Ribeiro Inês, Silveira-Rosa Tiago, Martins-Macedo Joana, Marques-Ferraz Luísa, Dourado Ana Rita, Martins-Ferreira Gonçalo, Farrugia Fanny, Rodrigues Ana João, Abrous Djoher Nora, Alves Nuno Dinis, Patrício Patrícia, Pinto Luisa
Life and Health Sciences Research Institute (ICVS), School of Medicine, Univ of Minho, Braga, Portugal.
ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal.
Neurobiol Stress. 2025 Jul 7;37:100743. doi: 10.1016/j.ynstr.2025.100743. eCollection 2025 Jul.
Hippocampal Adult-Born neurons (hABNs) play a critical role in maintaining brain homeostasis, exhibiting unique properties during their maturation. The absence of hABNs impacts surrounding neuronal networks, but the mechanisms are not fully understood. In this study, we examined how perturbations to adult hippocampal cytogenesis affect the neuronal inputs to adult-born and mature neurons in the dentate gyrus. In particular, we analyzed connectivity changes in GFAP-Tk transgenic rats with ablated neurogenesis, and in unpredictable Chronic Mild Stress (uCMS) rats with reduced neurogenesis, with a focus on sex-differences in stress-affected hABNs. Additionally, we evaluated the action of the antidepressant fluoxetine on brain connectivity. Using a virus-mediated retrograde tracing approach, we quantified synaptic inputs to mature neurons and hABNs. Our findings reveal significant impairments in both intra- and extra-hippocampal connectivity following disruptions in cytogenesis, providing new insights into hippocampal network dynamics in the context of cytogenetic impairment, depression, and therapeutic interventions.
海马体成年新生神经元（hABNs）在维持脑内稳态中发挥关键作用，在其成熟过程中表现出独特特性。hABNs的缺失会影响周围神经网络，但其机制尚未完全明确。在本研究中，我们探究了成年海马体细胞生成的扰动如何影响齿状回中成年新生神经元和成熟神经元的神经输入。具体而言，我们分析了神经发生被消融的GFAP-Tk转基因大鼠以及神经发生减少的不可预测慢性轻度应激（uCMS）大鼠的连接性变化，重点关注应激影响的hABNs中的性别差异。此外，我们评估了抗抑郁药氟西汀对脑连接性的作用。使用病毒介导的逆行追踪方法，我们量化了成熟神经元和hABNs的突触输入。我们的研究结果揭示了细胞生成中断后海马体内外连接性均出现显著损伤，为细胞遗传学损伤、抑郁症及治疗干预背景下的海马体网络动力学提供了新见解。
