|Shozo Jinno||Last modified date：2022.07.12|
Professor / Department of Medicine and Bioregulatory Science / Department of Basic Medicine / Faculty of Medical Sciences
Unauthorized reprint of the contents of this database is prohibited.
|Shozo Jinno||Last modified date：2022.07.12|
|1.||Risako Fujikawa, Jun Yamada, Kyoko M Iinuma, Shozo Jinno, Phytoestrogen genistein modulates neuron-microglia signaling in a mouse model of chronic social defeat stress., Neuropharmacology, 10.1016/j.neuropharm.2021.108941, 206, 108941-108941, 2022.03, Microglia, resident immune cells in the brain, are shown to mediate the crosstalk between psychological stress and depression. Interestingly, increasing evidence indicates that sex hormones, particularly estrogen, are involved in the regulation of immune system. In this study, we aimed to understand the potential effects of chronic social defeat stress (CSDS) and genistein (GEN), an estrogenic compound of the plant origin, on neuron-microglia interactions in the mouse hippocampus. The time spent in the avoidance zone in the social interaction test was increased by CSDS 1 day after the exposure, while the avoidance behavior returned to control levels 14 days after the CSDS exposure. Similar results were obtained from the elevated plus-maze test. However, the immobility time in the forced swim test was increased by CSDS 14 days after the exposure, and the depression-related behavior was in part alleviated by GEN. The numerical densities of microglia in the hippocampus were increased by CSDS, and they were decreased by GEN. The voxel densities of synaptic structures and synaptic puncta colocalized with microglia were decreased by CSDS, and they were increased by GEN. Neither CSDS nor GEN affected the gene expressions of major pro-inflammatory cytokines. Conversely, the expression levels of genes related to neurotrophic factors were decreased by CSDS, and they were partially reversed by GEN. These findings show that GEN may in part alleviate stress-related symptoms, and the effects of GEN may be associated with the modulation of neuron-microglia signaling via chemokines and neurotrophic factors in the hippocampus..|
|2.||Tomohiro Ohgomori, Shozo Jinno, Signal Transducer and Activator of Transcription 3 Activation in Hippocampal Neural Stem Cells and Cognitive Deficits in Mice Following Short-term Cuprizone Exposure., Neuroscience, 10.1016/j.neuroscience.2021.07.031, 472, 90-102, 2021.09, Recent studies have emphasized that adult hippocampal neurogenesis impairment may be associated with cognitive problems. Because cuprizone (CPZ), a copper-chelating reagent, was shown to decrease the production of new neurons, we aimed to further understand the involvement of adult hippocampal neurogenesis impairment in cognitive function by using a short-term (2-week) CPZ exposure paradigm. The CPZ-fed mice showed cognitive deficits, i.e., impaired sensorimotor gating and reduced social novelty preference, compared to normal-fed mice. Although a long-term (e.g., 5-week) CPZ exposure paradigm was found to cause demyelination, we encountered that the labeling for myelin in the hippocampus was unaffected by 2-week CPZ exposure. The densities of neuronal progenitor cells (NPCs) and newborn granule cells (NGCs) were lower in CPZ-fed mice than in normal-fed mice, while those of neural stem cells (NSCs) were comparable between groups. We then examined whether short-term CPZ exposure might induce activation of signal transducer and activator of transcription 3 (STAT3), which plays a major role in cytokine receptor signaling. The densities of phosphorylated STAT3-positive (pSTAT3+) NSCs were higher in CPZ-fed mice than in normal-fed mice, while those of pSTAT3+ NPCs/NGCs were very low in both groups. Interestingly, the densities of bromodeoxyuridine-positive (BrdU+) NSCs were higher in CPZ-fed mice than in normal-fed mice 2 weeks after BrdU injection, while those of BrdU+ NPCs/NGCs were lower in CPZ-fed mice than in normal-fed mice. These findings suggest that short-term CPZ exposure inhibits differentiation of NSCs into NPCs via activation of STAT3, which may in part underlie cognitive deficits..|
