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

Miguel-Hidalgo, José Javier; Alvarez, X.A.; Cacabelos, Ramón; Quack, G.

doi:10.1016/s0006-8993(02)03731-9

Cited by 259 publications

(154 citation statements)

References 53 publications

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“…79793). The amount of Aβ (0.5 nM/µl dissolved in 0.9% normal saline; pH = 8.0) was chosen based on our earlier experiment, and the solution was prepared according to a previously described protocol (Miguel-Hidalgo, Alvarez, Cacabelos, & Quack, 2002) and then immediately stored at -70 ˚C until used. Sham-operated rats received 4 l of 0.9% normal saline instead of Aβ solution.…”

Section: Methodsmentioning

confidence: 99%

Genistein ameliorates learning and memory deficits in amyloid β(1–40) rat model of Alzheimer’s disease

Bagheri

Joghataei

Mohseni

et al. 2011

Neurobiology of Learning and Memory

209

112

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Genistein ameliorates learning and memory deficits in amyloid beta ((1-40) AbstractAlzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by increased β-amyloid (Aβ) deposition and neuronal dysfunction leading to impaired learning and recall.Ageing, heredity, and induced oxidative stress are among proposed risk factors. The increased frequency of the disease in women also suggests a role for estrogen in development of AD. In the present study, effects of the phytoestrogen genistein (10 mg/kg) on learning and memory impairments was assessed in intrahippocampal A (1-40) -injected rats. The estrogen receptor antagonist fulvestrant was injected intracerebroventricularly in a group of A-lesioned rats. The A-injected animals exhibited the following: lower spontaneous alternation score in Y-maze tasks, impaired retention and recall capability in the passive avoidance test, and fewer correct choices and more errors in the RAM task. Genistein, but not genistein and fulvestrant, significantly improved most of these parameters. Measurements of oxidative stress markers in hippocampal tissue of A-injected rats showed an elevation of malondialdehyde (MDA) and nitrite content, and a reduction of superoxide dismutase (SOD) activity. Genistein significantly attenuated the increased MDA content but did not affect the nitrite content or SOD activity.These results indicate that genistein pretreatment ameliorates Aβ-induced impairment of shortterm spatial memory in rats through an estrogenic pathway and by inducing attenuation of oxidative stress.

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Section: Methodsmentioning

confidence: 99%

Genistein ameliorates learning and memory deficits in amyloid β(1–40) rat model of Alzheimer’s disease

Bagheri

Joghataei

Mohseni

et al. 2011

Neurobiology of Learning and Memory

209

112

View full text Add to dashboard Cite

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“…The degeneration caused by Aβ in vivo has also been linked to the excessive activation of NMDA receptors [84] . Excitotoxicity resulting from excessive activation of NMDARs may enhance the localized vulnerability of neurons in a manner consistent with AD neuropathology as a consequence of an altered regional distribution of NMDA receptor subtypes.…”

Section: Excitotoxicity In Neurodegenerative Diseasesmentioning

confidence: 99%

Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases

2009

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A pivotal role for excitotoxicity in neurodegenerative diseases is gaining increasingly more acceptance, but the underlying mechanisms through which it participates in neurodegeneration still need further investigation. Excessive activation of glutamate receptors by excitatory amino acids leads to a number of deleterious consequences, including impairment of calcium buffering, generation of free radicals, activation of the mitochondrial permeability transition and secondary excitotoxicity. Recent studies implicate excitotoxicity in a variety of neuropathological conditions, suggesting that neurodegenerative diseases with distinct genetic etiologies may share excitotoxicity as a common pathogenic pathway. Thus, understanding the pathways involved in excitotoxicity is of critical importance for the future clinical treatment of many neurodegenerative diseases. This review discusses the current understanding of excitotoxic mechanisms and how they are involved in the pathogenesis of neurodegenerative diseases.

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“…149 Glutamatergic hyperactivity may be of particular relevance to AD due to a specific role of a beta-amyloid in the regulation of astrocytic glutamate clearance mechanisms. 150,151 To the extent that this process underlies neurodegeneration in other disorders, memantine may prove effective as well.…”

Section: Alzheimer Diseasementioning

confidence: 99%

Glutamate as a therapeutic target in psychiatric disorders

2004

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Glutamate is the primary excitatory neurotransmitter in the mammalian brain. Glutamatergic neurotransmission may be modulated at multiple levels, only a minority of which are currently being exploited for pharmaceutical development. Ionotropic receptors for glutamate are divided into N-methyl-D-aspartate receptor (NMDAR) and AMPA receptor subtypes. NMDAR have been implicated in the pathophysiology of schizophrenia. The glycine modulatory site of the NMDAR is currently a favored therapeutic target, with several modulatory agents currently undergoing clinical development. Of these, the full agonists glycine and D-serine have both shown to induce significant, large effect size reductions in persistent negative and cognitive symptoms when added to traditional or newer atypical antipsychotics in double-blind, placebo-controlled clinical studies. Glycine (GLYT1) and small neutral amino-acid (SNAT) transporters, which regulate glycine levels, represent additional targets for drug development, and may represent a site of action of clozapine. Brain transporters for D-serine have recently been described. Metabotropic glutamate receptors are positively (Group I) or negatively (Groups II and III) coupled to glutamatergic neurotransmission. Metabotropic modulators are currently under preclinical development for neuropsychiatric conditions, including schizophrenia, depression and anxiety disorders. Other conditions for which glutamate modulators may prove effective include stroke, epilepsy, Alzheimer disease and PTSD. Glutamate is the primary excitatory neurotransmitter in the mammalian brain. Approximately 60% of neurons in the brain, including all cortical pyramidal neurons and thalamic relay neurons, utilize glutamate as their primary neurotransmitter. 1 As a result, virtually all thalamocortical, corticocortical and corticofugal neurotransmission in the brain is mediated by glutamate. Glutamate is released from presynaptic terminals in response to neuronal depolarization, and is recycled by excitatory amino acid (EAA) transporters located on both neurons and glia. 2 Within glia, glutamate is converted to glutamine and released into extracellular fluid from which it is reabsorbed into presynaptic terminals and converted back to glutamate via action of neuronal glutaminase. Up to 2/3 of brain energy metabolism is related to reuptake and recycling of glutamate. 3 As such, functional imaging modalities, such as PET and fMRI, indexing activity primarily of brain glutamatergic systems. 4 The exchange of glutamine from glia to neurons is accomplished by coordinated actions of two transport systems, systems N and A, both of which are members of sodium-dependent neutral amino acid (SNAT) family of transporters. 5 These transport systems also transport precursors for cysteine and glycine, which are precursors to glutathione synthesis. 6 As these transporters are electrogenic, glutamate transporters may also participate in cellular signaling. 7 As with glutamate and GABA transporters, these recycling systems may constitute interesti...

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

Cited by 259 publications

References 53 publications

Genistein ameliorates learning and memory deficits in amyloid β(1–40) rat model of Alzheimer’s disease

Genistein ameliorates learning and memory deficits in amyloid β(1–40) rat model of Alzheimer’s disease

Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases

Glutamate as a therapeutic target in psychiatric disorders

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