- Open Access
Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity
BMC Neuroscience volume 24, Article number: 14 (2023)
Neuroinflammation plays a critical role in Amyloid-β (Aβ) pathophysiology. The cytokine, interleukin-17A (IL-17) is involved in the learning and memory process in the central nervous system and its level was reported to be increased in Alzheimer's disease (AD) brain, while the effect of IL-17 on the course of Aβ has not been well defined.
Here, we used APP/PS1 mice to detect the IL-17 expression level. Primary hippocampal neurons were treated with IL-17, and immunofluorescence was used to investigate whether IL-17 induced neuron damage. At the same time, male C57BL/6 mice were injected with Aβ42 to mimic the Aβ model. Then IL-17 neutralizing antibody (IL-17Ab) was used to inject into the lateral ventricle, and the Open field test, Novel Objective Recognition test, Fear condition test were used to detect cognitive function. LTP was used to assess synaptic plasticity, molecular biology technology was used to assess the IL-17/TRAF6/NF-κB pathway, and ELISA was used to detect inflammatory factors.
Altogether, we here found that IL-17 was increased in APP/PS1 mice, and it induced neural damage by the administration to primary hippocampal neurons. Interestingly, Using Aβ42 mice, the results showed that the level of IL-17 was increased in Aβ42 model mice, and IL-17Ab could ameliorate Aβ-induced neurotoxicity and cognitive decline in C57BL/6 mice by downregulation the TRAF6/NF-κB pathway.
These findings highlight the pathogenic role of IL-17 in Aβ induced-synaptic dysfunction and cognitive deficits. Inhibition of IL-17 could ameliorate Aβ-induced neurotoxicity and cognitive decline in C57BL/6 mice by downregulation of the TRAF6/NF-κB pathway, which provides new clues for the mechanism of Aβ-induced cognitive impairments, and a basis for therapeutic intervention.
Alzheimer’s disease (AD) is the most common type of dementia and a rising threat to public health [1,2,3,4]. Amyloid beta (Aβ) is a hallmark of Alzheimer's disease, and its accumulation in the brain is thought to play a key role in the molecular pathology of AD [5,6,7], Aβ is thought to have the strongest toxicity to synaptic damage, neuronal death, and cognitive impairments[8, 9]. Neuroinflammation plays a critical role in Aβ pathophysiology [10, 11], but its etiopathogenesis is still unclear. The interleukin 17 (IL-17) family of cytokines contains 6 structurally related cytokines, IL-17A through IL-17F. Although less is known about IL-17B–F, IL-17A (the prototypical member of this family, commonly known as IL-17) has received much attention for its pro-inflammatory role . IL-17 is a pro-inflammatory cytokine produced by various types of cells including CD4 T cells which are categorized as a new subset called Th17 cells, acting on its specific receptor (IL-17R) highly expressed in the CA1 region of the hippocampus [13, 14]. After binding to IL-17, IL-17R could recruit NF-κB activator (ACT1) with the same domain through its SEFIR domain. ACT1 in turn recruits tumour necrosis factor receptor-associated factor 6 (TRAF-6), which is an adapter protein that mediates a wide array of protein–protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. TRAF6 was identified as a mediator of interleukin-1 receptor (IL-1R)-mediated activation of NF-κB, which plays a vital role by regulating certain functions like neuronal plasticity and neuronal growth. [15,16,17]. It is interesting to note that plasma IL-17 level has been identified as one of the plasma biomarkers for AD diagnosis and neocortical Aβ load [18, 19]. In addition to this, it was reported that IL-17 triggers the onset of cognitive and synaptic deficits in the early stages of Alzheimer's disease . We here found that IL-17 was increased in APP/PS1 mice, but the effect of IL-17 on the course of Aβ has been unclear. Therefore, we further wanted to investigate whether IL17 is involved in Aβ neurotoxicity.
In this study, we here found that the level of IL-17 was increased in Aβ42 model mice, and IL-17Ab could ameliorate Aβ-induced neurotoxicity and cognitive decline in C57BL/6 mice by downregulating the TRAF6/ NF-κB pathway, which provides new clues for the mechanism of Aβ-induced cognitive impairments, and a basis for therapeutic intervention.
Materials and methods
All methods were carried out in accordance with relevant ARRIVE guidelines. All methods were approved by the Animal Care Committees of the Ethics Committee of Renmin Hospital, Wuhan University (IACUC Issue No. WDRY2018-K033).
