Pregnancy History and Loss of Normal PSEN2 Function Impact Female Late-Life Cognitive Processing, Inhibitory Signaling, and Gliosis

In aged female PSEN2 knockout and wild-type mice, parity history does not alter hippocampally mediated spatial working memory, but it is linked to changes in inhibitory signaling and gliosis markers.

• Why it matters: Female-specific life history may modify how AD risk factors shape late-life brain function, yet parity effects on late-life outcomes are inconsistent and need mechanistic testing.
• What they did: Female PSEN2 KO and WT mice were tested at 10–15 months in the T-maze and Open Field Test, then assessed by immunofluorescence for inhibitory neuron markers and glial biology across hippocampal subregions and related areas.
• The result: PSEN2 deficiency and multiparity reduced Open Field locomotor behavior, multiparity also reduced center exploration (p=0.0045), and parity generally increased inhibitory marker expression (p=0.017, 0.021, 0.035) while shifting astrocyte/microglia and oligodendrocyte marker expression without synergy.

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