Mayumi Nishi - Academia.edu (original) (raw)

Papers by Mayumi Nishi

Scientific Reports, 2021

Adverse experience in early life can affect the formation of neuronal circuits during postnatal d... more Adverse experience in early life can affect the formation of neuronal circuits during postnatal development and exert long-lasting influences on neural functions that can lead to the development of a variety of psychiatric disorders including depression, anxiety disorders, and post-traumatic stress disorder. Many studies have demonstrated that daily repeated maternal separation, an animal model of early-life stress, can induce impairments in emotional behaviours and cognitive function during adolescence and adulthood. However, the behavioural phenotypes of maternally separated mice under long-term group-housing conditions are largely unknown. In this study, we applied our newly developed assay system to investigate the effects of maternal separation on behaviours under group-housing conditions during four days of continuous observations. Using our system, we found that repeated maternal separation resulted in inappropriate social distance from cagemates, altered approach preferences...

Journal of Neurosurgery: Spine, 2017

OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a th... more OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a therapeutic strategy in the treatment of spinal cord injury (SCI). Although a scaffold is sometimes used for retaining transplanted cells in damaged tissue, it is also known to induce redundant immunoreactions during the degradation processes. In this study, the authors prepared cell sheets made of BMSCs, which are transplantable without a scaffold, and investigated their effects on axonal regeneration, glial scar formation, and functional recovery in a completely transected SCI model in rats. METHODS BMSC sheets were prepared from the bone marrow of female Fischer 344 rats using ascorbic acid and were cryopreserved until the day of transplantation. A gelatin sponge (GS), as a control, or BMSC sheet was transplanted into a 2-mm-sized defect of the spinal cord at the T-8 level. Axonal regeneration and glial scar formation were assessed 2 and 8 weeks after transplantation by immunohistochemi...

Psychology, 2020

Neonatal maternal separation has been found to affect adult brain function. However, the molecula... more Neonatal maternal separation has been found to affect adult brain function. However, the molecular basis has not been clarified. The purpose of this study was to elucidate the changes in mineral levels related to the antioxidative system in the adult mouse hippocampus after neonatal maternal separation. Male mouse pups in the maternal separation group were separated from their dams for 3 hours daily during the first 2 postnatal weeks. The hippocampal selenium, calcium, zinc, copper, and manganese contents were analyzed with an inductively coupled plasma mass spectrometer at 13 postnatal weeks, and plasma protein carbonyl and 8-OHdG concentrations were examined by enzyme-linked immunosorbent assay. It was found that the hippocampal selenium content was about three times lower in the maternal separation group than that in the control group, representing a significant difference. The hippocampal calcium content was more than 2 times higher in the maternal separation group than that in the control group. The plasma protein carbonyl concentration was about seven-fold higher in the maternal separation group than that in the control group. However, no significant differences were found in the hippocampal calcium, zinc, copper, and manganese contents, or in plasma protein carbonyl and 8-OHdG concentrations between the maternal separation and control groups. Therefore, neonatal maternal separation affects the hippocampal selenium content of adult male mice, but does not affect other mineral contents, such as zinc, copper, manganese, and calcium in the hippocampus.

Anatomical Science International, 2016

The hypothalamus controls metabolism, stress responses, and instinctive behaviors for individual ... more The hypothalamus controls metabolism, stress responses, and instinctive behaviors for individual survival and species preservation. Recent studies suggest that hypothalamic neurons retain plasticity throughout adulthood, which enables these neurons to respond to various kinds of changes in environment, nutrients, and fluctuating hormones. One of the mechanisms underlying the regulation of neural plasticity is the formation of a stable extracellular matrix (ECM) structure called perineuronal nets (PNNs). PNNs are large aggregates of heterogeneous ECM molecules such as chondroitin sulfate proteoglycans (CSPGs), hyaluronan, their link proteins, and tenascin-R. PNNs surround the cell body and proximal dendrites of a subset of neurons and limit adult neural plasticity. This review describes the CSPG-based ECM, including the PNNs, with a special focus on the hypothalamus of mice. We first provide an overview of PNNs in terms of their structure, molecular components, and functions, most of which have been demonstrated by extrahypothalamic studies. Second, we show the presence or absence of PNNs within individual hypothalamic regions and then describe non-PNN-formed ECM containing CSPGs that can be observed in particular hypothalamic regions. Finally, we will introduce a newly identified mouse hypothalamic area that we named the perifornical area of the anterior hypothalamus (PeFAH), which contains a cluster of PNNpositive neurons. PeFAH neurons express enkephalin and have bidirectional connections with the lateral septum. The anterior hypothalamus and lateral septum are thought to regulate defensive behaviors; therefore, the PeFAH neurons and PNNs around them could be involved in the regulation of defensive behaviors.

