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===Mastication and Cognitive Processes=== In recent years, mastication has been a topic of discussion about the maintenance and support effects of cognitive performance. An elegant study performed through <sub>f</sub>MR and positron emission tomography (PET) has shown that mastication leads to an increase in cortical blood flow and activates the additional somatosensory cortex, motor motor and insular, as well as the striatum, the thalamus, and the cerebellum. Mastication right before performing a cognitive task increases oxygen levels in the blood (BOLD of the fMRI signal) in the prefrontal cortex and the hippocampus, important structures involved in learning and memory, thereby improving the performance task.<ref>{{Cite book | autore = Yamada K | autore2 = Park H | autore3 = Sato S | autore4 = Onozuka M | autore5 = Kubo K | autore6 = Yamamoto T | titolo = Dynorphin-A immunoreactive terminals on the neuronal somata of rat mesencephalic trigeminalnucleus | url = | volume = | opera = Neurosci Lett | anno = 2008 | editore = Elsevier Ireland | città = | ISBN = | PMID = 18455871 | PMCID = | DOI = 10.1016/j.neulet.2008.04.030 | oaf = <!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref> Previous epidemiological studies have shown that a reduced number of residual teeth, incongruous use of prosthetics, and a limited development of the mandibular force are directly related to the development of dementia, further supporting the notion that mastication contributes to maintaining cognitive functions.<ref>{{Cite book | autore = Kondo K | autore2 = Niino M | autore3 = Shido K | titolo = Dementia. A case-control study of Alzheimer's disease in Japan - significance of life-styles | url = https://pubmed.ncbi.nlm.nih.gov/7866485/ | volume = | opera = | anno = 1994 | editore = | città = | ISBN = | PMID = 7866485 | PMCID = | DOI = 10.1159/000106741 | oaf = <!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref>. A recent study has provided further evidence in support of the interaction between masticatory processes, learning and memory, focusing on the function of the hippocampus that is essential for the formation of new memories<ref name="MFCF">{{Cite book | autore = Kubo KY | autore2 = Ichihashi Y | autore3 = Kurata C | autore4 = Iinuma M | autore5 = Mori D | autore6 = Katayama T | autore7 = Miyake H | autore8 = Fujiwara S | autore9 = Tamura Y | titolo = Masticatory function and cognitive function | url = https://www.jstage.jst.go.jp/article/ofaj/87/3/87_3_135/_article | volume = | opera = Okajimas Folia Anat Jpn | anno = 2010 | editore = | città = | ISBN = | PMID = 21174943 | PMCID = | DOI = 10.2535/ofaj.87.135 | oaf = yes<!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref>. An occlusal disharmony, such as loss of teeth and increases in the vertical occlusal dimension, causes bruxism or pain to the mastication muscles and temporomandibular disorders (TMDs)<ref>{{Cite book | autore = Christensen J | titolo = Effect of occlusion-raising procedures on the chewing system | url = | volume = | opera = Dent Pract Dent Rec | anno = 1970 | editore = | città = | ISBN = | PMID = 5266427 | PMCID = | DOI = | oaf = <!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref><ref name="ICHI2">{{Cite book | autore = Ichihashi Y | autore2 = Arakawa Y | autore3 = Iinuma M | autore4 = Tamura Y | autore5 = Kubo KY | autore6 = Iwaku F | autore7 = Sato Y | autore8 = Onozuka M | titolo = Occlusal disharmony attenuates glucocorticoid negative feedback in aged SAMP8 mice | url = | volume = | opera = Neurosci Lett | anno = 2007 | editore = | città = | ISBN = | PMID = 17928141 | PMCID = | DOI = 10.1016/j.neulet.2007.09.020 | oaf = <!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref>. Hence, to describe the impaired function of the hippocampus in a reduced situation or abnorme masticatory function, the authors employed an animal model (mice) called ‘Molarless Senescence-Accelerated Prone’ (SAMP8) in order to make a parallelism on man. In SAMP8 mice, to which the occlusion was modified, increasing the occlusal vertical dimension of about 0.1 mm with dental materials showed that the occlusal disharmony disrupts learning and memory. These animals showed an age-dependent deficit in space learning at Morris’s water. <ref>{{Cite book | autore = Arakawa Y | autore2 = Ichihashi Y | autore3 = Iinuma M | autore4 = Tamura Y | autore5 = Iwaku F | autore6 = Kubo KY | titolo = Duration-dependent effects of the bite-raised condition on hippocampal function in SAMP8 mice | url = https://www.jstage.jst.go.jp/article/ofaj/84/3/84_3_115/_pdf/-char/en | volume = | opera = Okajimas Folia Anat Jpn | anno = 2007 | editore = | città = | ISBN = | PMID = 18186225 | PMCID = | DOI = 10.2535/ofaj.84.115 | oaf = yes<!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref><ref name="ODIS">{{Cite book | autore = Kubo KY | autore2 = Yamada Y | autore3 = Iinuma M | autore4 = Iwaku F | autore5 = Tamura Y | autore6 = Watanabe K | autore7 = Nakamura H | autore8 = Onozuka M | titolo = Occlusal disharmony induces spatial memory impairment and hippocampal neuron degeneration via stress in SAMP8 mice | url = | volume = | opera = Neurosci Lett | anno = 2007 | editore = Elsevier Ireland | città = | ISBN = | PMID = 17207572 | PMCID = | DOI = 10.1016/j.neulet.2006.12.020 | oaf = <!