Animals and reagents
Male C57BL/6 mice (2 months old, 20 ± 2 g) were purchased from the Center for Animal Experiment of Wuhan University. 6 months Male APP/PS1 mice (APPswe, PSEN1dE9 and 85Dbo/MmJNju mice) were purchased from Model Animal Research Center of Nanjing University (Nanjing, China). The animals were housed in Experimental Animal Central of Renmin Hospital of Wuhan University under standard laboratory conditions: natural lighting for 12 h then total darkness of another 12 h with water and ad libitum food. Mice were randomly divided into groups and treated as explained in different parts of the study.
Enzyme-linked ImmunoSorbent assays (Elisa)
The hippocampi were lysed in RIPA buffer and centrifuged at 3000 × g for 10 min at 4 °C and the supernatant was collected. Anti-mouse IL-17 Elisa kit from Elabscience Biotechnology (Wuhan, China) was used to assay hippocampus IL-17 level, according to the manufacturer’s instructions.
Primary hippocampal neuron Culture
Primary hippocampal neurons were dissected from the brains of E18 C57BL/6 mice embryos according to previously described procedures with minor modifications [21, 22]. Neurons were cultured in 12-well plates coated with 100 μg/mL poly-D-lysine and supplemented with 2% (v/v) B-27 and 1 × GlutaMAX. The neurons cultured for 9 days were used in experiments. In the experiment, the cells were divided into different groups: control group, IL-17 group (recombinant IL-17, 10 ng/mL, R&D Systems, Cat# 421-M). After treatments, cells were collected and lysed in RIPA buffer for further biological detection or fixed with 4% paraformaldehyde for immunofluorescence imaging. All cell culture reagents were purchased from Thermo Fisher Scientific.
The intracerebroventricular surgery was performed as follows: anterior–posterior: −0.3 mm; mediolateral: -1 mm; dorsoventral: −2.3 mm (from bregma and dura, flat skull). After injection, the needle was kept in place for 10 min to avoid solution flowback.
Aβ42 (Qiangyao Biotechnology) was oligomerized according to the procedure described previously [23, 24]. In brief, the Aβ42 was dissolved in 1% (vol/vol) DMSO and diluted in physiological saline to a final concentration of 2.0 μg/μL. Then, the solution was incubated at 37 °C in darkness for 1 week before use. The mice were anesthetized with isoflurane and placed in a stereotaxic apparatus.Then the mice were injected through the brain lateral ventricle, with the solution with Aβ42 (5 μL), and the control group was injected with sterile normal saline containing DMSO (1%) of the same volume for 7 consecutive days.
IL-17Ab (BioXCell, clone 17F3) was dissolved in saline and injected into the lateral ventricle at 1 mg/kg in 3 μL on 12 h prior to Aβ42 injection and the 6th-day post-Aβ42 injection. The subsequent experiments were conducted 24 h after the injection of the IL-17Ab.
The hippocampus was homogenized in a buffer (pH 7.4) containing 50 mmol/L Tris–HCl, 150 mmol/L NaCl, 10 mmol/L NaF, 1 mmol/L Na3VO4, 5 mmol/L EDTA, 2 mM benzamidine, and 1 mM PMSF. The supernatants were collected after centrifugation of the tissue homogenates or cell lysate at 12000 rpm/min. Protein concentrations were determined with the bicinchoninic acid protein kit (Pierce, Rockford, USA). The proteins were loaded onto 10% gel (Invitrogen, Bis–Tris), separated by electrophoresis, and then transferred to a NC membrane. The images were visualized with an Odyssey infrared imaging system (LI-COR Biosciences, USA). For western blotting, the primary antibodies used were anti-IL-17 (Cell Signaling, #13838, 1:1000), anti-synapsinI (SYN, Millipore, AB1543, 1:1000), anti-postsynaptic density protein 95 (PSD-95, Cell Signaling, #2507, 1:1000), TRAF6 (Santa Cruz, sc-8409, 1:500), p-NF-κB p65 (Ser536) (Cell Signaling, #3033, 1:1000), anti-actin (actin, Abcam, ab6276, 1:10 000), and Lamin B1 (Abcam, ab16048, 1:1000).
The nuclear and cytoplasmic proteins preparation kit (P1200, Pulilai) was used to separate the nuclear and cytoplasmic NF-κB p65 components according to the manufacturer’s procedures for subsequent experiments.
