2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
June 2nd, 2025
Version: 1
Department of Biomedicine Aarhus University, Denmark
neuroscience
biorxiv

Lack of functional STING modulates immunity but does not protect dopaminergic neurons in the alpha-synuclein preformed fibrils Parkinson's Disease mouse model

Klaestrup, I. H.Open in Google Scholar•Reinert, L. S.Open in Google Scholar•Ferreira, S. A.Open in Google Scholar•Lauritsen, J.Open in Google Scholar•Toft, G. U.Open in Google Scholar•Gram, H.Open in Google Scholar•Jensen, P. H.Open in Google Scholar•Paludan, S. R.Open in Google Scholar•Romero-Ramos, M.Open in Google Scholar

Microglia response is proposed to be relevant in the neurogenerative process associated with alpha-synuclein (a-syn) pathology in Parkinson\'s disease (PD). STING is a protein related to the immune sensing of DNA and autophagy, and it has been proposed to be involved in PD neurodegeneration. To investigate this, we injected 10 g of murine pre-formed fibrils (PFFs) of a-syn (or monomeric and PBS as controls) into the striatum of wild-type (WT) and STINGgt/gt mice, which lack functional STING. We examined motor behavior and brain pathology at 1- and 6-months post-injection. STINGgt/gt mice showed more motor changes associated with PFF injection than WT mice. STINGgt/gt mice had a differential immune response to PFF with early and sustained increased microglia numbers and earlier macrophagic CD68 response, but milder changes in the expression of immune-relevant markers such as TLR2, TLR4, IL1b, and TREM2. However, the lack of STING did not induce changes in the extent of a-syn pathology nor the p62 accumulation seen in the model. Altogether, this resulted in a faster but similar degree of nigrostriatal dopaminergic degeneration after 6 months. Therefore, the data do not support a necessary role for STING in the a-syn induced nigral neuronal loss in the PFF-PD mouse model used here. However, the results suggest a functional relevance for STING in the brain response to the excess of amylogenic proteins such as a-syn that can contribute to symptomatic changes.