Acta Histochemica Et Cytochemica, 2001

Acta Histochemica Et Cytochemica, 2005

Neuroscience letters, Jan 22, 2017

Early-life stress has long-lasting effects on the stress response, emotions, and behavior through... more Early-life stress has long-lasting effects on the stress response, emotions, and behavior throughout an individual's life. Clinical reports have demonstrated that child abuse victims exhibit impairments in reward-associated behavior; yet, the mechanism for this effect remains unclear. Maternal separation (MS) or MS coupled with social isolation (SI) (MS+SI) is widely used as a model for early-life stress in rodent studies. We employed mice subjected to MS+SI to clarify the long-term effect of early-life stress on reward-seeking involving palatable foods by a conditioned place-preference (CPP) paradigm. Prior MS+SI experience decreased exploration time in a chocolate-paired compartment in adult female mice, but not in male mice. We then focused on the mesolimbic dopamine pathway associated with reward-seeking behavior and measured both mRNA and protein levels of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and dopamine D1 and D2 receptors in the nucleus accumbens...

Synapse, 1996

Serotonin (5-HT) has been shown to modulate brain maturation during development and adult plastic... more Serotonin (5-HT) has been shown to modulate brain maturation during development and adult plasticity. This effect in the whole animal may be due to activation of 5-HTIA receptors and a corresponding increases in SlOOb and corticosterone. Synaptophysin, an integral protein of the synaptic vesicle membrane that correlates with synaptic density and neurotransmitter release, is reduced by depletion of 5-HT in the cortex and hippocampus of the adult rat. Injections of a 5-HTl~ agonist or dexamethasone can reverse the loss of synaptophysin immunoreactivity (IR). In this study we used morphometric analysis of synaptophysin-IR to study the effects of the 5-HTu agonist, ipsapirone, and the neuronal extension factor, SlOOb on hippocampal neurons grown in a serum and steroid free media. Both compounds increased the synaptophysin-IR at doses previously established to be highly specific. Ipsapirone (M) was more effective on neuronal cell bodies staining and SlOOb (10 ng/ml) was more effective in increasing the number of synaptophysin-IR varicosities on neuronal processes. In addition both types of corticosteroid receptor agonists, at previously established specific doses, Ru28362 M) and aldosterone (M) produced smaller increases compared to control groups in both the cell body staining and the number of varicosities. The effect of these differentiating factors on the expression of synaptophysin-IR suggests multiple regulation sites for producing and maintaining pre-synaptic elements in the brain. o 1996 Wiley-Liss, Inc.

International Journal of Molecular Sciences

Early-life stress during the prenatal and postnatal periods affects the formation of neural netwo... more Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or neglect in humans, can modulate the hypothalamic–pituitary–adrenal (HPA) axis, affecting subsequent neuronal function and emotional behavior. However, the neural basis of the long-lasting effects of early-life stress on brain function has not been clarified. In the present review, we describe the alterations in the HPA-axis activity—focusing on serum corticosterone (CORT)—and in the end products of the HPA axis as well as on the CORT receptor in rodents. We then introduce the brain regions activated during various patterns of MS, including repeated MS and single exposure to MS at various stages before weaning, via an investigation of c-Fos expression, which is a biological mar...

Histochemistry and Cell Biology

Folia Pharmacologica Japonica

Neuroreport, 1994

This study was undertaken to evaluate the short-term effects of glucocorticoid on the morphologic... more This study was undertaken to evaluate the short-term effects of glucocorticoid on the morphological characteristics of cultured rat dentate gyrus (DG) cells using immunocytochemistry for a cytoskeletal protein, micro-tubule-associated protein 2 (MAP2). A selective cell culture system of DG neurons was successfully established. Synthetic glucocorticoid, dexamethasone (DEX) increased the total length of immunoreactive (IR) processes of the DG neurones in a dose-dependent manner. DEX also increased the ratio of multipolar neurones with more than three processes. The area of cell body of immunoreactive processes increased with 5 microM DEX treatment. Our results suggest that cytological features of DG cells are strongly influenced by the action of glucocorticoid.