|3.||Tomohiro Ohgomori, Kyoko Iinuma, Jun Yamada, Shozo Jinno, A unique subtype of ramified microglia associated with synapses in the rat hippocampus., The European journal of neuroscience, 10.1111/ejn.15330, 54, 3, 4740-4754, 2021.08, To date, a number of studies have reported the heterogeneity of activated microglia. However, there is increasing evidence suggests that ramified, so-called resting, microglia may also be heterogeneous, and they may play diverse roles in normal brain homeostasis. Here, we found that both 5D4 keratan sulfate epitope-positive (5D4+ ) and 5D4-negative (5D4- ) microglia coexisted in the hippocampus of normal rats, while all microglia were negative for the 5D4 epitope in the hippocampus of normal mice. We thus aimed to determine the potential heterogeneity of microglia related to the 5D4 epitope in the normal rat hippocampus. The optical disector analysis showed that the densities of 5D4+ microglia were higher in the stratum oriens of the CA3 region than in other layers and regions. Although both 5D4+ and 5D4- microglia exhibited a ramified morphology, the three-dimensional reconstruction analysis showed that the node numbers, end numbers, and complexity of processes were higher in 5D4+ than in 5D4- microglia. The linear discriminant analysis showed that 5D4+ and 5D4- microglia can be classified into distinct morphometric subtypes. The ratios of contact between synaptic boutons and microglial processes were higher in 5D4+ than in 5D4- microglia. The gene expressions of pro-inflammatory cytokine interleukin-1β and purinergic receptor P2Y12 (P2Y12 R) were higher in 5D4+ than in 5D4- microglia. Together, these results indicate that at least two different subtypes of ramified microglia coexist in the normal rat hippocampus and also suggest that 5D4+ microglia may represent a unique subtype associated with synapses..|
|4.||Jun Yamada, Chihiro Sato, Kohtarou Konno, Masahiko Watanabe, Shozo Jinno, PSA-NCAM Colocalized with Cholecystokinin-Expressing Cells in the Hippocampus Is Involved in Mediating Antidepressant Efficacy, The Journal of Neuroscience, 10.1523/jneurosci.1779-19.2019, 40, 4, 825-842, 2020.01, The extracellular glycan polysialic acid linked to neural cell adhesion molecule (PSA-NCAM) is principally expressed in the developing brain and the adult neurogenic regions. Although colocalization of PSA-NCAM with cholecystokinin (CCK) was found in the adult brain, the role of PSA-NCAM remains unclear. In this study, we aimed to elucidate the functional significance of PSA-NCAM in the CA1 region of the male mouse hippocampus. Combined fluorescence in situ hybridization and immunohistochemistry showed that few vesicular glutamate transporter 3-negative/CCK-positive (VGluT3-/CCK+) cells were colocalized with PSA-NCAM, but most of the VGluT3+/CCK+ cells were colocalized with PSA-NCAM. The somata of PSA-NCAM+/CCK+ cells were highly innervated by serotonergic boutons than those of PSA-NCAM-/CCK+ cells. The expression ratios of 5-HT3A receptors and p11, a serotonin receptor-interacting protein, were higher in PSA-NCAM+/CCK+ cells than in PSA-NCAM-/CCK+ cells. Pharmacological digestion of PSA-NCAM impaired the efficacy of antidepressant fluoxetine (FLX), a selective serotonin reuptake inhibitor, but not the efficacy of benzodiazepine anxiolytic diazepam. A Western blot showed that restraint stress decreased the expressions of p11 and mature brain-derived neurotrophic factor (BDNF), and FLX increased them. Interestingly, the FLX-induced elevation of expression of p11, but not mature BDNF, was impaired by the digestion of PSA-NCAM. Quantitative reverse transcription-polymerase chain reaction showed that restraint stress reduced the expression of polysialyltransferase ST8Sia IV and FLX elevated it. Collectively, PSA-NCAM colocalized with VGluT3+/CCK+ cells in the CA1 region of the hippocampus may play a unique role in the regulation of antidepressant efficacy via the serotonergic pathway.SIGNIFICANCE STATEMENT Polysialic acid (PSA) is composed of eight or more α2,8-linked sialic acids. Here, we examined the functional significance of polysialic acid linked to the neural cell adhesion molecule (PSA-NCAM) in the adult mouse hippocampus. Few vesicular glutamate transporter 3-negative/cholecystokinin-positive (VGluT3-/CCK+) cells were colocalized with PSA-NCAM, but most of the VGluT3+/CCK+ cells were colocalized with PSA-NCAM. The expression ratios of 5-HT3A receptors and p11, a serotonin receptor-interacting protein, were higher in PSA-NCAM+/CCK+ cells than in PSA-NCAM-/CCK+ cells. The efficacy of antidepressants, but not anxiolytics, was impaired by the digestion of PSA-NCAM. The antidepressant-induced increase in p11 expression was inhibited following PSA-NCAM digestion. We hence hypothesize that PSA-NCAM colocalized with VGluT3+/CCK+ cells may play a unique role in regulating antidepressant efficacy..|
|5.||[Functional differentiation along the longitudinal axis of the hippocampus, with reference to the neuronal circuits].