Hippocampal neuronal cells were rinsed with phosphate buffered saline (PBS) and fixed in 4% paraformaldehyde for 8 min and permeabilized with 0.1% Triton X-100 in PBS for 30 min. After being blocked with 5% milk for 30 min, cells were incubated with primary antibodies conjugated to Alexa-fluo®488 or 594 against microtubule-associated protein-2 (MAP2, Abcam, 1:250), PSD-95 (Cell signaling, 1:250) at 4 °C overnight. The second antibody was then incubated at room temperature for 1 h and then rinsed in PBS three times. The nucleus was stained by DAPI (Sigma) for 5 min. Fluorescence images were obtained using the BX53 Olympus fluorescence microscope at a 20 × magnification and captured using the Olympus CellSens Standard software. Sholl analysis was applied to measure dendritic complexity. The length of dendritic arborization was analyzed and measured using a semi-automatized protocol via Imaris software (Bitplane, Inc.).
The open field is used to assess the tension, anxiety, and exploration activities of the mice. In brief, experimental mice were placed in a typical open field, and movements inside the field were tracked over a 5 min period. The total distance covered and central zone crossing were tracked and measured. The chamber was sanitized with 70% ethanol after each trial.
Novel objective recognition test (NORT)
The mice were taken to the new object recognition room 24 h before the test, and then we put the mouse into a 100 cm × 100 cm × 100 cm plastic container for 5 min without objects before the test. The next day, the mice reentered the container at the same starting point and were allowed for 5 min to familiarize themselves with A and B objects. After each period, the arena and objects were cleaned with 75% ethanol. Two hours after the familiarization period, the B object was replaced by the C object, and the mice were granted 5 min to explore the A object and C object. After 24 h, the C object was replaced with the D object, and the mice were also given 5 min to explore. The exploring time on each object was recorded.
The scene memory function of the mice was further detected by the fear conditioning test. Mice were placed into a square chamber (40 cm × 40 cm × 50 cm) with white board walls, a transparent front door, and a grid floor. On the day of training, the mice were allowed to explore in an enclosed training chamber for 180 s. The mice were then exposed to a pure tone for 30 s, followed by a 2 s foot shock (0.8 mA). At 60 s after delivery of the second shock, the mice were taken back to their home cages. 24 h later, mice were sent into the same chamber for 3 min without foot shock for fear memory tests. The time of freezing was measured using the Contextual NIR Video Fear Conditioning System (Med Associates).
Long-term potentiation (LTP)
After the mice were sacrificed, whole brains were immediately resected and soaked in ice-cold artificial cerebrospinal fluid (aCSF) saturated with 95% O2 and 5% CO2. Following sectioning at 300-μm thickness, the slices were incubated in oxygenated aCSF at 32 °C to recover for 40 min and at 20–25 °C to recover for 1 h. Then slices were transferred to a recording chamber and submerged in aCSF perfusion. Slices were laid in a chamber with an 8 × 8 microelectrode array (Parker Technology, Beijing, China) in the bottom planar (each 50 × 50 mm in size, with an interelectrode distance of 150 μm) and kept submerged in aCSF. Signals were acquired using the MED64 System (Alpha MED Sciences, Panasonic). The field excitatory postsynaptic potentials (fEPSP) in CA1 neurons were obtained by stimulating CA3 neurons. LTP was induced by applying three trains of high-frequency stimulation (100 Hz for 1 s, delivered 30 s apart). The LTP magnitude was quantified as the percentage change in the fEPSP slope (10–90%) taken during the 60-min interval after LTP induction .
Transmission electron microscopy (TEM)
After perfusion with fixatives hippocampus was dissected and slices were approximately 150 μm thick. The slices were fixed further by immersion in 0.1 M Na-cacodylate buffer containing 2.5% glutaraldehyde for 1 h at room temperature. Postfix with 1% OsO4 in 0.1 M PBS for 2 h at room temperature. Then dehydrate and infiltrate. Sections were photographed under a light microscope and then serially cut into semithin (2 μm thick) sections. The semithin sections were stained with 1% toluidine blue in 1% sodium borate and examined under the light microscope to locate the CA1 region. Selected semithin sections were further cut into serial ultrathin sections by using a Leica ultramicrotome. The ultrathin sections were examined under a HITACHI HT7800 TEM by an electron microscopy specialist from the Department of Ultrastructural Pathology Center, Renmin Hospital of Wuhan University. Synaptic densities were expressed as the number of synapses (identified via PSDs), per 100 μm2 of tissue.
