Nobuyuki Karasawa

Soft-diet feeding decreases dopamine release and impairs aversion learning in Alzheimer model rats

To examine the effects of soft-diet feeding on the dopaminergic system in a model rat for Alzheimers disease (AD), we measured dopamine release in the hippocampus using a microdialysis approach and assessed learning ability and memory using step-through passive avoidance tests. Furthermore, we immunohistochemically examined the ventral tegmental area (VTA), which is the origin of hippocampal dopaminergic fibers using tyrosine hydroxylase (TH), a marker enzyme for the dopaminergic nervous system. Feeding a soft diet decreased dopamine release in the hippocampus and impaired learning ability and memory in AD model rats in comparison with rats fed a hard diet; however, TH-immunopositive profiles in the VTA seemed not to be notably different between rats fed a soft diet and those fed a hard diet. These observations suggest that soft-diet feeding enhances the impairment of learning ability and memory through the decline of dopamine release in the hippocampus in AD rats.

Tyrosine Hydroxylase (TH)- and Aromatic-L-Amino Acid Decarboxylase (AADC)-Immunoreactive Neurons of the Common Marmoset (Callithrix jacchus) Brain: An Immunohistochemical Analysis

From the perspective of comparative morphology, the distribution of non-monoaminergic neurons in the common marmoset (Callithrix jacchus) was investigated using an immunohistochemical method with specific antibodies to tyrosine hydroxylase (TH) and aromatic-L-amino acid decarboxylase (AADC). TH-immunoreactive (IR) neurons (but not AADC-IR) neurons were observed in the olfactory tubercle, preoptic suprachiasmatic nucleus, periventricular hypothalamic nucleus, arcuate nucleus, paraventricular nucleus, periaqueductal gray matter, medial longitudinal fasciculus, substantia nigra, and nucleus solitaris. In contrast, AADC-IR (but not TH-IR), small, oval and spindle-shaped neurons were sparsely distributed in the following areas: the hypothalamus from the anterior nucleus to the lateral nucleus, the dorsomedial nucleus, the dorsomedial area of the medial mammillary nucleus and the arcuate nucleus; the midbrain, including the stria medullaris and substantia nigra; and the medulla oblongata, including the dorsal area of the nucleus solitaris and the medullary reticular nucleus. The distribution of AADC-IR neurons was not as extensive in the marmoset as it is in rats. However, these neurons were located in the marmoset, but not the rat substantia nigra. Furthermore, AADC-IR neurons that are present in the human striatum were absent in that of the marmoset. The present results indicate that the distribution of non-monoaminergic neurons in the brain of the common marmoset is unique and different from that in humans and rodents.

Chewing under restraint stress inhibits the stress-induced suppression of cell birth in the dentate gyrus of aged SAMP8 mice

To investigate the mechanisms underlying impaired hippocampal function resulting from masticatory dysfunction, we examined the effects of the molarless condition on cell proliferation and the effect of the administration of metyrapone, which suppresses the stress-induced rise in plasma corticosterone levels, on cell proliferation in the hippocampal dentate gyrus (DG) of aged senescence-accelerated prone (SAMP8) mice. In addition, we examined whether chewing under restraint stress prevents the stress-induced suppression of cell proliferation. In aged mice, the molarless condition suppressed cell proliferation in the hippocampal DG. Vehicle-injected molarless mice had significantly higher plasma corticosterone levels than vehicle-injected control and metyrapone-injected molarless mice, in association with decreased cell proliferation in the hippocampal DG. Pretreatment with metyrapone inhibited the increase in plasma corticosterone levels induced by the bite-raised condition, and also attenuated the reduction in cell proliferation. Immobilization stress suppressed cell proliferation in the hippocampal DG, but chewing under restraint stress blocked the stress-induced suppression of cell proliferation in the DG. These results suggest that the morphologic deficits induced by the molarless condition in aged SAMP8 mice are a result of increased plasma corticosterone levels, and that chewing under restraint stress prevents the stress-induced suppression of cell birth in the DG.

