Crushing and grinding food by teeth, the process as known mastication has important roles in receiving food, digesting food, and maintaining general health (H. Chen, Iinuma, Onozuka, & Kubo, 2015; Kubo, Iinuma, & Chen, 2015; Ono, Yamamoto, KUBO, & Onozuka, 2010). Masticatory disorders caused by tooth loss, periodontitis, and the improper vertical dimension of the crown affect life quality (Azuma et al., 2017, Proietti et al., 2011). Also, learning and memory impairment is the largest growing health problem that affects the quality of life (Bardestani et al., 2021, Ebrahimpour et al., 2020). Studies done on both humans and animals have publicized that tooth loss is a supposed cognitive dysfunction risk factor (Andoh et al., 2009; C.-K. Chen, Wu, & Chang, 2017; Goto & Leung, 2019; Lin, 2018; Okamoto et al., 2010; Oue et al., 2013). Tooth shortening (Ebrahimpour, Esmaeili, Esmaeili, Sattari, & Forouzandeh Hafshejani, 2021), chewing stimulation disorder (Weijenberg, Scherder, & Lobbezoo, 2011), malnutrition (Ikebe et al., 2018), periodontal disease-induced inflammatory molecules and bacterial products (Watts, Crimmins, & Gatz, 2008), oral sensory-motor dysfunction (De Cicco et al., 2016), and mental stress (Ono et al., 2010, Sakatani et al., 2013) are possible mechanisms explaining this phenomenon.

Sensory input associated with the masticatory muscles, periodontal ligament, and temporomandibular joint (TMJ) facilitates neurotransmission in the CNS (Schmid, Simons, & Schnitzler, 2003). Data that is now available suggests that oral dysfunction may be a risk factor for mental decline (Daisuke Ekuni et al., 2013; D Ekuni et al., 2011; Okimoto, 1991; Onozuka et al., 1999; Sakatani et al., 2013). Most likely, teeth loss and malocclusion lead to a reduction in sensory input to the brain via receptors related to mastication and jaw movements (Tonsekar et al., 2017, Tsutsui et al., 2007). Mastication might enhance cognitive functions including awareness, intelligence, quickness, attentiveness, and reaction time (Hirano & Onozuka, 2015). Mastication preserves the function of cognition in the hippocampus (Ono et al., 2010). It furthermore influences the development of the brain and its locomotor function (Hasegawa et al., 2007, Luo et al., 2019).

Teeth loss could lead to insignificant cognitive disorder, dementia, and possibly AD. Various investigations have indicated a connection between tooth loss and cognitive performance, but the molecular mechanisms are not clear. We previously showed an association between memory impairment and tooth shortening (Ebrahimpour et al., 2021). Amyloid-beta (Aβ) plays an essential role in the loss of neurons and cognitive dysfunction in AD (Hardy & Allsop, 1991). A study showed that periodontitis increased the Aβ peptide levels in serum (Leira et al., 2019). Additionally, studies have demonstrated the importance of the BACE1/AbPP, BDNF/TrkB, and Bax/Bcl-2 signaling pathways in learning and memory impairment (Ebrahimpour et al., 2020, Gao et al., 2022, Ko et al., 2018, Sun et al., 2021). However, the molecular mechanisms regarding tooth loss, especially tooth shortening, are now well understood. Numerous molecular pathways are probably involved. Considering the importance of signaling pathways BACE1/AbPP, BDNF/TrkB, and Bax/Bcl-2, the aim of our study is to investigate the effect of molar tooth shortening on the mRNA expression of these genes at the mRNA level in the hippocampus of male rats.