) whereas the medial CPc was spared. In vivo voltammetry revealed a large increase of extracellular dopamine (DAext) in the medial CPc both ipsilateral and contralateral to the lesion. In addition, in vivo microdialysis and HPLC-ED revealed a concomitant increase of extracellular glutamate (GLUext) in the ipsilateral medial CPc. Post-lesion chronic treatment with the putative neuroprotectors amantadine, memantine, and riluzole counteracted the tonic increases of DAext and GLUext, revealing a possible role of GLU neurotransmission in the DA over-expression. Finally, acute low doses of GBR12909 had no effect on the DAext in sham- operated animals, but dramatically increased DAext in lesioned animals. The data suggest that a partial unilateral nigral lesion induces a bilateral increase of DA turn-over in the non-denervated striata through GLU afferences to the DA terminals.
Journal of Neurochemistry 03/2010; 113(6):1459-70. DOI:10.1111/j.1471-4159.2010.06682.x · 4.28 Impact Factor
Available from: Chang-Joo Park
- "In addition, memantine treatment is effective when initiated after injury. This novel protective effect of memantine against white matter injury in vivo is consistent with many reports of neuronal protection by memantine in vivo in rodent ischemia models (Block and Schwarz, 1996; Chen et al., 1998; Stys and Lipton, 2007), and in vitro against glutamate-and NMDA-induced death (Erdö and Schäfer, 1991). Memantine, like MK-801, is an uncompetitive antagonist but exerts a use-dependent NMDAR blockade because of a faster off-rate than MK-801, and consequently exhibits less toxicity (Chen et al., 1992; Chen and Lipton, 2006). "
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ABSTRACT: Hypoxia-ischemia (H/I) in the premature infant leads to white matter injury termed periventricular leukomalacia (PVL), the leading cause of subsequent neurological deficits. Glutamatergic excitotoxicity in white matter oligodendrocytes (OLs) mediated by cell surface glutamate receptors (GluRs) of the AMPA subtype has been demonstrated as one factor in this injury. Recently, it has been shown that rodent OLs also express functional NMDA GluRs (NMDARs), and overactivation of these receptors can mediate excitotoxic OL injury. Here we show that preterm human developing OLs express NMDARs during the PVL period of susceptibility, presenting a potential therapeutic target. The expression pattern mirrors that seen in the immature rat. Furthermore, the uncompetitive NMDAR antagonist memantine attenuates NMDA-evoked currents in developing OLs in situ in cerebral white matter of immature rats. Using an H/I rat model of white matter injury, we show in vivo that post-H/I treatment with memantine attenuates acute loss of the developing OL cell surface marker O1 and the mature OL marker MBP (myelin basic protein), and also prevents the long-term reduction in cerebral mantle thickness seen at postnatal day 21 in this model. These protective doses of memantine do not affect normal myelination or cortical growth. Together, these data suggest that NMDAR blockade with memantine may provide an effective pharmacological prevention of PVL in the premature infant.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 07/2008; 28(26):6670-8. DOI:10.1523/JNEUROSCI.1702-08.2008 · 6.34 Impact Factor
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