〔Abstract〕 ObjectiveTo investigate the impact of mandibular retrognathism on brain function in rats and its potential mechanisms. Method Male SD rats aged 3 to 4 weeks (w) were randomly divided into control group ( n=10) and mandible retrusion (MR) group ( n=30), with the MR group further divided into three subgroups: 1, 2, or 4 weeks, with 10 rats in each subgroup. The MR group used modified metal tubes, which were bonded to the lingual side of the maxillary incisors in rats, forcing the mandible to retract by 2 mm-2.5 mm, thereby achieving the goal of constructing a mandibular retrognathism model; the control group received no interventions. The effects of mandibular retraction on the spatial learning ability and memory ability of rats were explored by behavioral experiments such as Morris water maze, Y maze and new object recognition 1, 2, and 4 weeks after modeling, respectively. Hematoxylin-eosin (HE) and Nissl staining were employed to observe the histomorphological changes in CA1, CA3, and DG regions of hippocampal tissues; Immunohistochemistry was employed to detect the protein expression levels of tropomyosin receptor kinase B (TrkB) in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus. Western blot was used to assess the expression changes in the TrkB/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway in hippocampal tissue. Quantitative analysis of apoptosis-related proteins in the hippocampus, including Bcl-2-associated X protein (Bax), B-cell lymphoma-2 protein (Bcl-2), and Caspase-3, was conducted using qRT-PCR and Western blot. Results Behavioral experiments showed that rats in the MR group, especially the MR4 w group, were significantly weaker in learning and spatial memory than the control group, MR1 w, and MR2 w（ P＜0.05）. HE staining showed that pyramidal cells in the control group were arranged orderly with regular morphology. In contrast, the MR group exhibited a reduction in the number of cells in the hippocampal CA1, CA3, and dentate gyrus (DG) regions. The cells were sparsely and irregularly arranged, with nuclear condensation and enlarged cellular spaces. Nissl staining further demonstrated damage to the Nissl bodies in the MR group. Meanwhile, the TrkB/PI3K/AKT signaling pathway was activated in the MR group, and the expression of p-TrkB, PI3K, and p-AKT proteins was up-regulated ( P<0.05); Western blot and qRT-PCR indicated that MR up-regulated the expression of pro-apoptotic protein Bax, apoptotic effector protein Caspase-3 ( P<0.05), and inhibited the expression of anti-apoptotic protein Bcl-2 ( P<0.05). Conclusion Mandibular retraction impairs brain function and affects cognition and learning memory in rats. This may be achieved by regulating the TrkB/PI3K/AKT signaling pathway to induce apoptosis in hippocampal neurons.