Seizures and neuronal damage in mice lacking vesicular zinc
- PMID: 10759303
- DOI: 10.1016/s0920-1211(99)00121-7
Seizures and neuronal damage in mice lacking vesicular zinc
Abstract
Synaptically released zinc has neuromodulatory capabilities that could result in either inhibition or enhancement of neuronal excitability. To determine the net effects of vesicular zinc release in the brain in vivo, we examined seizure susceptibility and seizure-related neuronal damage in mice with targeted disruption of the gene encoding the zinc transporter, ZnT3 (ZnT3-/- mice). ZnT3-/- mice, which lack histochemically reactive zinc in synaptic vesicles, had slightly higher thresholds to seizures elicited by the GABA(A) antagonist, bicuculline, and no differences in seizure threshold were seen in response to pentylenetetrazol or flurothyl. However, ZnT3-/- mice were much more susceptible than wild-type mice to limbic seizures elicited by kainic acid, suggesting that the net effect of hippocampal zinc on acute seizures in vivo is inhibitory. The hippocampi of ZnT3-/- mice showed typical seizure-related neuronal damage in response to kainic acid, demonstrating that damage to the targets of zinc-containing neurons can occur independently of synaptically released zinc. Mice lacking the neuronal zinc-binding protein metallothionein III (MT-III) are also more susceptible to kainic acid-induced seizures. Double knockout (ZnT3 and MT3) mice show the same response to kainic acid as ZnT3-/- mice, suggesting that ZnT3 and MT-III function in the same pathway.
Similar articles
-
Accumulation of zinc in degenerating hippocampal neurons of ZnT3-null mice after seizures: evidence against synaptic vesicle origin.J Neurosci. 2000 Jun 1;20(11):RC79. doi: 10.1523/JNEUROSCI.20-11-j0003.2000. J Neurosci. 2000. PMID: 10807937 Free PMC article.
-
Zinc released from metallothionein-iii may contribute to hippocampal CA1 and thalamic neuronal death following acute brain injury.Exp Neurol. 2003 Nov;184(1):337-47. doi: 10.1016/s0014-4886(03)00382-0. Exp Neurol. 2003. PMID: 14637104
-
Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene.Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1716-21. doi: 10.1073/pnas.96.4.1716. Proc Natl Acad Sci U S A. 1999. PMID: 9990090 Free PMC article.
-
Zinc transporter 3 (ZnT3) and vesicular zinc in central nervous system function.Neurosci Biobehav Rev. 2017 Sep;80:329-350. doi: 10.1016/j.neubiorev.2017.06.006. Epub 2017 Jun 15. Neurosci Biobehav Rev. 2017. PMID: 28624432 Review.
-
Zinc-containing neurons.Biol Signals. 1994 May-Jun;3(3):127-39. doi: 10.1159/000109536. Biol Signals. 1994. PMID: 7531563 Review.
Cited by
-
The Zinc-Sensing Receptor GPR39 in Physiology and as a Pharmacological Target.Int J Mol Sci. 2021 Apr 8;22(8):3872. doi: 10.3390/ijms22083872. Int J Mol Sci. 2021. PMID: 33918078 Free PMC article. Review.
-
HB-EGF activates EGFR to induce reactive neural stem cells in the mouse hippocampus after seizures.Life Sci Alliance. 2024 Jul 8;7(9):e202201840. doi: 10.26508/lsa.202201840. Print 2024 Sep. Life Sci Alliance. 2024. PMID: 38977310 Free PMC article.
-
Chemical blocking of zinc ions in CNS increases neuronal damage following traumatic brain injury (TBI) in mice.PLoS One. 2010 Apr 9;5(4):e10131. doi: 10.1371/journal.pone.0010131. PLoS One. 2010. PMID: 20396380 Free PMC article.
-
Shank and Zinc Mediate an AMPA Receptor Subunit Switch in Developing Neurons.Front Mol Neurosci. 2018 Nov 9;11:405. doi: 10.3389/fnmol.2018.00405. eCollection 2018. Front Mol Neurosci. 2018. PMID: 30524232 Free PMC article.
-
Blockade of Ca2+-permeable AMPA/kainate channels decreases oxygen-glucose deprivation-induced Zn2+ accumulation and neuronal loss in hippocampal pyramidal neurons.J Neurosci. 2002 Feb 15;22(4):1273-9. doi: 10.1523/JNEUROSCI.22-04-01273.2002. J Neurosci. 2002. PMID: 11850455 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Molecular Biology Databases