Similar Papers

biorxiv
Wed Jun 04 2025
Towards Unified Neural Decoding with Brain Functional Network Modeling
Recent achievements in implantable brain-computer interfaces (iBCIs) have demonstrated the potential to decode cognitive and motor behaviors with intracranial brain recordings; however, individual physiological and electrode implantation heterogeneities have constrained current approaches to neural decoding within single individuals, rendering interindividual neural decoding elusive. Here, we pres...
Wu, D.
•
Bu, L.
•
Jia, Y.
•
Cao, L.
...•
Mohamad, S.
biorxiv
Wed Jun 04 2025
Dendritic computation for rule-based flexible categorization
A hallmark of intelligent behavior is the ability to flexibly respond to external sensory inputs based on dynamically changing rules. A central question is how neurons in the brain implement computations underlying intelligent behaviors. The neocortical pyramidal neurons use their elaborated dendritic arbors to segregate a plethora of inputs and dynamically integrate them--a process known as dendr...
Xu, N.-l.
•
Zhang, Y.
•
Hu, Y.
•
Zhang, Z.
...•
Schiller, J.
biorxiv
Wed Jun 04 2025
OPM quantum sensors enhance non-invasive neuroimaging performance
Much of our understanding of how neural circuit activity relates to human behaviour as well as mental health, stems from non-invasive assessments of the central nervous system. Further progress in key questions, however, requires a higher differentiation of circuit-level activity, which remains constrained by the sensitivity and resolution of existing instruments. Here we show that neural quantum ...
Brickwedde, M.
•
Anders, P.
•
Krueger, P.
•
Sander, T.
•
Uhlhaas, P.
biorxiv
Wed Jun 04 2025
Revealing synaptic nanostructure distribution through automatic dendritic spine segmentation and single-molecule localization microscopy
Relating dendritic spine morphology to synaptic organization in brain tissue is essential for understanding excitatory synaptic transmission and plasticity. Single-molecule localization microscopy (SMLM) offers the spatial precision needed to study the synaptic protein distribution at the nanoscale. However, the widefield setup required for SMLM produces diffraction-limited images with poor contra...
Zhang, J.
•
Vaidya, R. M.
•
Pendharkar, R.
•
Chung, H. J.
•
Selvin, P. R.
biorxiv
Wed Jun 04 2025
Two Sites, Two Languages: Dual-site tDCS and EEG Evidence for L1 Feature Transfer in L2
The neural bases of syntactic and semantic processing remain unclear. While prior transcranial direct current stimulation (tDCS) studies have targeted either the inferior frontal gyrus (LIFG) or left superior temporal gyrus (LSTG), we test whether dual stimulation of both alters second language (L2) anomaly based on native language (L1). Chinese and Korean participants evaluated Japanese sentence ...
Salem, A. M.
•
Gallagher, D.
•
Yamada, E.
•
Ohta, S.
biorxiv
Wed Jun 04 2025
Focused ultrasound neuromodulation of mediodorsal thalamus disrupts decision flexibility during reward learning
When learning to find the most beneficial course of action, the prefrontal cortex guides decisions by comparing estimates of the relative value of the options available. Basic neuroscience studies in animals support the view that the thalamus can regulate the activity within and across the prefrontal cortex. However, it is unknown if it can modify value-based decision making in humans. Understandi...
Mackenzie, G.
•
Gilmour, W.
•
Yang, S. S.
•
Suveges, S.
...•
Gilbertson, T.
biorxiv
Wed Jun 04 2025
Valence of sensory stimulation as a key feature for subcortical entrainment: Insights from human intracranial EEG
Sensory rhythmic stimulation enhances executive functions by entraining oscillations in higher-order cortical networks, but its effects on subcortical structures remain unclear. We propose that stimulus valence is a key feature to enable subcortical entrainment. Using intracranial EEG in epileptic patients, we first show that visual search is supported by cortico-subcortical theta (5Hz) activity. ...
Hoyer, R. S.
•
Bernier, M.-F.
•
Martineau, L.
•
Lessard Bonaventure, P.
...•
Albouy, P.
biorxiv
Wed Jun 04 2025
A Unique Role for the Hippocampus in Cue Integration During Human Spatial Navigation
A central question in cognitive neuroscience is how the brain integrates distinct sensory and perceptual inputs to improve cognitive performance. This study investigated this question in the context of human spatial navigation by combining high-field 3T fMRI and desktop virtual reality. Participants encoded and retrieved spatial locations using either landmarks alone (landmark condition), visual s...
Wei, Z.
•
Wolbers, T.
•
Chen, X.
biorxiv
Wed Jun 04 2025
Thermal cycling-hyperthermia attenuates rotenone-induced cell injury in SH-SY5Y cells through heat-activated mechanisms
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. It is characterized by mitochondrial dysfunction, increased reactive oxygen species (ROS), -synuclein (-syn) and phosphorylated-tau protein (p-tau) aggregation, and dopamin-ergic neuron cell death. Current drug therapies only provide temporary symptomatic relief and fail to stop or reverse disease progression due to t...
Kuo, Y.-Y.
•
Lin, G.-B.
•
Chen, Y.-M.
•
Liu, H.-H.
...•
Chao, C.-Y.
biorxiv
Wed Jun 04 2025
Memory by a thousand rules: Automated discovery of multi-type plasticity rules reveals variety and degeneracy at the heart of learning.
Synaptic plasticity is widely understood to be the basis of learning and memory, but the link between synaptic changes and network properties remains elusive. Here, we use automated search algorithms to obtain thousands of excitatory(E)-to-E, E-to-inhibitory(I), IE and II plasticity rules working in cooperation in recurrent spiking networks. We selected these rule quadruplets solely based on their...
Confavreux, B.
•
Harrington, Z.
•
Kania, M.
•
Ramesh, P.
...•
Vogels, T. P.