FD Rapid Golgi Staining Kit PK 401(FD NEUROTECHNOLOGIES, INC, Columbia MO, USA) was used to measure the morphology of neuronal dendrites and dendrites’ spines. The mice were anesthetized by isoflurane and transcardially perfused with proximately 400 mL of normal saline containing 0.5% sodium nitrite, followed by 400 ml 4% formaldehyde solution and then 500 ml Golgi dye solution (5% chloral hydrate, 5% potassium dichromate, and 4% formaldehyde) over 2 h. And then, the brains were dissected into 5 mm × 5 mm sections and incubated in the staining solution for 3 days and in 1% silver nitrate solution for another 3 days in the dark. Finally, the brains were sliced using a vibrating microtome (Leica, Wetzlar, Germany) at a thickness of 100 μm. Images were observed under the microscope (BX53 Olympus fluorescence microscope, Japan).
All experiments were repeated at least three times. Results are expressed as mean ± standard deviation (SD) and analyzed using GraphPad Prism 8.0 statistical software. The normality heterogeneity of the data was tested. The differences were analyzed by the unpaired t-test or one-way ANOVA followed by the Bonferroni post hoc test. If the data were not normally distributed, the nonparametric test (Mann–Whitney test) was used to analyze the differences. The analyses of the quantification of the different proteins by western-blot (ratio) were performed on long-transformed data. p < 0.05 was considered statistically significant between groups.
The IL-17 level is increased in APP/PS1 mice
The cytokine, IL-17Ais involved in the learning and memory process in the central nervous system and its level was reported to be increased in Alzheimer's disease (AD) brain, while the effect of IL-17 on the course of Aβ has not been well defined. To investigate the role of IL-17 in neuropathological changes and memory deficits associated with Aβ pathophysiology, we used the transgenic mouse model of APP/PS1 mice, a progressive model of the amyloid plaques. The Elisa kit of IL-17 was used to detect the IL-17 level and the result showed that IL-17 was increased in the hippocampus of APP/PS1 mice when compared with the control mice (Fig. 1A). Furthermore, we performed western blotting and the result showed a significant increase in the protein levels of IL-17 from the APP/PS1mice (Fig. 1B, C), strongly supporting that the IL-17 level was increased in APP/PS1 mice.
IL-17 induces neuronal toxicity in primary hippocampal neurons
The above result showed that the IL-17 level was increased in APP/PS1 mice. However, the effect of IL-17 on neurodegenerative disease is still unclear. The hippocampus is an important part of the limbic system and is known to play a crucial role in memory function which is the reflection of synaptic plasticity [26, 27]. We then try to investigate the IL-17 effect on neuron in primary hippocampal neurons. The hippocampal primary neurons were divided into the control group and the IL-17 group (IL-17, 10 ng/mL). To investigate the underlying effect based on morphology,we examined the dendritic morphology of hippocampal primary neurons following treatment with IL-17 by using anti-MAP2 and PSD95 antibodies (Fig. 2A). When compared with the control, IL-17 resulted in an obvious decreased dendritic arborization complexity at all points farther than 50 μm from the cell body (Fig. 2B), as well as the total dendritic length (Fig. 2C). These findings suggest that IL-17 induced hippocampal neural damage.
Inhibition of IL-17 alleviates Aβ42-induced cognitive deficits and synaptic dysfunction
We confirmed that the IL-17 level was increased in APP/PS1 mice and cloud induce hippocampal neuronal damage. We therefore hypothesized that the IL-17 might been a target for intervention of Aβ42 induced-neurotoxicity. To test my hypothesis, Aβ42 was used to inject in lateral ventricle to induce the Aβ model. Then we explored whether IL-17Ab could ameliorate Aβ42-induced cognitive impairment and synaptic dysfunction. We divided our experiments into three groups and showed the flow chart for the experiments (Fig. 3A). The control group were injected with saline (5 μL) in the brain unilateral ventricle, and the Aβ42 model group were established after injecting in the brain unilateral ventricle with the solution Aβ42 (2.0 μg/μL, 5 μL). While the Aβ42 + IL-17Ab group was injected with Aβ42 (2.0 μg/μL, 5 μL), then IL-17Ab was injected into the lateral ventricle (1 mg/kg, 3 μL) on 12 h prior to Aβ42 injection and the 6th-day post-Aβ42 injection (Fig. 3A). We performed western blotting and the result showed a significant decrease in the protein levels of IL-17 from the Aβ42 + IL-17Ab mice (Fig. 3B, C) when compared with the Aβ42 mice. Furthermore, Elisa kit of IL-17 was used to detect the IL-17 level and the result showed that it was decreased in the hippocampus of Aβ42 + IL-17Ab mice (Fig. 3D).
