title: Distinct expression and distribution of vesicular proteins in the hippocampus of TNFa-deficient mice during development.
abstract: Tumor necrosis factor alpha (TNFa) is a cytokine produced mainly by cells of the immune system. It is also expressed by brain neurons and glia. In the brain, TNFa governs synaptic plasticity, such as long-term potentiation and learning. Using TNFa-deficient mice (TNFa-KO) and immunohistochemical techniques, we resolved the spatio-temporal effect of TNFa on the expression of vesicular soluble N-ethylmaleimide-sensitive factor attachment protein receptor (v-SNARE) in the presynaptic terminals of the hippocampus during the first month of development. During postnatal days 1-14, the levels of Synaptotagmin I and VAMP II were similar in the hippocampus of TNFa-KO and wild type (wt) mice. However, the levels of Syntaptotagmin II were reduced in the pyramidal cell layer of the CA1 region in TNFa-KO. At postnatal day 21, both proteins accomplished comparable levels in the hippocampus of TNFa-KO and wt mice. In addition, TNFa deficiency impairs the correlation of expression of Synaptotagmin I and II in CA1 region. The expression of those proteins in the CA1 stratum radiatum was uniform during development and similar in both mice groups. Higher expression of all examined proteins was demonstrated in dendritic fields of the CA3 region in TNFa-KO as compared to wt mice. We suggest that the impairment of synaptic plasticity by TNFa may be related to its modulation of synaptic vesicle proteins.
authors.affiliation: Department of Developmental Molecular Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. havag@bgumail.bgu.ac.il
authors.forename: Hava
authors.initials: H
authors.lastname: Golan
authors.forename: Tamar
authors.initials: T
authors.lastname: Levav
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Huleihel
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002135:Calcium-Binding Proteins; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism*; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D050863:Synaptotagmin I; D050861:Synaptotagmin II; D050857:Synaptotagmins; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency*; D033921:Vesicular Transport Proteins
chemical_list: D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D050600:SNARE Proteins; D050863:Synaptotagmin I; D050861:Synaptotagmin II; C494311:Syt1 protein, mouse; C494263:Syt2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D033921:Vesicular Transport Proteins; D050857:Synaptotagmins