Interneurons in the CA1 stratum oriens expressing αTTP may play a role in the delayed-ageing Pol μ mouse model

• Published in: Molecular and cellular neuroscience Vol. 130; p. 103960
• Main Authors: Selva-Clemente, J., Marcos, P., González-Fuentes, J., Villaseca-González, N., Lagartos-Donate, M.J., Insausti, R., Arroyo-Jiménez, M.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2024
• Subjects: CA1; Calcium-binding proteins; Hippocampus; Immunohistochemistry; Pol μ delayed-ageing mice; Stratum oriens; αTTP; Immunohistochemistry; Pol μ delayed-ageing mice; pyl; αT; DG; IHC; PV; VitE; DABCO; αTTP; CA1; Pol μ; CA3; CA2; st.or; Calcium-binding proteins; CBPs; CB; sr; PBS; DAB; OS; TBS; gl; IR; Stratum oriens; alv; CR; INs; PB; slm; SEM; PCR; Hippocampus
• ISSN: 1044-7431; 1095-9327; 1095-9327
• DOI: 10.1016/j.mcn.2024.103960

Neurodegeneration associated with ageing is closely linked to oxidative stress (OS) and disrupted calcium homeostasis. Some areas of the brain, like the hippocampus – particularly the CA1 region – have shown a high susceptibility to age-related changes, displaying early signs of pathology and neuronal loss. Antioxidants such as α-tocopherol (αT) have been effective in mitigating the impact of OS during ageing. αT homeostasis is primarily regulated by the α-tocopherol transfer protein (αTTP), which is widely distributed throughout the brain – where it plays a crucial role in maintaining αT levels within neuronal cells.
This study investigates the distribution of αTTP in the hippocampus of 4- and 24-month-old Pol μ knockout mice (Pol μ−/−), a delayed-ageing model, and the wild type (Pol μ+/+). We also examine the colocalisation in the stratum oriens (st.or) of CA1 region with the primary interneuron populations expressing calcium-binding proteins (CBPs) (calbindin (CB), parvalbumin (PV), and calretinin (CR)). Our findings reveal that αTTP immunoreactivity (-IR) in the st.or of Pol μ mice is significantly reduced. The density of PV-expressing interneurons (INs) increased in aged mice in both Pol μ genotypes (Pol μ−/− and Pol μ+/+), although the density of PV-positive INs was lower in the aged Pol μ−/− mice compared to wild-type mice. By contrast, CR- and CB-positive INs in Pol μ mice remained unchanged during ageing.
Furthermore, double immunohistochemistry reveals the colocalisation of αTTP with CBPs in INs of the CA1 st.or. Our study also shows that the PV/αTTP-positive IN population remains unchanged in all groups. A significant decrease of CB/αTTP-positive INs in young Pol μ−/− mice has been detected, as well as a significant increase in CR/αTTP-IR in older Pol μ−/− animals. These results suggest that the differential expression of αTTP and CBPs could have a crucial effect in aiding the survival and maintenance of the different IN populations in the CA1 st.or, and their coexpression could contribute to the enhancement of their resistance to OS-related damage and neurodegeneration associated with ageing.
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•αTTP is significantly reduced in CA1 st.or of Pol μ knockout mice (Pol μ−/−).•Parvalbumin expressing interneurons in the st.or are increased in aged Pol μ mice.•Interneurons containing calcium binding proteins colocalise with αTTP.•αTTP may influence the resistance of specific interneuron populations in Pol μ mice.