title: Synaptic Zn2+and febrile seizure susceptibility.
abstract: Zn2+, the second most prevalent trace element in the body, is essential for supporting a wide range of biological functions. While the majority of Zn2+in the brain is protein-bound, a significant proportion of free Zn2+is found co-localized with glutamate in synaptic vesicles and is released in an activity-dependent manner. Clinical studies have shown Zn2+levels are significantly lower in blood and cerebrospinal fluid of children that suffer febrile seizures. Likewise, investigations in multiple animal models demonstrate that low levels of brain Zn2+increase seizure susceptibility. Recent work provides human genetic evidence that disruption of brain Zn2+homeostasis at the level of the synapse is associated with increased seizure susceptibility. In this review, we have explored the clinical, functional and genetic data supporting the view that low synaptic Zn2+increases cellular excitability and febrile seizure susceptibility. Finally, the review focuses on the potential of therapeutic Zn2+supplementation for at risk patients.
authors: Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
authors: Christopher A
authors: CA
authors: Reid
authors: Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC, Australia.
authors: Michael S
authors: MS
authors: Hildebrand
authors: Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
authors: Saul A
authors: SA
authors: Mullen
authors: Cell Signalling and Cell Death Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
authors: Joanne M
authors: JM
authors: Hildebrand
authors: Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC, Australia.
authors: Samuel F
authors: SF
authors: Berkovic
authors: Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
authors: Steven
authors: S
authors: Petrou
mesh_terms: D000818:Animals; D006801:Humans; D003294:Seizures, Febrile / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: D015032:Zinc