Scientific Reports, 2016

Although the role of extracellular Ca 2+ draws increasing attention as a messenger in intercellul... more Although the role of extracellular Ca 2+ draws increasing attention as a messenger in intercellular communications, there is currently no tool available for imaging Ca 2+ dynamics in extracellular regions. Here we report the first solid-state fluorescent Ca 2+ sensor that fulfills the essential requirements for realizing extracellular Ca 2+ imaging. Inspired by natural extracellular Ca 2+-sensing receptors, we designed a particular type of chemically-crosslinked polyacrylic acid gel, which can undergo single-chain aggregation in the presence of Ca 2+. By attaching aggregation-induced emission luminogen to the polyacrylic acid as a pendant, the conformational state of the main chain at a given Ca 2+ concentration is successfully translated into fluorescence property. The Ca 2+ sensor has a millimolar-order apparent dissociation constant compatible with extracellular Ca 2+ concentrations, and exhibits sufficient dynamic range and excellent selectivity in the presence of physiological concentrations of biologically relevant ions, thus enabling monitoring of submillimolar fluctuations of Ca 2+ in flowing analytes containing millimolar Ca 2+ concentrations. Ca 2+ plays a crucial role in many important physiological and pathological processes in animals 1-17 and plants 9,18-23. Over the past several decades, many synthetic molecular and genetically encoded fluorescent Ca 2+ indicators have been developed, as represented by 1,2-bis(o-aminophenoxy)-ethane-N,N,N′ ,N′-tetraacetic acid (BAPTA) derivatives 24-27 and calmodulin-based proteins 28-32 , respectively. Ca 2+-imaging techniques that use such fluorescent indicators are indispensable in modern biology and medical science. In living organisms, Ca 2+ concentrations differ greatly depending on the compartment. Typically, the Ca 2+ concentration is ~100 nanomolar (nM) in intracellular cytosol, ~100 micromolar (μM) in the endoplasmic reticulum and mitochondria and ~1 millimolar (mM) in extracellular fluid and blood (Fig. 1a,b) 3. Plant vacuoles are also considered to contain mM-order Ca 2+ concentrations 20. Hence, Ca 2+ imaging in all of these compartments requires dedicated fluorescent indicators with specific dissociation constants (K d) that are appropriate for the respective background Ca 2+ concentrations. However, almost every Ca 2+ indicator known to date has a K d value ranging from nM to μM, and therefore allows for Ca 2+ imaging only in cytosol and organelles (Fig. 1a). Fluorescent Ca 2+ indicators with mM-order K d , compatible with extracellular Ca 2+ concentrations 27,32 , have scarcely been developed 9,10 , despite the fact that extracellular Ca 2+ , which is conventionally regarded as a diagnostic indicator for many diseases 3,7 , is now receiving considerable attention as a first messenger 3-17 in, for example, parathyroid gland 3,4 , neuron 12,13 , myocyte 14 , stem cell 15 and macrophages 16,17. In fact, there are major problems in the development of indicators for extracellular Ca 2+ imaging 9,10. First, such indicators should be designed to strike a balance between mM-order K d (i.e., a rather small affinity for Ca 2+) and high selectivity for Ca 2+ in the presence of excessive amounts of other physiological ions. Although simple Ca 2+ imaging against mM-order background concentration of Ca 2+ may be possible using existing indicators with μM-order K d , Ca 2+ indicators with one-order higher K d have a great advantage in monitoring Ca 2+ transients and oscillations in extracellular regions. Even more challenging in extracellular Ca 2+ imaging, one has to create a mechanism to avoid the outflow of indicators from an observation area through molecular diffusion. Obviously, this issue is intractable with existing molecular-based indicators.

Molecular Endocrinology, Jul 2, 2013

Androgen and estrogen act not only in a sex-specific manner but also interactively and synergisti... more Androgen and estrogen act not only in a sex-specific manner but also interactively and synergistically. In the present study, to examine the possible interaction between androgen receptor (AR) and estrogen receptor-alpha (ERalpha), we investigated the subcellular dynamics of AR and ERalpha fused with green fluorescent protein color variants in single living cells using time-lapse microscopy and the technique of fluorescence recovery after photobleaching. AR and ERalpha showed punctate colocalization in the nucleus with estrogen, but not androgen. N-terminal AR deletion mutant did not form a nuclear punctate pattern with either androgen or estrogen. In the presence of AR, but not ERalpha, N-terminal AR deletion mutant formed a punctate nuclear pattern with androgen. AR had different mobility depending on the ligand and the presence of ERalpha. On the other hand, AR had little effect on the stability of ERalpha. ERalpha mutant that does not bind coactivators did not alter the mobility of AR. Taken together, using an imaging technique, we clarified that possible homo/hetero dimerization between AR and ERalpha could be attributed to androgen-estrogen interaction in living cells.

Acta Histochemica Et Cytochemica, 2002

Proceedings of the Japan Society For Comparative Endocrinology, Nov 3, 2006

Neuroendocrinology, Feb 1, 2007

Adrenal corticosteroids (cortisol in humans/corticosterone in rodents) readily enter the brain an... more Adrenal corticosteroids (cortisol in humans/corticosterone in rodents) readily enter the brain and exert markedly diverse effects, such as the stress response of target neural cells. These effects are regulated via two receptor systems, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), both of which are ligand-inducible transcription factors. It is generally accepted that GR and MR predominantly reside in the cytoplasm in the absence of corticosterone (CORT), and are quickly translocated into the nucleus upon binding CORT. Then these receptors form dimers to bind hormone-responsive elements and regulate the expression of target genes. Given the different actions of MR and GR in the central nervous system, it is important to elucidate how the trafficking of these receptors between the cytoplasm and nucleus and their interaction are regulated by ligands or other molecules to exert transcriptional activity. However, the precise mechanisms of these processes are still not completely clarified. To address these issues, we have tried to observe more dynamic subcellular trafficking processes in living cells by employing a green fluorescent protein. In this review, we describe our recent studies of corticosteroid receptor dynamics in living cells focusing on three points: (1) the effects of a ligand, corticosteroid; (2) the carrier molecules involved in active nuclear transport, importins, and (3) the possibility of heterodimer formation. These studies demonstrate that GR and MR were quickly translocated from the cytoplasm to the nucleus after CORT treatment by associating with importin molecules. GR and MR differed in their response to the concentration of CORT in neural cells and non-neural cells. In the nuclear region, we detected GR-MR heterodimers, which were affected by changes in CORT concentrations in response to various hormonal milieus such as circadian rhythm and stress.