Memory impairments in rodent depression models: a link with depression theories

The takeaway

Rodent models of depression consistently produce impairments in broad memory domains, mirroring patient deficits. These cognitive problems arise from interconnected neurochemical, hormonal, inflammatory, oxidative, and neurotrophic changes.

The science

Memory dysfunction in depression models aligns with key biological theories. Reductions in serotonin, dopamine, and acetylcholine impair cognition, while glutamate and GABA disruptions vary by model. Stress and other hormonal imbalances damage hippocampal and prefrontal circuits. Neuroinflammation, marked by cytokines and kynurenine shifts, drives spatial and recognition deficits. Oxidative stress further weakens memory, while antioxidants can reverse these effects. Reduced BDNF, NGF, and neurogenesis highlight impaired plasticity, with recovery of neurotrophic signaling improving cognition. Together, these mechanisms converge on prefrontal–hippocampal dysfunction, pointing to multiple therapeutic targets.

Why it matters

Cognitive deficits are a disabling aspect of depression and are inadequately treated by existing medications. Focusing on neurotransmission, hormones, inflammation, oxidative stress, and neurotrophins could pave the way for new antidepressants with enhanced cognitive improvements.

Orginal article

https://doi.org/10.1016/j.pnpbp.2023.110774