Evidence map›Paper›PMID 41324815›Full record

ArticleMolecular neurobiology2025

Sex-Specific Molecular Architecture of Microglia-Mediated Neuronal Pruning Across the Human Lifespan.

Cristina Sanfilippo, Paola Castrogiovanni, Rosa Imbesi, Michele Vecchio, Michelino Di Rosa

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Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Cristina SanfilippoNeurologic Unit, AOU "Policlinico-San Marco", Department of Medical, Surgical Sciences and Advanced Technologies, GF, Ingrassia, University of Catania, Via Santa Sofia 78, Catania, Sicily, 95100, Italy.ORCID http://orcid.org/0000-0001-7812-1564
Paola CastrogiovanniDepartment of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy.ORCID http://orcid.org/0000-0001-5873-2456
Rosa ImbesiDepartment of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy.ORCID http://orcid.org/0000-0003-4228-4163
Michele VecchioDepartment of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy.ORCID http://orcid.org/0000-0001-5254-3283
Michelino Di RosaDepartment of Biomedical and Biotechnological Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy. mdirosa@unict.it.ORCID http://orcid.org/0000-0002-1837-9325

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sex-specific differences in neurodegenerative disease susceptibility suggest distinct molecular mechanisms underlying brain aging between males and females. In this study, we investigated transcriptomic profiles of complement system components, microglial markers, and astrocyte/neuronal proteins across the lifespan to elucidate sex-dependent synaptic pruning mechanisms. Comprehensive transcriptomic analysis was performed on brain tissue samples spanning multiple age groups and regions, examining expression patterns of complement genes (C1QA, C1QB, C1QC, C1R, C1S, C3, ITGAM, ITGB2), microglial markers (TMEM119, P2RY12, CSF1R, NLRP3, TREM2, AIF1), and astrocytic, neuronal, and tissue markers (MAP2, SYP, SNAP25, MAPT, GFAP, CHI3L1). Complement system components demonstrated pronounced sex bias. Males exhibited distinct U-shaped age-related patterns, with middle-late childhood (MLC) consistently showing the highest expression for most genes, decreasing in middle age, followed by partial reactivation in nonagenarians, and then a further reduction in centenarians. An oscillatory trajectory across the lifespan was observed in females, with a peak in centenarians. Regional analysis revealed diencephalic predominance and occipital suppression patterns. Microglial activation markers exhibited complex sex-dependent patterns, with males showing higher expression during childhood/adolescence and females demonstrating an elevation in advanced age. These genes displayed limbic and diencephalic enrichment with cerebellar reduction. Neuronal/astrocytic markers showed opposing trajectories: neuronal markers (MAP2, SNAP25, SYP, MAPT) generally declined with age, while astrocytic markers (GFAP, CHI3L1) increased. Males demonstrated compartmentalized gene clustering, while females showed integrated neuro-microglial networks. Functional enrichment analysis confirmed these networks coordinate complement-mediated synapse pruning, representing systematic age-related synaptic remodeling mechanisms that differ fundamentally between sexes and may influence neurodegenerative susceptibility patterns. These findings demonstrate that female brains maintain heightened complement-mediated synaptic pruning throughout aging, representing a double-edged mechanism that may confer adaptive plasticity while increasing vulnerability to neurodegeneration. Male brains exhibit more stable neuronal environments with reduced glial activation, potentially underlying sex-specific trajectories in brain aging and neurodegenerative disease susceptibility.

Indexed as

LongevityMicrogliaNeuronal PlasticityNeuronsSex CharacteristicsAdolescentAdultAgedAged, 80 and overAgingBrainChildFemaleHumansMaleMiddle AgedBrain agingComplement systemMicroglial activationNeuronal pruningSex differences

Identifiers

PMID41324815

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