2026 ECNP Congress

EP02-2001

Curcumin-loaded liposomes are able to prevent some schizophrenia-related alterations in a maternal immune activation model

Raquel Chávez Valencia — N. Miguel-Ramiro, A. López, M. Desco, M.L. Soto-Montenegro · Instituto de Investigación Sanitaria Gregorio Marañón, Biomedical Imaging and Instrumentation Group, Madrid, Spain

2026 ECNP Congress

Introduction

Inflammation and oxidative stress (IOS) are central mechanisms in the pathophysiology of schizophrenia (SCZ), highlighting anti-IOS compounds as potential preventive and therapeutic strategies. Curcumin (CUR), a natural polyphenol with strong anti-IOS properties1, has received particular attention. However, its clinical application is limited by poor water solubility and low bioavailability. To overcome these limitations, our study investigates curcumin-loaded liposomes (LipoCUR) as a dietary intervention and evaluates their ability to prevent neuroanatomical and behavioural alterations in the maternal immune stimulation (MIS) model of SCZ.

Methods

Pregnant Wistar rats were administered Poly I:C (4 mg/kg) or Saline on gestational day 15. Male offspring received oral LipoCUR (10 mg/kg) during adolescence from postnatal day (PND) 35 to PND70. Animals were assigned to 4 groups: Saline-naïve, Saline-LipoCUR, MIS-naïve and MIS-LipoCUR. Behavioral assessments were conducted at PND 70 by the novel place recognition (NPR), novel object recognition /NOR) and open field (OF) tests. At PND100, brain structural alterations were evaluated using T2-weighted magnetic resonance imaging3. Volumetric brain changes were evaluated through manual segmentation of regions of interest (ROIs)4. Also, a voxel-based morphometry analysis of grey (GM) and white matter (WM) were performed. Statistical analyses were performed using ANOVA and Kruskal-Wallis tests.

Results/Discussion

Behavior: Lipo-CUR did not produce significant effects on locomotion or exploratory behavior (rearing), although a trend toward improvement was observed in MIS-offspring.A similar pattern was found in the short-term memory task, where no significant differences were detected, but modest improvements were suggested, indicating limited behavioral efficacy under the present conditions.

ROI analysis: MIS-offspring showed reduced dorsal hippocampal volume in, which was not prevented by LipoCUR. However, LipoCUR effectively prevented ventricular enlargement in MIS-offspring, suggesting a selective effect on neuroanatomical alterations.

Morphometric analysis: A) Pharmacological effect: LipoCUR exerted differential effects in Saline and MIS offspring. In saline-offspring, LipoCUR induced GM enlargements in cortical regions and the caudate-putamen. In contrast, MIS-offspring exhibited subtle GM changes, primarily detected at the nucleus accumbens and caudate-putamen. Notably, LipoCUR induced more pronounced WM changes in MIS-offspring than in controls, with significant enlargements in WM fibres found in the cerebellum and brainstem. B) Treatment effect: When comparing MIS to Saline-offspring, LipoCUR induced enlargements in the caudate-putamen, RSA and cerebellum, as well as shrinkages in hypothalamic tracts,

Conclusions

Adolescent LipoCUR administration produced modest behavioral effects but elicited selective neuroanatomical modulation in adult MIS-offspring. While hippocampal volume deficits were not reversed, LipoCUR prevented ventricular enlargement and induced region-specific changes in GM and WM. These findings suggest that LipoCUR may partially counteract some structural alterations associated with the MIS model. Although the overall efficacy was limited, these findings encourage further research into optimized dosages, treatment windows and improved CUR formulations to enhance its therapeutic impact, as well as additional studies to elucidate the underlying mechanisms of action.

Novelty

No study has yet explored the effects of LipoCUR in an animal model of schizophrenia, or its impact on brain and cognitive function.

Impact

LipoCUR produced modest and region-specific neuroanatomical effects, with limited behavioural improvements, suggesting restricted neurobiological efficacy under the present experimental conditions.

References

References

  1. Hatami, M., et al., Endocr Metab Immune Disord Drug Targets, 2019. 19(3): p. 247-258.
  2. Lamanna-Rama, N., et al., Psychiatry Res, 2024. 331: p. 115643.
  3. Paxinos, G., and Watson, C., The Rat Brain in Stereotaxic Coordinates: Hard Cover Edition 7th ed., Elsevier Science; 2013.
  4. Sundt Curcumin, Sundt Nutrition Acknowledgement This work was funded by grant PID2021-128862OB-I00 funded by MICIU/AEI /10.13039/501100011033 and by FEDER, UE; CIBER de Salud Mental - ISCIII (project number CB07/09/0031); Comunidad de Madrid (project S2022/BMD-7403 RENIM-CM); Delegación del Gobierno para el Plan Nacional sobre Drogas correspondiente a fondos del Mecanismo de Recuperación, Transformación y Resiliencia de la Unión Europea (project EXP2022/008917), Delegación del Gobierno para el Plan Nacional sobre Drogas (project 2024I090); II Edition of iSanidad y Herbalife Nutrition Grant; and Instituto de Salud Carlos III (ISCIII), through the project “ PT23/00027“ and co-funded by the European Union. RCV was supported by grant Intramural Programme IiSGM for the Promotion of R&D&I 2025, Sub-programme “Predoctoral training contract for established groups