Healthy C57BL/6 mice were randomly divided into 3 groups. Following the treatment, we again performed a couple of behavioral tests. In the open-field test, the total distance showed no significant differences among the three groups (Fig. 3E), indicating that the locomotion activity was not influenced by Aβ42 and IL-17Ab treatment, but the time of center duration was reduced in the Aβ42 group compared with the control, and ameliorated with the administration of IL-17Ab (Fig. 3F), implicating that inhibition of IL-17 might reduce anxiety. The novelty recognition experiment allows to explore short-term memory capacity, the results from this experiment showed that in the Aβ42 + IL-17Ab group, the curiosity of exploring new things was significantly higher when compared with the Aβ42 group, as the time spent exploring new object in 2 h and 24 h tests were significantly increased (Fig. 3G, H). And then, in the fear conditioning test, the Aβ42 + IL-17Ab group showed a significantly increase of freezing time when compared with the Aβ42 group, during 2 h and 24 h test (Fig. 3I, J), suggesting that inhibition of IL-17 could rescue the memory function. Taken together, these data demonstrate that inhibition of IL-17 attenuates Aβ42-induced cognitive anxiety, social ability impairments, and learning and memory.
To investigate the underlying the role of IL-17 in preventing behavioral alterations, we wonder whether IL-17 play a role in synaptic plasticity, and carried out some electrophysiology tests from hippocampal slices after behavioral tests. We explored whether hippocampal-dependent synaptic plasticity was detected by recording long-term potentiation (LTP). The LTP test showed that inhibition of IL-17 enhanced the slope of field excitatory postsynaptic potential (fEPSP) after high-frequency stimulation (HFS) compared with the Aβ42 group (Fig. 4A, B). We also observed the number of synapses in the hippocampus with TEM, and the results showed that the number of synapses per 100 μm2 CA1 area increased significantly after the IL-17Ab supplement compared with the Aβ42 model group mice (Fig. 4C, D). In addition, we further examined the spine density of hippocampal neurons (Fig. 4E). The Golgi staining showed a significant increase in the dendritic spine density of the Aβ42 + IL-17Ab rats compared with the Aβ42 group (Fig. 4F). We examined molecular changes in synapse-related proteins in the hippocampus. Western blotting (Fig. 4G) result showed a significant increase in the levels of SYN (Fig. 4H) and PSD95 (Fig. 4I) in the Aβ42 + IL-17Ab group. These results indicate that the inhibition of IL-17 alleviates Aβ42-induced cognitive deficits and synaptic dysfunction.
Inhibition of IL-17 attenuates Aβ42-induced neuronal damage by inactivation TRAF6-NF-κB signaling
To explore mechanism of restorative effect of IL-17Ab on learning and memory in Aβ42 + IL-17Ab mice. We performed western blotting to detect the levels of TRAF6. The results showed that the level of TRAF6 was increased in Aβ42 model mice compared with control mice, and IL-17Ab decreased the levels of TRAF6 compared with the Aβ42 group (Fig. 5A, B). Therefore, in order to explore NF-κB activation. We separate cytosolic and nuclear proteins, western blotting results showed that Aβ42 treatment upregulated the translocation of p65 from the cytoplasm to the nucleus (Fig. 5C–F). IL-17Ab obviously decreased Aβ42-induced nucleus phospho-NF-κB p65 (Ser536) translocation (Fig. 5C–F). Thus, these results suggested that IL-17Ab attenuates Aβ42-induced neuronal damage by inactivation TRAF6/NF-κB signaling.
Neuroinflammation plays a critical role in the pathophysiology of Aβ-induced neurotoxicity and cognitive decline [28,29,30]. In the present study, we here found that IL-17 was increased in APP/PS1 mice, we showed that IL-17 is involved in Aβ-induced neurotoxicity.
