Sex-dependent alterations in motor cortex linking spinal cord injury to long-term neurodegeneration risk

ABSTRACT: Patients with spinal cord injuries often suffer from multiple complications, including cognitive impairments after recovering from the primary wound. The molecular mechanism linking spinal cord injury and brain abnormality, however, remains elusive and has been largely attributed to neuroinflammation. In this work, we assessed persistent compositional and molecular changes in the motor cortex at 30 days post injury, a commonly perceived chronic stage, using a rat T10 contusion injury model. Brain slices and neurons isolated from the motor cortex were assessed using immunohistochemistry and RNA-sequencing, respectively. We observed significant changes in cellular compositions in the motor cortex including a decreased neuron to astrocyte ratio, and alterations in the morphology of neurons and astrocytes, indicating changes in functionality. Comparison of transcriptomic data collected at a sub-acute stage, namely 7 days post injury, with that at 30 days post injury, identified persistent and de novo (genes uniquely altered at 30 dpi.) changes that occur primarily after recovery of the spinal cord injury, enriched for neuronal and synaptic function related pathways. Strikingly, male and female rats showed distinct transcriptomic alterations at 30 days post-injury, with males showing neuron-related changes and females showing alterations in metabolism- and extracellular matrix–related pathways. These molecular differences were accompanied by better functional recovery in females, as reflected by significantly higher BBB scores, suggesting sex-dependent molecular changes induced in the motor cortex. Collectively, our study lays the foundation for understanding sexual dimorphism in brains after spinal cord injury and provides a plausible connection between spinal cord injury and increased risk for neurodegeneration later in life.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE326470 | GEO | 2026/04/06

REPOSITORIES: GEO