Interneurons in the CA1 stratum oriens expressing αTTP may play a role in the delayed-ageing Pol µ mouse model.
Mol Cell Neurosci
; 130: 103960, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-39179163
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Parvalbuminas
/
Envelhecimento
/
Proteínas de Transporte
/
Região CA1 Hipocampal
/
Interneurônios
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Neurosci
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Espanha
País de publicação:
Estados Unidos