IL-17 is a pro-inflammatory cytokine produced by various types of cells including CD4 T which are categorized as a new subset called Th17 cells . Th17 cells are the main cellular mediators responsible for immune-mediated damages that polarize to the site of inflammation in presence of noxious or inflammatory stimuli [31, 32]. However, the effect of cytokine IL-17 remains poorly understood and very little is known about its pathophysiological role in the regions of the CNS usually compromised in disease . To investigate the role of IL-17 in neuropathological changes and memory deficits, the IL-17 (10 ng/mL) was treated in hippocampal primary neurons, and the dendrintic morphology of hippocampal primary neurons was stained by using anti-MAP2 and PSD95 antibodies. And results showed that when compared with the control, IL-17 resulted in an obvious decreased dendritic arborization complexity at all points farther than 50 μm from the cell body, as well as the total dendritic length. These findings suggest that IL-17 induced hippocampal neural damage.
We therefore hypothesized that the IL-17 might been a target for intervention of Aβ42 induced-neurotoxicity. To test my hypothesis, we explored whether IL-17Ab could ameliorate Aβ42-induced cognitive impairment and synaptic dysfunction. Interestingly, Using Aβ42 mice, the results showed that the level of IL-17 was increased in Aβ42 model mice, andIL-17Abcould ameliorate Aβ-induced neurotoxicity and cognitive decline in C57BL/6 mice.
Then, to explore mechanism of restorative effect of IL-17Ab on learning and memory. Mechanistically, we show that IL-17Ab ameliorates the neuronal damage in Aβ42 model mice which is mediated by inhibition of IL-17 signaling. The cellular levels of TRAF6 and nuclear phospho-NF-κB p65 (Ser536) were elevated in Aβ42 model mice, and administration of IL-17Ab reduced the levels. IL-17 is reported to activate NF-κB signaling through IL-17R by recruiting TRAF6. Our study showed that IL-17Ab may inactivate NF-κB and reduce its translocation from the cytoplasm to the nucleus. NF-κB signaling in the central neurons system has a vital role by regulating certain functions like neuronal plasticity and neuronal growth , and the inhibition of the NF-κB plays a novel target in Alzheimer's disease therapy . IL-17A binded ACT1 to IL-17-RA allows incorporation of tumour necrosis factor receptor-associated factor 6 (TRAF-6) adaptor protein into the complex, which in turn leads to activation of inhibitory κB kinase, liberating the transcription factors nuclear factor κB (NF-κB), our results showed that Aβ42 treatment upregulated the translocation of p65 from the cytoplasm to the nucleus. IL-17Ab obviously decreased Aβ42-induced nucleus phospho-NF-κB p65 translocation. Thus, these results imply that IL-17 induces neuronal damage by activation of IL-17/ TRAF6/ NF-κB pathway.
The key finding in our study was that Aβ mediated neurotoxicity via IL-17 inflammatory factor. Our results showed that inhibition of IL-17 could reverse the Aβ-induced neurotoxicity. In the future, we will apply this basic research to the clinical application of IL-17 inhibition to improve cognitive impairment in patients with clinical Alzheimer's disease. That will be a new challenge.
Conclusively, we have described the pathogenic role of IL-17 in Aβ induced-synaptic dysfunction and cognitive deficits. Using Aβ42 mice, the results showed that the level of IL-17 was increased in Aβ42 model mice, and IL-17Ab could ameliorate Aβ-induced neurotoxicity and cognitive decline in C57BL/6 mice by downregulation the TRAF6/ NF-κB pathway (Fig. 6), which provides new clues for the mechanism of Aβ-induced cognitive impairments, and a basis for therapeutic intervention.
Availability of data and materials
The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
Enzyme-linked ImmunoSorbent assays
Field excitatory postsynaptic potential
Transcription factors nuclear factor κB
Novel objective recognition test
Postsynaptic density protein 95
Transmission electron microscopy
Tumour necrosis factor receptor-associated factor 6
Phosphate buffered saline
Artificial cerebrospinal fluid
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The authors would like to thank Yingxia Jin and Lina Zhou from Central Laboratory, Renmin Hospital of Wuhan University, for their technical assistance.
This work was supported by the National Natural Science Foundation of China (No.8187032070) and the Fundamental Research Funds for the Central Universities (No.2042019kf0081).
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This study was approved by the Animal Care Committees of T the Ethics Committee of Renmin Hospital, Wuhan University (IACUC Issue No. WDRY2018-K033), in accordance with international regulations. The study is reported in accordance with ARRIVE guidelines.
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Liu, Y., Meng, Y., Zhou, C. et al. Activation of the IL-17/TRAF6/NF-κB pathway is implicated in Aβ-induced neurotoxicity. BMC Neurosci 24, 14 (2023). https://doi.org/10.1186/s12868-023-00782-8
- Synaptic dysfunction
- Cognitive decline