Effects of occlusal disharmony on the cholinergic system in the septohippocampal tract of SAMP8 mice

Schizophrenia is a severe psychiatric disorder with a worldwide prevalence of about 1%. Multiple independent studies based on cytokine measurements indicate a shift from Th1-like to Th2-like immune reactivity. However, the molecular bases of the shift in immune cells observed in schizophrenic patients remain unclear. In order to determine molecular bases of the shift in helper T cells, and the involvement into the pathogenesis of schizophrenia, we developed a research system to evaluate comprehensive gene expression profiles of Th1 and Th2 cells using fluorescence-activated cell sorting and microarray technologies. After obtaining written informed consent following the IRB-approved protocol, peripheral blood lymphocytes from 18 patients with schizophrenia and 18 control subjects were collected by Ficoll differential centrifugation. Lymphocytes were stained with anti-CD4-FITC, CXCR3-APC, CCR45-PE. Th1 (CD4+/CXCR3+) and Th2 (CD4+/CCR4+) cell sorting experiments were performed using FACS Aria. Extracted total RNA sample from each cell was amplified and applied on Illumina Human-6v2 BeadChips to analyze global changes in genome-wide mRNA expression levels. FACSarray gene expression profiling determined 223 increased and 586 decreased genes in Th1 helper T cells, and 87 increased and 108 decreased genes in Th2 helper T cells from schizophrenic patients, compared to control subjects. Genes dysregulated in Th1 genes of schizophrenic patients contain zinc finger genes and biopolymer modification related genes. Genes dysregulated in Th2 genes of schizophrenic patients include telomere maintenance related genes and chromosomal protein coding genes. These genes may be relevant to the Th1/Th2 imbalance observed in schizophrenic patients, and the pathophysiology of the disease.

Occlusal disharmony reduces cell proliferation in the hippocampal dentate gyrus of SAMP8 mice

Schizophrenia is a severe psychiatric disorder with a worldwide prevalence of about 1%. Multiple independent studies based on cytokine measurements indicate a shift from Th1-like to Th2-like immune reactivity. However, the molecular bases of the shift in immune cells observed in schizophrenic patients remain unclear. In order to determine molecular bases of the shift in helper T cells, and the involvement into the pathogenesis of schizophrenia, we developed a research system to evaluate comprehensive gene expression profiles of Th1 and Th2 cells using fluorescence-activated cell sorting and microarray technologies. After obtaining written informed consent following the IRB-approved protocol, peripheral blood lymphocytes from 18 patients with schizophrenia and 18 control subjects were collected by Ficoll differential centrifugation. Lymphocytes were stained with anti-CD4-FITC, CXCR3-APC, CCR45-PE. Th1 (CD4+/CXCR3+) and Th2 (CD4+/CCR4+) cell sorting experiments were performed using FACS Aria. Extracted total RNA sample from each cell was amplified and applied on Illumina Human-6v2 BeadChips to analyze global changes in genome-wide mRNA expression levels. FACSarray gene expression profiling determined 223 increased and 586 decreased genes in Th1 helper T cells, and 87 increased and 108 decreased genes in Th2 helper T cells from schizophrenic patients, compared to control subjects. Genes dysregulated in Th1 genes of schizophrenic patients contain zinc finger genes and biopolymer modification related genes. Genes dysregulated in Th2 genes of schizophrenic patients include telomere maintenance related genes and chromosomal protein coding genes. These genes may be relevant to the Th1/Th2 imbalance observed in schizophrenic patients, and the pathophysiology of the disease.

Maternal chewing rescues stress-induced deterioration of learning-stimulated hippocampal neurogenesis in her beby

SC. Chewing significantly counteracted the stress-reduced number of the open-arm entries into the maze (2.9 ± 0.8 and 7.6 ± 0.8 times in ST and SC, respectively; n = 8 each; p < 0.01) to a level comparable to the control (4.2 ± 0.8 times; n = 9; p = 0.08). The extracellular concentration of dopamine, but not noradrenaline and serotonin, in the ventral hippocampus of the rats in SC was significantly higher than those in ST at the same post-stress time period (168 ± 15% and 250 ± 11% of baseline in ST and SC, respectively; n = 8 each; p < 0.01). The number of open-arm entries in ST and SC became comparable by administrating SCH23390 (1.9 ± 0.8 and 1.8 ± 0.5 times in ST and SC with drug treatment, respectively; n = 8 each; p = 0.89). Our results suggest that chewing activates the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiety-like behavior.

Occlusal disharmony reduces the activity of catecholaminergic system

In order to assess whether toothless (extracting the upper molar teeth) at an early period after eruption of teeth (early toothless) exerts greater effects on hippocampal aging processes than late toothless, morphological and behavioral studies were done in the SAMP8 mice. Not only early toothless enhanced age-dependent decline in learning ability in a water maze test, but also in more decreased the number of hippocampal neurons than those in the age-matched control condition. However, the effects of late toothless was not significant, when compared with those in the control condition. The data suggest that a long-lasting toothless condition may result in progressing aging processes in the hippocampus.