Jastrzebska Joanna, Frankowska Malgorzata, Wesołowska Julita, Filip Malgorzata, Smaga Irena
Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, 12 Smętna Street, 31-343 Kraków, Poland.
Laboratory of Microscopic Imaging, Maj Institute of Pharmacology Polish Academy of Sciences, CEPHARES, 12 Smętna Street, 31-343 Kraków, Poland.
Curr Neuropharmacol. 2025;23(3):329-348. doi: 10.2174/1570159X23666241014164940.
Maternal high-fat diet (HFD) during pregnancy and lactation induces depression- like phenotype and provokes myelin-related changes in rat offspring in the prefrontal cortex (PFCTX), which persist even to adulthood.
Due to the plasticity of the developing brain, it was decided to analyze whether depressionlike phenotype and myelin-related changes in the early lifetime induced by maternal HFD (60% energy from fat) could be reversed by the omega-3 fatty acid-enriched diet (Ω3D) given from the postweaning period until adulthood (63rd day of life) in offspring.
We analyzed the effect of post-weaning Ω3D on the depressive-like phenotype (assessed by the forced swimming test) and myelin-related changes (measured using RT-qPCR, ELISA, and immunofluorescence staining) in the PFCTX of adult offspring.
Ω3D reversed increased immobility time in adult offspring induced by maternal HFD, without affecting the animals' locomotor activity. Molecularly, Ω3D normalized the reduced expression levels of myelin-oligodendrocyte glycoprotein (MOG), as well as myelin and lymphocyte protein (MAL) in males and MOG in females in the PFCTX, changes initially induced by maternal HFD. Additionally, Ω3D normalized the quantity of oligodendrocyte precursor cells and mature oligodendrocytes in the prelimbic, infralimbic, and cingulate cortex in males, which were reduced following maternal HFD exposure. In females, the Ω3D effect was less pronounced, with normalization of oligodendrocyte precursors occurring only in the infralimbic cortex.
These findings suggest that Ω3D may play a significant role in correcting behavioral and neurobiological changes caused by adverse prenatal conditions.
孕期和哺乳期母体高脂饮食(HFD)会诱发大鼠后代出现抑郁样表型,并在前额叶皮质(PFCTX)引发与髓鞘相关的变化,这些变化甚至会持续到成年期。
由于发育中的大脑具有可塑性,因此决定分析母体HFD(脂肪提供60%的能量)在生命早期诱发的抑郁样表型和与髓鞘相关的变化,是否能通过在断奶后至成年期(出生后第63天)给后代喂食富含ω-3脂肪酸的饮食(Ω3D)得以逆转。
我们分析了断奶后Ω3D对成年后代PFCTX中抑郁样表型(通过强迫游泳试验评估)和与髓鞘相关的变化(使用RT-qPCR、ELISA和免疫荧光染色测量)的影响。
Ω3D逆转了母体HFD诱导的成年后代不动时间增加的情况,且不影响动物的运动活性。在分子水平上,Ω3D使PFCTX中雄性髓鞘少突胶质细胞糖蛋白(MOG)以及髓鞘和淋巴细胞蛋白(MAL)的表达水平降低恢复正常,雌性中MOG的表达水平降低也恢复正常,这些变化最初是由母体HFD诱导的。此外,Ω3D使雄性前边缘、边缘下和扣带回皮质中少突胶质前体细胞和成熟少突胶质细胞的数量恢复正常,母体HFD暴露后这些细胞数量减少。在雌性中,Ω3D的作用不太明显,仅在边缘下皮质中少突胶质前体细胞数量恢复正常。
这些发现表明,Ω3D可能在纠正不良产前条件引起的行为和神经生物学变化方面发挥重要作用。