RT Journal Article
T1 Sex-dependent worsening of NMDA-induced responses, anxiety, hypercortisolemia, and organometry of early peripheral immunoendocrine impairment in adult 3xTg-AD mice and their long-lasting ontogenic modulation by neonatal handling
A1 Baeta Corral, R.
A1 Fuente Del Rey, María Mónica De La
A1 Giménez Llort, L.
AB The neuroimmunomodulation hypothesis for Alzheimer’s disease (AD) postulates that alterations in the innate immune system triggered by damage signals result in adverse effects on neuronal functions. The peripheral immune system and neuroimmunoendocrine communication are also impaired. Here we provide further evidence using a longitudinal design that also studied the long-lasting effects of an early life sensorial intervention (neonatal handling, from postnatal day 1–21) in 6-month-old (early stages of the disease) male and female 3xTg-AD mice compared to age- and sex-matched non-transgenic (NTg) mice with normal aging. The behavioral patterns elicited by the direct exposure to an open field, and the motor depression response evoked by NMDA (25 mg/kg, i.p) were found correlated to the organometry of peripheral immune-endocrine organs (thymus involution, splenomegaly, and adrenal glands’ hypertrophy) and increased corticosterone levels, suggesting their potential value for diagnostic and biomonitoring.The NMDA-induced immediate and depressant motor activity and endocrine (corticosterone) responses were sensitive to sex and AD-genotype, suggesting worse endogenous susceptibility/neuroprotective response to glutamatergic excitotoxicity in males and in the AD-genotype. 3xTg-AD females showed a reduced immediate response, whereas the NTg showed higher responsiveness to subsequent NMDA-induced depressant effect than their male counterparts. The long-lasting ontogenic modulation by handling was shown as a potentiation of NMDA-depressant effect in NTg males and females, while sex × treatment effects were found in 3xTg-AD mice. Finally, NMDA-induced corticosterone showed sex, genotype and interaction effects with sexual dimorphism enhanced in the AD-genotype, suggesting different endogenous vulnerability/neuroprotective capacities and modulation of the neuroimmunoendocrine system.
PB Elsevier
SN 0166-4328
YR 2023
FD 2023-02-13
LK https://hdl.handle.net/20.500.14352/124133
UL https://hdl.handle.net/20.500.14352/124133
LA eng
NO Baeta-Corral, De la Fuente, & Giménez-Llort. (2023). Sex-dependent worsening of NMDA-induced responses, anxiety, hypercortisolemia, and organometry of early peripheral immunoendocrine impairment in adult 3xTg-AD mice and their long-lasting ontogenic modulation by neonatal handling. Behavioural Brain Research, 438. https://doi.org/10.1016/J.BBR.2022.114189
NO This work was funded by Instituto de Salud Carlos III – Subdirección General de Evaluación y Fomento de la Investigación (AES-PI10/00283), co-financed by the European Regional Development Fund (ERDF), 2017-SGR-1468 and 2020-UAB-GE-260408 to L.G.-L. R.B.-C received a predoctoral grant FI-DGR (2012FI B1 00198) from Secretaria d’Universitat i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya.
NO Instituto de Salud Carlos III
NO European Commission
NO Generalitat de Catalunya
DS Docta Complutense
RD 22 dic 2025