A dose-dependent increase of Tau immunostaining is produced by glutamate toxicity in primary neuronal cultures

Sindou, Philippe; Couratier, Philippe; Barthe, D; Hugon, Jacques

doi:10.1016/0006-8993(92)90476-p

Cited by 42 publications

(12 citation statements)

References 15 publications

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“…Human neurons in culture, when exposed to excitatory amino acids, have been reported to form paired helical filaments, some of which are ultrastructurally identical to the paired helical filaments that are the principal components of NFTs [53]. Along similar lines, a dosedependent increase of tau immunostaining was produced by glutamate toxicity in rat primary neuronal cultures [54]. It is possible that degeneration of the excitatory presynaptic terminal, whatever its cause, is [55] may be another factor leading to progressively increased vulnerability oi" AD neurons.…”

Section: Discussionmentioning

confidence: 85%

Neuronal activity and early neurofibrillary tangles in Alzheimer's disease

Hatanpaa

Brady

Stoll

et al. 1996

Annals of Neurology

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We studied neuronal activity and its relation to the accumulation of neurofibrillary tangles in Alzheimer's disease (AD) neurons by in situ hybridization to cytochrome oxidase subunit III messenger RNA, a marker of mitochondrial energy metabolism. In AD midtemporal cortex, levels of cytochrome oxidase subunit III messenger RNA were decreased by 26% in neurons bearing early-stage neurofibrillary tangles as compared to tangle-free neurons (p < 0.01). However, levels of 12S ribosomal RNA, also encoded by mitochondrial DNA, and of total messenger RNA were decreased only in later stages of tangle development. Comparing tangle-free neurons of 4 AD brains to tangle-free neurons of 3 control brains, levels of cytochrome oxidase subunit III messenger RNA were found to be 25% lower (p < 0.001) in AD tangle-free neurons. Because energy metabolic needs of neurons are mainly determined by synaptic input, the observed decreases in cytochrome oxidase subunit III messenger RNA likely reflect downregulation due to impaired synaptic function in AD. Thus, a failure in synaptic transmission may precede tangle formation. A further decline in neuronal activity is seen as tangle formation progresses. However, these results can also be viewed as showing the viability and continuing activity, albeit at a lower level, of neurons in the early stages of neurofibrillary pathology.

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Section: Discussionmentioning

confidence: 85%

Neuronal activity and early neurofibrillary tangles in Alzheimer's disease

Hatanpaa

Brady

Stoll

et al. 1996

Annals of Neurology

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“…The abrogation of CM- mediated neurotoxicity by MK-801, which also inhibits the increase in Tau expression, suggests that both Tau induction and neuronal death are due to NMDA receptor-mediated excitotoxicity. Previous studies have found that upregulation of Tau following excitotoxic insult can be blocked by MK801 and other NMDA receptor antagonists [54–57]. Furthermore, lowering Tau levels can protect against excitotoxicity, suggesting that excitotoxic neuronal loss requires Tau upregulation [58, 59].…”

Section: Discussionmentioning

confidence: 99%

Elevated MeCP2 in Mice Causes Neurodegeneration Involving Tau Dysregulation and Excitotoxicity: Implications for the Understanding and Treatment of MeCP2 Triplication Syndrome

et al. 2018

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Expression of MeCP2 must be carefully regulated as a reduction or increase results in serious neurological disorders. We are studying transgenic mice in which the MeCP2 gene is expressed at about three times higher than the normal level. Male MeCP2-Tg mice, but not female mice, suffer motor and cognitive deficits and die at 18-20 weeks of age. MeCP2-Tg mice display elevated GFAP and Tau expression within the hippocampus and cortex followed by neuronal loss in these brain regions. Loss of Purkinje neurons, but not of granule neurons in the cerebellar cortex is also seen. Exposure of cultured cortical neurons to either conditioned medium from astrocytes (ACM) derived from male MeCP2-Tg mice or normal astrocytes in which MeCP2 is expressed at elevated levels promotes their death. Interestingly, ACM from male, but not female MeCP2-Tg mice, displays this neurotoxicity reflecting the gender selectivity of neurological symptoms in mice. Male ACM, but not female ACM, contains highly elevated levels of glutamate, and its neurotoxicity can be prevented by MK-801, indicating that it is caused by excitotoxicity. Based on the close phenotypic resemblance of MeCP2-Tg mice to patients with MECP2 triplication syndrome, we suggest for the first time that the human syndrome is a neurodegenerative disorder resulting from astrocyte dysfunction that leads to Tau-mediated excitotoxic neurodegeneration. Loss of cortical and hippocampal neurons may explain the mental retardation and epilepsy in patients, whereas ataxia likely results from the loss of Purkinje neurons.

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“…The excess activation of neuronal glutamate receptors causing cell death via increased cellular calcium may be one mechanism involved in motor neuron disease. Glutamate can also produce neuronal degeneration by increasing tau mRNA expression and phosphorylated Tau protein, as observed in neuronal cultures (211–214). Decrease of glutamate transport may provoke elevated synaptic glutamate concentration.…”

Section: Excitotoxicity Genesmentioning

confidence: 99%

Genetic epidemiology of amyotrophic lateral sclerosis

2003

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Amyotrophic lateral sclerosis (ALS) is a late onset, rapidly progressive and ultimately fatal neurological disorder, caused by the loss of motor neurons in the brain and spinal cord. Familial aggregation of ALS, with an age-dependent but high penetrance, is a major risk factor for ALS. Familial ALS (FALS) is clinically and genetically heterogeneous. Three genes and linkage to four additional gene loci have been identified so far and may either predominantly lead to ALS (ALSI-ALS6) or cause multisystem neurodegeneration with ALS as an occasional symptom (tauopathies, ALS-dementia complex). This review presents a tentative classification of the "major" ALS genes and ALS "susceptibility" genes, that may act as susceptibility factors for neurodegeneration in interaction with other genetic or environmental risk factors. Considering that mutations in ALS genes explain approximately 10% of familial as well as sporadic ALS, and most remaining cases of the discase are thought to result form the interaction of several genes and environmental factors, ALS is a paradigm for multifactorial discases.

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A dose-dependent increase of Tau immunostaining is produced by glutamate toxicity in primary neuronal cultures

Cited by 42 publications

References 15 publications

Neuronal activity and early neurofibrillary tangles in Alzheimer's disease

Neuronal activity and early neurofibrillary tangles in Alzheimer's disease

Elevated MeCP2 in Mice Causes Neurodegeneration Involving Tau Dysregulation and Excitotoxicity: Implications for the Understanding and Treatment of MeCP2 Triplication Syndrome

Genetic epidemiology of amyotrophic lateral sclerosis

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