Assessment of synaptic loss in mouse models of β-amyloid and tau pathology using [18F]UCB-H PET imaging

Vogler, Letizia; Ballweg, Anna; Bohr, Bernd; Briel, Nils; Wind, Karin; Antons, Melissa; Kunze, Lea; Gnörich, Johannes; Lindner, Simon; Gildehaus, Franz-Josef; Baumann, Karlheinz; Bartenstein, Peter; Boening, Guido; Ziegler, Sibylle; Levin, Johannes; Zwergal, Andreas; Höglinger, Günter U.; Herms, Jochen; Brendel, Matthias

doi:10.1016/j.nicl.2023.103484

Cited by 2 publications

(1 citation statement)

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“… 6 In some neurodegenerative and psychiatric disorders, SV2A was reduced 7 , 8 and SV2A loss was related to low synaptic density and brain atrophy. 9 , 10 Our previous study also observed a significant reduction in SV2A levels and hippocampal neuronal damage in PRE rats. 11 Moreover, SV2A overexpression suppressed epileptic seizures and discharges in PRE.…”

Section: Introductionmentioning

confidence: 71%

Synaptic vesicle protein 2A mitigates parthanatos via apoptosis‐inducing factor in a rat model of pharmacoresistant epilepsy

Li,

Wang,

Ren

et al. 2024

CNS Neurosci Ther

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AimsSynaptic vesicle protein 2A (SV2A) is a unique therapeutic target for pharmacoresistant epilepsy (PRE). As seizure‐induced neuronal programmed death, parthanatos was rarely reported in PRE. Apoptosis‐inducing factor (AIF), which has been implicated in parthanatos, shares a common cytoprotective function with SV2A. We aimed to investigate whether parthanatos participates in PRE and is mitigated by SV2A via AIF.MethodsAn intraperitoneal injection of lithium chloride‐pilocarpine was used to establish an epileptic rat model, and phenytoin and phenobarbital sodium were utilized to select PRE and pharmacosensitive rats. The expression of SV2A was manipulated via lentivirus delivery into the hippocampus. Video surveillance was used to assess epileptic ethology. Biochemical tests were employed to test hippocampal tissues following a successful SV2A infection. Molecular dynamic calculations were used to simulate the interaction between SV2A and AIF.ResultsParthanatos core index, PARP1, PAR, nuclear AIF and MIF, γ‐H2AX, and TUNEL staining were all increased in PRE. SV2A is bound to AIF to form a stable complex, successfully inhibiting AIF and MIF nuclear translocation and parthanatos and consequently mitigating spontaneous recurrent seizures in PRE. Moreover, parthanatos deteriorated after the SV2A reduction.SignificanceSV2A protected hippocampal neurons and mitigated epileptic seizures by inhibiting parthanatos via binding to AIF in PRE.

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