3-Nitropropionic Acid Neurotoxicity in Hippocampal Slice Cultures: Developmental and Regional Vulnerability and Dependency on Glucose

Noer, Helle; Kristensen, Bjarne Winther; Noraberg, Jens; Zimmer, Jens; Gramsbergen, Jan Bert

doi:10.1006/exnr.2002.7934

Cited by 15 publications

(16 citation statements)

References 66 publications

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“…Gradual neurodegeneration was evident across the 3-NP exposure period, with damage eventually being expressed in the three major hippocampal subfields. Others have reported CA1 selectivity for 3-NP-mediated damage in hippocampal slice cultures prepared from younger animals (Noer et al, 2002). Note that our protective results with memantine correspond with several studies using longterm slice cultures to describe the innate vulnerability of the hippocampus to over-activation of glutamate receptors including NMDA receptors (Bahr et al, 1995b;Bruce et al, 1995;Newell et al, 1997;Kristensen et al, 2001;Bonde et al, 2005).…”

Section: Treatment Days Controlsupporting

confidence: 89%

3-Nitropropionic acid toxicity in hippocampus: Protection throughN-methyl-D-aspartate receptor antagonism

et al. 2006

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The over-activation of glutamate receptors can lead to excitotoxic cell death and is believed to be involved in the progression of neurodegenerative events in the vulnerable hippocampus. Here, we used an in vitro slice model to study toxicity produced in the hippocampus by the mitochondrial toxin 3-nitropropionic acid (3-NP). The organotypic slice cultures exhibit native cellular organization as well as dense arborization of neuronal processes and synaptic contacts. The hippocampal slices were exposed to 3-NP for 2-20 days, causing calpain-mediated breakdown of the spectrin cytoskeleton, a loss of pre- and postsynaptic markers, and neuronal atrophy. The N-methyl-D-aspartate (NMDA) receptor antagonist memantine reduced both the cytoskeletal damage and synaptic decline in a dose-dependent manner. 3-NP-induced cytotoxicity, as determined by the release of lactate dehydrogenase, was also reduced by memantine with EC50 values from 1.7 to 2.3 microM. Propidium iodide fluorescence and phase contrast microscopy confirmed memantine neuroprotection against the chronic toxin exposure. In addition, the protected tissue exhibited normal neuronal morphology in the major hippocampal subfields. These results indicate that antagonists of NMDA-type glutamate receptors are protective during the toxic outcome associated with mitochondrial dysfunction. They also provide further evidence of memantine's therapeutic potential against neurodegenerative diseases.

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Section: Treatment Days Controlsupporting

confidence: 89%

3-Nitropropionic acid toxicity in hippocampus: Protection throughN-methyl-D-aspartate receptor antagonism

et al. 2006

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“…The LDH activity was found to be increased after 3-NP administration. The loss of intracellular LDH and its release into the culture medium is an indicator of cell death due to cell membrane damage induced by 3-NP [50]. Naringin decreased the LDH release and indicates its protective effect through the maintenance of plasma membrane integrity.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells

Gopinath

Sudhandiran

2015

Mol Cell Biochem

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“…Here we present the use of organotypic hippocampal slice cultures as in vitro models for stroke [1][2][3][4][5][6][7], including glutamate receptor mediated excitotoxic lesions [8][9][10][11][12], epilepsia [13][14][15][16], and Alzheimer's disease (AD) [17][18][19][20][21][22][23], as well as studies on neuroprotection [1,6,24] and repair mechanisms [25,26]. Also studies on non-excitotoxic neurotoxic compounds are included [27][28][29][30][31][32], as well as the experimental use of slice cultures in the studies of HIV neurotoxicity [33,34] and traumatic brain injury (TBI) [35,36].…”

Section: Short History Of Disease Models Methods and Type Of Donor Smentioning

confidence: 99%

Organotypic Hippocampal Slice Cultures for Studies of Brain Damage, Neuroprotection and Neurorepair

Poulsen²,

et al. 2005

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Slices of developing brain tissue can be grown for several weeks as so-called organotypic slice cultures. Here we summarize and review studies using hippocampal slice cultures to investigate mechanisms and treatment strategies for the neurodegenerative disorders like stroke (cerebral ischemia), Alzheimer's disease (AD) and epilepsia. Studies of non-excitotoxic neurotoxic compounds and the experimental use of slice cultures in studies of HIV neurotoxicity, traumatic brain injury (TBI) and neurogenesis are included. For cerebral ischemia, experimental models with oxygen-glucose deprivation (OGD) and exposure to glutamate receptor agonists (excitotoxins) are reviewed. For epilepsia, focus is on induction of seizures with effects on neuronal loss, axonal sprouting and neurogenesis. For Alzheimer's disease, the review centers on the use of beta-amyloid (Abeta) in different models, while the section on repair is focused on neurogenesis and cell migration. The culturing techniques, set-up of models, and analytical tools, including markers for neurodegeneration, like the fluorescent dye propidium iodide (PI), are reviewed and discussed. Comparisons are made between hippocampal slice cultures and other in vitro models using dispersed cell cultures, experimental in vivo models, and in some instances, clinical trials. New techniques including slice culturing of hippocampal tissue from transgenic mice as well as more mature brain tissue, and slice cultures coupled to microelectrode arrays (MEAs), on-line biosensor monitoring, and time-lapse fluorescence microscopy are also presented.

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3-Nitropropionic Acid Neurotoxicity in Hippocampal Slice Cultures: Developmental and Regional Vulnerability and Dependency on Glucose

Cited by 15 publications

References 66 publications

3-Nitropropionic acid toxicity in hippocampus: Protection throughN-methyl-D-aspartate receptor antagonism

3-Nitropropionic acid toxicity in hippocampus: Protection throughN-methyl-D-aspartate receptor antagonism

Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells

Organotypic Hippocampal Slice Cultures for Studies of Brain Damage, Neuroprotection and Neurorepair

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