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  }}</ref><ref name=":0">Kubo, K.Y., et al., ''Occlusal disharmony induces spatial memory impairment and hippocampal neuron degeneration via stress in SAMP8 mice.'' Neurosci Lett, 2007. 414(2): p. 188-91 https://www.ncbi.nlm.nih.gov/pubmed/?term=Occlusal+disharmony+induces+spatial+memory+impairment+and+hippocampal+neuron+degeneration+via+stress+in+SAMP8+mice.+Neurosci+Lett%2C+2007</ref>  

  }}</ref><ref name="ODIS">{{Cite book

| autore = Kubo KY

| autore6 = Watanabe K

| titolo = Occlusal disharmony induces spatial memory impairment and hippocampal neuron degeneration via stress in SAMP8 mice

| opera = Neurosci Lett

| anno = 2007

| DOI = 10.1016/j.neulet.2006.12.020

| OCLC =  

}}</ref>  

Increasing the vertical dimension of the bite in SAMP8 mice decreases the number of pyramidal cells<ref name=":0" /> and the numbers of their dendritic spines.<ref>Kubo, K.Y., et al., ''The bite-raised condition in aged SAMP8 mice induces dendritic spine changes in the hippocampal region.'' Neurosci Lett, 2008. 441(2): p. 141-4. https://www.ncbi.nlm.nih.gov/pubmed/?term=The+bite-raised+condition+in+aged+SAMP8+mice+induces+dendritic+spine+changes+in+the+hippocampal+region.+Neurosci+Lett%2C+2008.</ref> It also increases the hypertrophy and hyperplasia fibrillar protein acid in astrocytes in the regions of the CA1 and CA3 hippocampus. <ref>Ichihashi, Y., et al., ''The bite-raised condition in aged SAMP8 mice reduces the expression of glucocorticoid receptors in the dorsal and ventral hippocampus.'' Okajimas Folia Anat Jpn, 2008. 84(4): p. 137-42. https://www.ncbi.nlm.nih.gov/pubmed/?term=The+bite-raised+condition+in+aged+SAMP8+mice+reduces+the+expression+of+glucocorticoid+receptors+in+the+dorsal+and+ventral+hippocampus</ref>. In rodents and monkeys, occlusal disharmonies induced through an increase in the vertical dimension with acrylic increases on the incisors <ref name=":3">Areso, M.P., et al., ''Occlusal disharmonies modulate central catecholaminergic activity in the rat.'' J Dent Res, 1999. 78(6): p. 1204-13. https://www.ncbi.nlm.nih.gov/pubmed/?term=%2C+Occlusal+disharmonies+modulate+central+catecholaminergic+activity+in+the+rat.+J+Dent+Res%2C+1999</ref><ref>Yoshihara, T., Y. Matsumoto, and T. Ogura, ''Occlusal disharmony affects plasma corticosterone and hypothalamic noradrenaline release in rats.'' J Dent Res, 2001. 80(12): p. 2089-92. https://www.ncbi.nlm.nih.gov/pubmed/?term=Occlusal+disharmony+affects+plasma+corticosterone+and+hypothalamic+noradrenaline+release+in+rats.+J+Dent+Res%2C+2001</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.

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>Kubo, K.Y., et al., ''The bite-raised condition in aged SAMP8 mice induces dendritic spine changes in the hippocampal region.'' Neurosci Lett, 2008. 441(2): p. 141-4. https://www.ncbi.nlm.nih.gov/pubmed/?term=The+bite-raised+condition+in+aged+SAMP8+mice+induces+dendritic+spine+changes+in+the+hippocampal+region.+Neurosci+Lett%2C+2008.</ref> It also increases the hypertrophy and hyperplasia fibrillar protein acid in astrocytes in the regions of the CA1 and CA3 hippocampus. <ref>Ichihashi, Y., et al., ''The bite-raised condition in aged SAMP8 mice reduces the expression of glucocorticoid receptors in the dorsal and ventral hippocampus.'' Okajimas Folia Anat Jpn, 2008. 84(4): p. 137-42. https://www.ncbi.nlm.nih.gov/pubmed/?term=The+bite-raised+condition+in+aged+SAMP8+mice+reduces+the+expression+of+glucocorticoid+receptors+in+the+dorsal+and+ventral+hippocampus</ref>. In rodents and monkeys, occlusal disharmonies induced through an increase in the vertical dimension with acrylic increases on the incisors <ref name=":3">Areso, M.P., et al., ''Occlusal disharmonies modulate central catecholaminergic activity in the rat.'' J Dent Res, 1999. 78(6): p. 1204-13. https://www.ncbi.nlm.nih.gov/pubmed/?term=%2C+Occlusal+disharmonies+modulate+central+catecholaminergic+activity+in+the+rat.+J+Dent+Res%2C+1999</ref><ref>Yoshihara, T., Y. Matsumoto, and T. Ogura, ''Occlusal disharmony affects plasma corticosterone and hypothalamic noradrenaline release in rats.'' J Dent Res, 2001. 80(12): p. 2089-92. https://www.ncbi.nlm.nih.gov/pubmed/?term=Occlusal+disharmony+affects+plasma+corticosterone+and+hypothalamic+noradrenaline+release+in+rats.+J+Dent+Res%2C+2001</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=":2" /> 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=":3" /><ref>Gomez, F.M., et al., ''Effects of dopaminergic drugs, occlusal disharmonies, and chronic stress on non-functional masticatory activity in the rat, assessed by incisal attrition.'' J Dent Res, 1998. '''77'''(6): p. 1454-64. https://www.ncbi.nlm.nih.gov/pubmed/?term=Effects+of+dopaminergic+drugs%2C+occlusal+disharmonies%2C+and+chronic+stress+on+non-functional+masticatory+activity+in+the+rat%2C+assessed+by+incisal+attrition.+J+Dent+Res%2C+1998</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>Feldman, S. and J. Weidenfeld, ''Glucocorticoid receptor antagonists in the hippocampus modify the negative feedback following neural stimuli.'' Brain Res, 1999. 821(1): p. 33-7. https://www.ncbi.nlm.nih.gov/pubmed/?term=Effects+of+dopaminergic+drugs%2C+occlusal+disharmonies%2C+and+chronic+stress+on+non-functional+masticatory+activity+in+the+rat%2C+assessed+by+incisal+attrition.+J+Dent+Res%2C+1998</ref> hese 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" />  

In support of this notion, SAMP8 mice with learning deficits show a marked increase in the plasma levels of corticosterone <ref name=":2" /> 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=":3" /><ref>Gomez, F.M., et al., ''Effects of dopaminergic drugs, occlusal disharmonies, and chronic stress on non-functional masticatory activity in the rat, assessed by incisal attrition.'' J Dent Res, 1998. '''77'''(6): p. 1454-64. https://www.ncbi.nlm.nih.gov/pubmed/?term=Effects+of+dopaminergic+drugs%2C+occlusal+disharmonies%2C+and+chronic+stress+on+non-functional+masticatory+activity+in+the+rat%2C+assessed+by+incisal+attrition.+J+Dent+Res%2C+1998</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>Feldman, S. and J. Weidenfeld, ''Glucocorticoid receptor antagonists in the hippocampus modify the negative feedback following neural stimuli.'' Brain Res, 1999. 821(1): p. 33-7. https://www.ncbi.nlm.nih.gov/pubmed/?term=Effects+of+dopaminergic+drugs%2C+occlusal+disharmonies%2C+and+chronic+stress+on+non-functional+masticatory+activity+in+the+rat%2C+assessed+by+incisal+attrition.+J+Dent+Res%2C+1998</ref> hese 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" />