TY  - JOUR
A1  - Smilovic, Dinko
A1  - Rietsche, Michael
A1  - Drakew, Alexander
A1  - Vuksic, Mario
A1  - Deller, Thomas
T1  - Constitutive tumor necrosis factor (TNF)-deficiency causes a reduction in spine density in mouse dentate granule cells accompanied by homeostatic adaptations of spine head size
T2  - The journal of comparative neurology
N2  - The majority of excitatory synapses terminating on cortical neurons are found on dendritic spines. The geometry of spines, in particular the size of the spine head, tightly correlates with the strength of the excitatory synapse formed with the spine. Under conditions of synaptic plasticity, spine geometry may change, reflecting functional adaptations. Since the cytokine tumor necrosis factor (TNF) has been shown to influence synaptic transmission as well as Hebbian and homeostatic forms of synaptic plasticity, we speculated that TNF-deficiency may cause concomitant structural changes at the level of dendritic spines. To address this question, we analyzed spine density and spine head area of Alexa568-filled granule cells in the dentate gyrus of adult C57BL/6J and TNF-deficient (TNF-KO) mice. Tissue sections were double-stained for the actin-modulating and plasticity-related protein synaptopodin (SP), a molecular marker for strong and stable spines. Dendritic segments of TNF-deficient granule cells exhibited ∼20% fewer spines in the outer molecular layer of the dentate gyrus compared to controls, indicating a reduced afferent innervation. Of note, these segments also had larger spines containing larger SP-clusters. This pattern of changes is strikingly similar to the one seen after denervation-associated spine loss following experimental entorhinal denervation of granule cells: Denervated granule cells increase the SP-content and strength of their remaining spines to homeostatically compensate for those that were lost. Our data suggest a similar compensatory mechanism in TNF-deficient granule cells in response to a reduction in their afferent innervation.
KW  - dentate gyrus
KW  - homeostatic plasticity
KW  - spine head
KW  - synaptic plasticity
KW  - synaptopodin
KW  - tumor necrosis factor
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/64087
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-640876
SN  - 1096-9861
N1  - Early View: Online Version before inclusion in an issue
N1  - This work was supported by the bilateral Croatian-German project (Ministry of Science and Education of the Republic of Croatia and Deutscher Akademischer Austauschdienst (MZOŠ-DAAD) to M.V. and T.D.), Deutsche Forschungsgemeinschaft (DFG CRC 1080 to T.D.), the Scientific Centre of Excellence for Basic, Clinical and Translation Neuroscience (project “Experimental and clinical research of hypoxic-ischemic damage in perinatal and adult brain“; GA KK01.1.1.01.007 funded by the European Union through the European Regional Development Fund), Europass Mobility grant (to D.S.) and Dr. Senckenbergische Stiftung (to T.D.)
VL  - 2021
IS  - online version before inclusion in an issue
SP  - 1
EP  - 14
PB  - Wiley-Liss
CY  - New York, NY [u.a.]
ER  -