Zinc chelation during non-lesioning overexcitation results in neuronal death in the mouse hippocampus

Domínguez, M.I.; Blasco-Ibáñez, José Miguel; Crespo, Carlos; Marqués-Marí, Ana Isabel; Martı́nez-Guijarro, Francisco José

doi:10.1016/s0306-4522(02)00731-5

Cited by 50 publications

(47 citation statements)

References 89 publications

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“…This dose is not enough to induce cell death (32-40 mg/kg would be necessary), but it is high enough to induce strong over excitation in the granular cells as seen by Fos proteins and Heat Shock Proteins (Domínguez et al, 2003b(Domínguez et al, , 2006. No differences were observed in the expression of calretinin by granule cells respective to controls, indicating that the effects on granule cells maturation observed in the pilocarpine model are not due to the over excitation induced by its administration.…”

Section: The Lesion Induced By Pilocarpine In the Mousementioning

confidence: 97%

“…This dose is not enough to produce excitotoxic damage in the brain but induces transient overexcitation in the hippocampus inducing Fos proteins and Heat Shock Proteins (Domínguez et al, 2003b(Domínguez et al, , 2006. Four animals were killed 2 days after kainic administration and the other four after 7 days.…”

Section: Hippocampal Overexcitation Using Kainic Acidmentioning

confidence: 99%

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Loss of input from the mossy cells blocks maturation of newly generated granule cells

et al. 2007

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The objective of this work is to check whether the input from the mossy cells to the inner molecular layer is necessary for the integration and maturation of the newly generated granule cells of the dentate gyrus (DG) in mice, and if after status epilepticus the sprouting of the mossy fibers can substitute for this projection. Newly generated cells were labeled by administration of 5-bromo-deoxyuridine either before or after pilocarpine administration. The neuronal loss in the hippocampus after administration of pilocarpine combined with scopolamine and diazepam seemed restricted to the hilar mossy cells. The maturation of the granule cells was studied using immunohistochemistry for calretinin and NeuN in combination with detection of 5-bromo-deoxyuridine. The sprouting of the mossy fibers was detected using Timm staining for zinc-rich boutons. In normal conditions, granule cells took about 2 weeks to lose the immature marker calretinin. After the loss of the mossy cells, newly generated granule cells remained expressing calretinin for more than a month, until the sprouting of the mossy fibers substituted for the projection of the mossy cells in the inner molecular layer of the DG. Therefore, a proper pattern of connectivity is necessary for the normal development and integration of newly generated granule cells in the adult brain. In a changed environment they cannot adapt transforming in other cell types; simply they are unable to mature. The sprouting of the mossy fibers, although aberrant and a probable source of epileptic activity, may be important for the correct physiology of the granule cells, restoring a likeness of normality in their connective environment. The survival of granule cells incorporated as mature neurons was increased after pilocarpine when compared with normal conditions. Thus, it is likely that the reorganization of the circuitry after the loss of the mossy cells facilitates the survival and incorporation of the newly generated granule cells.

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Section: The Lesion Induced By Pilocarpine In the Mousementioning

confidence: 97%

Section: Hippocampal Overexcitation Using Kainic Acidmentioning

confidence: 99%

Loss of input from the mossy cells blocks maturation of newly generated granule cells

et al. 2007

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“…Due to its membrane-permeant nature, DEDTC may moreover have influenced intracellular signaling cascades or metal-dependent enzymes. However, it has been suggested that Zn 2+ is more easily chelated by DEDTC after being released into the extracellular space [71] so that the low dose regimen used in the present study should have minimized unspecific effects, like abstraction of Zn 2+ from metalloproteins or intracellular stores.…”

Section: Limitations and Relevance Of The Present Workmentioning

confidence: 98%

Diethyldithiocarbamate-mediated zinc ion chelation reveals role of Cav2.3 channels in glucagon secretion

Drobinskaya

Neumaier

Pereverzev

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Peptide-hormone secretion is partially triggered by Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) and gene inactivation of Zn2+-sensitive Cav2.3-type VGCCs is associated with disturbed glucose homeostasis in mice. Zn2+ has been implicated in pancreatic islet cell crosstalk and recent findings indicate that sudden cessation of Zn2+ supply during hypoglycemia triggers glucagon secretion in rodents. Here we show that diethyldithiocarbamate (DEDTC), a chelating agent for Zn2+ and other group IIB metal ions, differentially affects blood glucose and serum peptide hormone level in wild-type mice and mice lacking the Cav2.3-subunit. Fasting glucose and glucagon level were significantly higher in Cav2.3-deficient compared to wild-type mice, while DEDTC Zn2+-chelation produced a significant and correlated increase of blood glucose and serum glucagon concentration in wild-type but not Cav2.3-deficient mice. Glucose tolerance tests revealed severe glucose intolerance in Zn2+-depleted Cav2.3-deficient but not vehicle-treated Cav2.3-deficient or Zn2+-depleted wildtype mice. Collectively, these findings indicate that Cav2.3 channels are critically involved in the Zn2+-mediated suppression of glucagon secretion during hyperglycemia. Especially under conditions of Zn2+ deficiency, ablation or dysfunction of Cav2.3 channels may lead to severe disturbances in glucose homeostasis.

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“…[26][27][28][29] When DEDTC was applied to the bovine retina, the b-wave amplitude starts to decrease within 15-20 min of superfusion ( Figure 5A). The initial b-wave amplitude was 54.8 ± 0.8 µV (n = 5), and decreased significantly (p < 0.01) to 42.7 ± 1.3 µV (n = 3) by adding DEDTC (30 µM), and consecutively to 31.2 ± 2.0 µV (n = 5) by adding 100 µM DEDTC.…”

Section: Effect Of Dedtc On Retinal Signalling Recorded As Changes Imentioning

confidence: 99%

Effect of ZnCl₂and Chelation of Zinc Ions by N,N-Diethyldithiocarbamate (DEDTC) on the ERG b-Wave Amplitude from the Isolated Superfused Vertebrate Retina

Siapich

Wrubel

Albanna

et al. 2010

Current Eye Research

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Zinc chelation during non-lesioning overexcitation results in neuronal death in the mouse hippocampus

Cited by 50 publications

References 89 publications

Loss of input from the mossy cells blocks maturation of newly generated granule cells

Loss of input from the mossy cells blocks maturation of newly generated granule cells

Diethyldithiocarbamate-mediated zinc ion chelation reveals role of Cav2.3 channels in glucagon secretion

Effect of ZnCl₂and Chelation of Zinc Ions by N,N-Diethyldithiocarbamate (DEDTC) on the ERG b-Wave Amplitude from the Isolated Superfused Vertebrate Retina

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Zinc chelation during non-lesioning overexcitation results in neuronal death in the mouse hippocampus

Cited by 50 publications

References 89 publications

Loss of input from the mossy cells blocks maturation of newly generated granule cells

Loss of input from the mossy cells blocks maturation of newly generated granule cells

Diethyldithiocarbamate-mediated zinc ion chelation reveals role of Cav2.3 channels in glucagon secretion

Effect of ZnCl2and Chelation of Zinc Ions by N,N-Diethyldithiocarbamate (DEDTC) on the ERG b-Wave Amplitude from the Isolated Superfused Vertebrate Retina

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Effect of ZnCl₂and Chelation of Zinc Ions by N,N-Diethyldithiocarbamate (DEDTC) on the ERG b-Wave Amplitude from the Isolated Superfused Vertebrate Retina