Metabolites were identified using characteristic chromatographic retention time and mass spectrometric multiple-reaction monitoring (MRM) parameters, as described.
"],"repository":["MetaboLights"],"study_status":["Public"],"ptm_modification":[""],"instrument_platform":["Liquid Chromatography MS - positive - reverse-phase"],"chromatography_protocol":["Chromatographic separation was done on a 100 x 2.1-mm i.d., 1.8-µm UPLC HSS T3 column (Waters Acquity) with mobile phases A (0.1% formic acid in water) and B (0.1% formic acid in acetonitrile) at a flow rate of 0.6 ml/min and column temperature 45°C. The gradient used was as follows: 0.5 min at 4% B; linear increase to 10% B over 2 min, increase to 28% B over 2.5 min, then washing by increase to 95% B in 0.1 min, followed by 2 min hold at 95% B, back to 4% B over 0.1 min, and equilibration at 4% B for 2.8 minutes. Samples kept at 4°C were automatically injected in a volume of 1 µl.
"],"publication":["Disruption of the Brain-Spleen Axis Impairs Monocyte-Microglia Communication and Accelerates Disease Progression in a Mouse Model of Amyloidosis."],"submitter_name":["Alexander Brandis"],"submitter_affiliation":["Weizmann Institute"],"organism_part":["blood plasma","spleen","solvent"],"technology_type":["mass spectrometry assay"],"disease":[""],"extraction_protocol":["A 10-µl aliquot of each sample and 10 µl of internal standard (IS; norepinephrine-d6, dopamine-d4, and serotonin-d4 from C.D.N. Isotopes, 400ng/ml each) were added to 70 µL of borate buffer (200 mM, pH 8.8) at 25°C, mixed, and then 20 µl of Aqc reagent (10 mM dissolved in 100% ACN) was added and immediately mixed. The samples were heated at 55°C for 10 minutes, then filtered into nanofilter vials (0.2-µm PES, Thomson) for analysis.
"],"organism":["Mus musculus","blank"],"full_dataset_link":["https://www.ebi.ac.uk/metabolights/MTBLS14615"],"author":["Alexander Brandis. alexander.brandis@weizmann.ac.il.","Tommaso Croese. tommaso.croese@immunobrain.com.","Michal Schwarts. Weizmann Institute of Science. michal.schwarts@weizmann.ac.il."],"data_transformation_protocol":["Standard curves of the neurotransmitter mix at a range of 0.001-10 uM were used. MassLynx and TargetLynx software (v.4.2, Waters) were used to acquire and analyze the data.
"],"study_factor":["Organ"],"submitter_email":["alexander.brandis@weizmann.ac.il"],"sample_collection_protocol":["The detection of Norepinephrine, Epinephrine, Dopamine, and Serotonin both plasma and spleen homogenates were used. For plasma, blood was collected in tubes containing 2 μL heparin, briefly vortexed, and then centrifuged at 3,000 g for 15 min at 4 °C. Supernatant plasma was aliquoted and stored at ULT. The spleens were weighed and then disrupted using scissors. For each milligram of spleen, 5 µL of PBS1x with 1:1000 of Protease Inhibitor Cocktail (Sigma, P8340) was added, and the tissue was thoroughly resuspended. The disrupted spleen was transferred to a tissue homogenizer. After homogenization, the homogenate was centrifuged at 10,000g for 10 minutes, and supernatant was collected.
"],"omics_type":["Metabolomics"],"study_design":["Metabolomics","Mus musculus","blank","microglial cell","Waters Xevo TQ-S","targeted analysis","spleen","Alzheimer disease","Waters ACQUITY UPLC I-Class System","experimental sample","blood plasma","monocyte","solvent","experimental blank","selected reaction monitoring","Denervation"],"curator_keywords":["Metabolomics","Mus musculus","microglial cell","blank","Waters Xevo TQ-S","targeted analysis","spleen","Alzheimer disease","Waters ACQUITY UPLC I-Class System","experimental sample","blood plasma","monocyte","solvent","experimental blank","selected reaction monitoring","Denervation"],"mass_spectrometry_protocol":["Mass detection was carried out using electrospray ionization in positive mode. Argon was used as the collision gas with flow 0.10 ml/min. The capillary voltage was set to 3.0 kV, source temperature - 150°C, desolvation temperature - 650°C, desolvation gas flow - 800 L/min, cone voltage 20V, collision energy 25eV. Analytes were detected by monitoring of fragment ion 171 m/z produced from corresponding precursor ions: 354 [epinephrine + Aqc + H]+, 347 [serotonin + Aqc + H]+, 340 [norepinephrine + Aqc + H]+, and 324 [dopamine + Aqc + H]+ m/z; for IS: 351 [serotonin-d4 + Aqc + H]+, 346 [norepinephrine-d6 + Aqc + H]+, and 328 [dopamine-d + Aqc + H]+ m/z.
"],"additional_accession":[]},"is_claimable":false,"name":"Disruption of the Brain-Spleen Axis Impairs Monocyte-Microglia Communication and Accelerates Disease Progression in a Mouse Model of Amyloidosis","description":"Alzheimer’s disease (AD) is characterized by a prolonged asymptomatic phase before cognitive decline emerges, yet the mechanisms driving symptom onset remain unclear. Here, we hypothesized that the transition from asymptomatic to symptomatic disease is linked to dysfunction of brain–immune communication. Retrograde neuronal tracing in the 5xFAD mouse model of amyloidosis reveals reduced brain–spleen connectivity at advanced disease stages. To probe the functional role of the brain–spleen axis in coping with disease, we denervated the splenic nerve at an early presymptomatic stage. This intervention accelerates cognitive decline, impairs splenic hematopoiesis, diminishes monocyte recruitment to the brain, disrupts monocyte–microglia signaling networks, and reduces the transition of microglia from a homeostatic to a disease-associated (DAM) state. Conversely, enhancing splenic noradrenergic input increases hematopoiesis, restores monocyte homing to the brain, and delays cognitive impairment. The protective role of splenic monocytes was independently validated in a retinal cytotoxic injury model, in which splenic denervation impairs post-insult survival of retinal ganglion cells. Together, these findings identify an active brain–spleen circuit in regulating monocyte recruitment and establish peripheral monocytes as important drivers of microglial state transitions and disease progression.","dates":{"publication":"2026-06-01","submission":"2026-05-29"},"accession":"MTBLS14615","cross_references":{}}