Neurobehavioral Effects of Diesel Exhaust Exposure in Mice: A Systematic Review

Abstract

Background: Diesel exhaust (DE) is a major source of urban fine and ultrafine particulate matter and a classified human carcinogen, yet its effects on the brain and behaviour are far less characterised than its respiratory and cardiovascular effects. Mouse models allow exposure, developmental timing and genotype to be controlled, but the neurobehavioural literature on DE has not been systematically synthesised.

Objectives: To systematically review controlled studies of DE, diesel exhaust particles (DEP) and DE-derived secondary organic aerosol (DE-SOA) in mice that measured at least one neurobehavioural outcome, and to describe exposure paradigms, behavioural domains affected, sex- and window-specific effects, and methodological quality.

Methods: The review followed PRISMA 2020. Studies were identified through structured web searching and citation chasing conducted over a three-month period (May–July 2026), without bibliographic-database exports. Eligible studies were in vivo experiments in mice comparing diesel exhaust (DE), diesel exhaust particulate (DEP), or diesel exhaust–secondary organic aerosol (DE-SOA) exposure with clean-air or vehicle controls and reporting behavioural endpoints. Studies involving other species, non-diesel particulate matter, single chemical constituents, in vitro systems, and conference abstracts were excluded. Reporting of randomisation and blinding was appraised narratively against SYRCLE domains. Findings were synthesised narratively by behavioural domain, with vote counting by direction of effect.

Results: Twenty-eight studies published between 2008 and 2025 were included: 15 used developmental (prenatal, perinatal or neonatal) exposure and 13 used adult exposure; 22 used whole-body inhalation, 2 parenteral and 2 airway instillation or aspiration (intranasal, oropharyngeal), with route not stated for 2. Where reported, particle concentrations ranged from about 50 µg/m³ to 19 mg/m³. Adverse effects on learning and memory were reported in 14 of 18 studies that tested it, anxiety-like behaviour in 4 of 5, depression-like behaviour in 4 of 4, and social, repetitive or aggressive behaviour in all 4 studies that tested these domains. Locomotor and motor effects were inconsistent in direction. Null or slight findings came mainly from neonatal, acute and resuspended-DEP designs. Roughly two-thirds of studies originated from three research groups, most tested males only (at least 13 of 28), and exposure characterisation and blinding were reported unevenly.

Conclusions: Preclinical evidence supports a neurobehavioural signal for DE exposure, most consistently for hippocampus-dependent cognition, mood-like behaviour and developmental social and repetitive phenotypes. Heterogeneity in exposure type, route and timing, limited female data, clustering within a few laboratories and incomplete reporting limit confidence. Standardised exposure reporting, inclusion of both sexes, blinded and pre-registered designs, and independent replication are priorities.