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref>Increasing the vertical dimension of the bite in SAMP8 mice decreases the number of pyramidal cells<ref name="ODIS" /> and the numbers of their dendritic spines.<ref>{{Cite book | autore = Kubo KY | autore2 = Kojo A | autore3 = Yamamoto T | autore4 = Onozuka M | titolo = The bite-raised condition in aged SAMP8 mice induces dendritic spine changes in the hippocampal region | url = | volume = | opera = Neurosci Lett | anno = 2008 | editore = | città = | ISBN = | PMID = 18614288 | PMCID = | DOI = 10.1016/j.neulet.2008.05.027 | oaf = <!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref> It also increases the hypertrophy and hyperplasia fibrillar protein acid in astrocytes in the regions of the CA1 and CA3 hippocampus.<ref>{{Cite book | autore = Ichihashi Y | autore2 = Saito N | autore3 = Arakawa Y | autore4 = Kurata C | autore5 = Iinuma M | autore6 = Tamura Y | autore7 = Iwaku F | autore8 = Kubo KY | titolo = The bite-raised condition in aged SAMP8 mice reduces the expression of glucocorticoid receptors in the dorsal and ventral hippocampus | url = https://www.jstage.jst.go.jp/article/ofaj/84/4/84_4_137/_pdf/-char/en | volume = | opera = Okajimas Folia Anat Jpn | anno = 2008 | editore = | città = | ISBN = | PMID = 18464530 | PMCID = | DOI = 10.2535/ofaj.84.137 | oaf = YES<!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref>. In rodents and monkeys, occlusal disharmonies induced through an increase in the vertical dimension with acrylic increases on the incisors<ref name="ARESO">{{Cite book | autore = Areso MP | autore2 = Giralt MT | autore3 = Sainz B | autore4 = Prieto M | autore5 = García-Vallejo P | autore6 = Gómez FM | titolo = Occlusal disharmonies modulate central catecholaminergic activity in the rat | url = https://pubmed.ncbi.nlm.nih.gov/10371243/ | volume = | opera = J Dent Res | anno = 1999 | editore = | città = | ISBN = | PMID = 10371243 | PMCID = | DOI = 10.1177/00220345990780060301 | oaf = <!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref><ref>{{Cite book | autore = Yoshihara T | autore2 = Matsumoto Y | autore3 = Ogura T | titolo = Occlusal disharmony affects plasma corticosterone and hypothalamic noradrenaline release in rats | url = | volume = | opera = J Dent Res | anno = 2001 | editore = | città = | ISBN = | PMID = 11808768 | PMCID = | DOI = 10.1177/00220345010800121301 | oaf = <!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref> or the insertion of bite-plane in the jaw are associated with increased urinary cortisol levels and elevated plasma levels of corticosterone, suggesting that occlusal disharmony is also a source of stress. In support of this notion, SAMP8 mice with learning deficits show a marked increase in the plasma levels of corticosterone<ref name="ICHI2" /> and subregulation of GR and GRmRNA of the hippocampus. The occlusal disharmony also affects catecholaminergic activity. Alternating the closure of the bite by inserting an acrylic bite-plane on the lower incisors leads to an increase in levels of dopamine and noradrenaline in the hypothalamus and the frontal cortex<ref name="ARESO" /><ref>{{Cite book | autore = Gómez FM | autore2 = Areso MP | autore3 = Giralt MT | autore4 = Sainz B | autore5 = García-Vallejo P | titolo = Effects of dopaminergic drugs, occlusal disharmonies, and chronic stress on non-functional masticatory activity in the rat, assessed by incisal attrition | url = https://pubmed.ncbi.nlm.nih.gov/9649174/ | volume = | opera = J Dent Res | anno = 1998 | editore = | città = | ISBN = | PMID = 9649174 | PMCID = | DOI = 10.1177/00220345980770061001 | oaf = <!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref>, and decreases in thyroxinaydroxylase, GTP cyclohydrochloride, and immunoreactive serotonin in the cerebral cortex and the caudate nucleus, in the nigra substance, in the locus ceruleus, and in the dorsal raphe nucleus, which are similar to chronic stress-induced changes.<ref>{{Cite book | autore = Feldman S | autore2 = Weidenfeld J | titolo = Glucocorticoid receptor antagonists in the hippocampus modify the negative feedback following neural stimuli | url = | volume = | opera = Brain Res | anno = 1999 | editore = Elsevier Science B.V. | città = | ISBN = | PMID = 10064785 | PMCID = | DOI = 10.1016/s0006-8993(99)01054-9 | oaf = <!-- qualsiasi valore --> | LCCN = | OCLC = }}</ref> These changes in the catecolaminergic and serotonergic systems, induced by occlusal disharmonies, clearly affect the innervation of the hippocampus. The conditions of increasing the vertical dimension alter neurogenesis and lead to apoptosis in the ippocampal gyrus by decreasing the expression of the ippocampal brain derived from neurotrophic factors: all this could contribute to the changes in observed learning in animals with occlusal disharmony.<ref name="MFCF" />
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