Chewing Prevents Stress-Induced Hippocampal LTD Formation and Anxiety-Related Behaviors: A Possible Role of the Dopaminergic System

Abstract

The present study examined the effects of chewing on stress-induced long-term depression (LTD) and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior.

Revisiting the link between cognitive decline and masticatory dysfunction

“…In general, these studies have supported the hypothesis that cognitive decline is associated with masticatory dysfunction. These studies have demonstrated that cognitive decline is related to cellular and neurochemical change in the hippocampus, including decreased cellular proliferation [ 47 , 48 , 50 ], decreased levels of brain-derived neurotrophic factor [ 44 , 47 , 59 ], as well as increased nitrous oxide levels [ 55 ] and extracellular dopamine levels [ 52 ]. These findings suggested that the hippocampus-dependent deficits in learning and memory may contribute to the association between cognitive decline and masticatory dysfunction [ 10 ].…”

“…These findings suggested that the hippocampus-dependent deficits in learning and memory may contribute to the association between cognitive decline and masticatory dysfunction [ 10 ]. Importantly, using animal models, researchers were able to investigate the interactional effect between masticatory dysfunction and other factors, such as the type of diet [ 46 , 59 ], environmental stimuli [ 47 ], and stress [ 52 ]. These factors can partially ameliorate the cognitive deficits induced by masticatory dysfunction [ 46 , 47 ].…”

“…Language: English 3. Publication date: 2012.10.15–2017.10.15 Reference Strain/Experimental manipulation Behavioral findings Cellular /neurochemical findings Fukushima-Nakayama et al 2017 [ 44 ] C57BL/6 J mice/Normal (N) or solid (S) diet Passive avoidance test (−) and Object location test (−) in S group Hippocampal neurons, neurogenesis, neuronal activity (−), BDNF expression (−) in S group Kubo et al 2017 [ 48 ] SAMP8 mice/Tooth loss soon after tooth eruption Morris water maze (−) Cell proliferation/cell survival in DG (−) Synaptophysin expression in HIP (−) Newborn cell differentiation in DG (X) Avivi-Arber et al 2016 [ 43 ] 7 strains of female mice/Molar extraction Regional and voxel-wise volumes of cortical brain regions (−) and subcortical, sensorimotor, temporal limbic regions (+) Takeda et al 2016 [ 59 ] C57BL/6 J mice/Molar extraction (E) and powder (P) or solid (S) diet Step-through passive avoidance test (−) for E/S and E/P groups 16 weeks later BDNF-related mRNA in HIP (−) for E/S and E/P groups 16 weeks later Oue et al 2016 [ 53 ] APP transgenic mice/Molar extraction Step-through passive avoidance test (X) Amount of Aβ and number of pyramidal cells in HIP (X) Kondo et al 2016 [ 47 ] SAMP8 mice/Molar extraction (E) or intact (I) and standard (S) or enriched (R) environment Morris water maze (−) in E group Proliferation and survival of newborn cells in DG (−) and BDNF levels in HIP (−) in E group The effect was attenuated in E/R group Kida et al 2015 [ 46 ] Tooth extraction (E) and zinc-deficient (ZD) or zinc-sufficient (ZS) Spatial memory (−) in E/ZD group; recovered in E/ZS group Astrocytic density in CA1 (+) in ZD group Pang et al 2015 [ 55 ] KM mice/Molar extraction Morris water maze (−) Levels of NO and inducible nitric oxide synthase in HIP (+) Ono et al 2015 [ 52 ] Stress condition (S), stress with voluntary chewing condition (SC), and control condition (C) Open-Field Test and Elevated Plus M...…”

“…As revealed by animal research, the effect of masticatory dysfunction on cognitive decline may interact with the nutritional [ 46 , 59 ] and mental condition of the organism [ 47 , 52 ]. Notably, these factors are associated with the physical fitness of the elderly, and the interactional effect of these factors on cognitive decline should be considered.…”

Headache Attributed to Obsessive Compulsive Disorder of Mastication

“…Some studies showed that chewing gum was associated with lower levels of perceived stress, such as anxiety and depression [2,3]. An experiment in rats found that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior [4]. But hyperactivity of musculi masticari can be the cause of headache [5,6].…”