Dataset Information

Neuroinflammatory Stress Preferentially Impacts Synaptic MAPK Signaling and Mitochondria in Excitatory Neurons

ABSTRACT: In this study, we have applied cell type-specific in vivo biotinylation of proteins (CIBOP) to label Camk2a excitatory neuronal proteomes, and imposed differential centrifugation to prepare synaptosome-enriched fractions, followed by proteomic analysis of biotinylated neuronal proteins. This approach allowed us to obtain the native-state proteome of crude synaptosomes containing presynaptic (mitochondria and synaptic vesicles) and postsynaptic compartments of excitatory neurons from mouse brain, while directly contrasting them with the whole neuronal proteome. Next, we used the systemic LPS-induced neuroinflammation model to activate microglia in an AD-relevant manner, and examined how the synaptic compartment of excitatory neurons responds to neuroinflammatory stress, in contrast with the somatodendritic compartment. We observed that the effects of neuroinflammation on the synaptic compartment were indeed distinct from the somatodendritic compartment, suggestive of compartment-specific effects of neuroinflammation.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Excitatory Synapse

DISEASE(S): Alzheimer's Disease

SUBMITTER: UPASNA SRIVASTAVA

LAB HEAD: UPASNA SRIVASTAVA

PROVIDER: PXD068874 | Pride | 2026-04-13

REPOSITORIES: Pride

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Neuroinflammatory stress preferentially impacts synaptic MAPK signaling and mitochondria in excitatory neurons.

Espinosa-Garcia Claudia C Srivastava Upasna U Kumar Prateek P Kour Dilpreet D Malepati Sneha S Tobin Brendan R BR Xiao Hailian H Sunna Sydney S Bowen Christine A CA Cheng Lihong L Bagchi Pritha P Duong Duc M DM Whitworth Ted J TJ Liu Xinran X Seyfried Nicholas T NT Wood Levi B LB Faundez Victor V Rangaraju Srikant S

Molecular neurodegeneration advances 20260324 1

<h4>Background</h4>Understanding synapse-specific effects of neuroinflammation can provide mechanistic and therapeutically relevant insights across the spectrum of neurological diseases.<h4>Methods</h4>We applied neuron-specific proteomic biotinylation <i>in vivo</i>, differential centrifugation of brain for crude synaptosome enrichment (P2 fraction) and mass spectrometry (MS) analysis of biotinylated proteins to derive native-state proteomes of Camk2a-positive neurons and their corresponding P2 ...[more]

PMID: 41953673

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