Funes Alejandrina, Ramirez Abraham I, Konjuh Cintia N, Rosso Silvana B, Cuesta Santiago, Pacchioni Alejandra M
Laboratorio de Toxicología Experimental, Departamento de Ciencias de los Alimentos y del Medioambiente, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Rosario, Santa Fe, S2002LRL, Argentina.
CONICET-Rosario, S2000EZP, Rosario, Santa Fe, Argentina.
J Mol Neurosci. 2025 May 27;75(2):70. doi: 10.1007/s12031-025-02341-8.
Adolescence is a key period of development when major cognitive and neurobiological changes occur. Results from our lab showed that 5 days of social isolation in adolescent rats led to molecular changes in the Wnt/β-catenin pathway and to higher cocaine responses during adulthood. We assessed whether 5 days of social isolation (SI) during adolescence would impact on β-catenin levels in the prefrontal cortex (PFC) and nucleus accumbens (NAcc) as well as on anxiety-like behaviors in a sex- and time-dependent manner. We also investigated the role of dopaminergic neurotransmission on that impact, by using repeated administration of a D2 antagonist. Male and female Wistar rats were socially isolated between postnatal day (PND)30 to 35 or kept in their home cages (non-isolated), while they were treated with sulpiride (100 mg/kg, ip) or vehicle. Anxiety-like behaviors and exploratory activity were estimated by the open field test at 24 h (PND36) or 9 days (PND44) after isolation. Then, they were euthanized at PND36 or PND45, and β-catenin levels were analyzed by Western blot in PFC and NAcc. Our findings show that a brief SI during adolescence leads to a long-term impact on both β-catenin levels (10 days, PND45) and anxiety-like behaviors (9 days, PND44) with a significant increase and decrease, respectively, in female rats. In contrast, male rats show a rapid decrease in β-catenin levels in the PFC with no changes in anxiety-like behaviors (24 h, PND36). These suggest that adolescent SI induces mostly long-term changes in female while short term changes in male rats. Moreover, these changes seem to be modulated by dopaminergic neurotransmission since a sulpiride treatment during isolation prevented them.
青春期是发生重大认知和神经生物学变化的关键发育时期。我们实验室的结果表明，青春期大鼠5天的社会隔离会导致Wnt/β-连环蛋白通路发生分子变化，并导致成年期对可卡因的反应增强。我们评估了青春期5天的社会隔离（SI）是否会以性别和时间依赖性方式影响前额叶皮质（PFC）和伏隔核（NAcc）中的β-连环蛋白水平以及焦虑样行为。我们还通过重复给予D2拮抗剂来研究多巴胺能神经传递在这种影响中的作用。雄性和雌性Wistar大鼠在出生后第（PND）30至35天期间进行社会隔离或饲养在其笼舍中（非隔离），同时用舒必利（100mg/kg，腹腔注射）或赋形剂进行处理。在隔离后24小时（PND36）或9天（PND44）通过旷场试验评估焦虑样行为和探索活动。然后，在PND36或PND45对它们实施安乐死，并通过蛋白质免疫印迹法分析PFC和NAcc中的β-连环蛋白水平。我们的研究结果表明，青春期短暂的社会隔离会对β-连环蛋白水平（10天，PND45）和焦虑样行为（9天，PND44）产生长期影响，雌性大鼠中β-连环蛋白水平显著增加，焦虑样行为显著减少。相比之下，雄性大鼠PFC中的β-连环蛋白水平迅速下降，焦虑样行为无变化（24小时，PND36）。这些结果表明，青春期社会隔离在雌性大鼠中主要诱导长期变化，而在雄性大鼠中诱导短期变化。此外，这些变化似乎受到多巴胺能神经传递的调节，因为隔离期间的舒必利治疗可预防这些变化。