|6.||[Establishment of new research fundamentals in neuroscience by stereology]..|
|7.||S Jinno, T Kosaka, Colocalization of parvalbumin and somatostatin-like immunoreactivity in the mouse hippocampus: Quantitative analysis with optical disector, The Journal of Comparative Neurology, 428, 3, 377-388, 2000.12, The colocalization of parvalbumin (PV) and somatostatin (SS)-like immunoreactivity was studied quantitatively in the mouse hippocampus, with particular reference to their areal and dorsoventral differences. The optical disector method was applied by using a confocal laser scanning microscope with immunofluorescent double-labeling. In the present study, we found a particular subpopulation of hippocampal nonprincipal neurons that contained both PV and SS-like immunoreactivity, i.e., PV-immunoreactive (IR)/SS-like immunoreactive (LIR) neurons. In the CA1 region, PV-IR/SS-LIR, neurons were restricted to the stratum oriens (SO). In the CA3 region, they were scattered in the SO, stratum pyramidale (SP), and stratum radiatum (SR). However, they were rarely seen in the dentate gyrus (DG). The proportion of PV-IR/SS-LIR neurons in the PV-IR neurons or SS-LIR neurons was about 10% in the CA1 region, 15-30% in the CA3 region, 0-5% in the DG, and 10-20% in total. Laminar analysis revealed that the proportions of PV-IR/SS-LIR neurons in the PV-IR neurons were high in the SO (about 25%) of the CA1 region, and in the SO (about 50%) and SR (30-45%) of the CA3 region. The proportion of PV-IR/SS-LIR neurons in the SS-LIR neurons was low in the SO of the CA1 region (about 10%), but high in the SO (35-65%) and SR (35-45%) of the CA3 region. Morphologically, medium-sized horizontal fusiform and multipolar PV-IR/SS-LIR neurons were frequently observed, and they showed weak immunoreactivity for PV. Large-sized vertical bitufted and triangular PV-ER neurons lacked SS-like immunoreactivity, and most of them showed moderate to intense immunoreactivity for PV. Tn addition, we provide direct Evidence that some PV-IR/SS-LIR neurons projected to the medial septum by using retrograde labeling with Fluoro-Gold injection. These observations indicate that PV-IR/SS-LIR neurons constitute a particular subpopulation of hippocampal nonprincipal neurons. (C) 2000 Wiley-Liss, Inc..|
|8.||S Jinno, Y Aika, T Fukuda, T Kosaka, Quantitative analysis of neuronal nitric oxide synthase-immunoreactive neurons in the mouse hippocampus with optical disector, The Journal of Comparative Neurology, 410, 3, 398-412, 1999.08, A detailed quantitative analysis of immunocytochemically identified nonprincipal neurons containing neuronal nitric oxide synthase (nNOS) was performed on the mouse hippocampus, with particular reference to the dorsoventral gradient. The present study applied two variations of a stereologic technique, the optical disector-one that; used confocal laser-scanning microscope optical sections to examine colocalization of nNOS and glutamic acid decarboxylase 67 (GAD67), and the other that used conventional thick sections to examine numerical densities (NDs) and cell sizes of nNOS-immunoreactive (IR) neurons. Colocalization analysis indicated that practically all nNOS-IR neurons (97.6%) were GAD67-IR, whereas a part of the GAD67-IR neurons (about 30%) were nNOS-IR in the whole hippocampus at both dorsal and ventral levels. The percentages of CAD67-IR neurons containing nNOS were higher in the dentate gyrus (DG, about; 50%), and lower in the Ammon's horn (about 20%). Laminar analysis revealed that the majority of GAD67-IR neurons contained nNOS in the stratum lacunosum-moleculare of the CA3 region (about 60%) and in the molecular layer of the DG (about 80%). The NDs of nNOS-IR neurons in the whole hippocampus showed a dorsoventral gradient, which increased from dorsal(1.6 x 10(3)/mm(3)) to ventral (2.2 x 10(3)/mm(3)) levels. The NDs were relatively higher in the principal cell layers, where about 40% of nNOS-IR neurons were situated both in the Ammon's horn and DG. The mean cell sizes of nNOS-IR neurons showed no remarkable laminar differences or dorsoventral gradient in the Ammon's horn, but; they were extensively larger in the hilus of the DG than in other layers. These results indicate that nNOS-IR neurons in the mouse hippocampus represent a subpopulation of gamma-aminobutyric acid (GABA)ergic neurons and suggest that the laminar distributions of nNOS-IR neurons related to possible functional heterogeneity of GABAergic neurons in each hippocampal layer. (C) 1999 Wiley-Liss, Inc..|