A novel model of sensorineural hearing loss induced by repeated exposure to moderate noise in mice: the preventive effect of resveratrol.

Sensorineural hearing loss (SNHL) induced by noise has increased in recent years due to personal headphone use and noisy urban environments. The study shows a novel model of gradually progressive SNHL induced by repeated exposure to moderate noise (8-kHz octave band noise, 90-dB sound pressure level) for 1 hr exposure per day in BALB/cCr mice. The results showed that the repeated exposure led to gradually progressive SNHL, which was dependent on the number of exposures, and resulted in permanent hearing loss after 5 exposures.

Treatment with cyclophosphamide in post-weaning mice causes prolonged suppression of neural stem cell proliferation in the hippocampal dentate gyrus.

The effects of anticancer drugs used in childhood on brain function in adulthood are unclear. Here, we report the long-term changes in the proliferation of neuronal stem/progenitor cells (NPCs) in the hippocampal dentate gyrus after treatment with cyclophosphamide (CYP), which is often used as a therapeutic medicine in childhood cancer. A systemic injection of CYP into 3-week-old mice decreased 5-bromo-2'-deoxyuridine (BrdU)-incorporated cells in the hippocampal subgranular zone 2 and 55 days after the injection in a dose-dependent manner.

(L.) Wettst. Extract Improves Memory Performance via Promotion of Neurogenesis in the Hippocampal Dentate Gyrus of Adolescent Mice.

L. Wettst. (BM) is a botanical component of Ayurvedic medicines and of dietary supplements used worldwide for cognitive health and function.

Interleukin-19 as an Immunoregulatory Cytokine.

IL-19 is a type of anti-inflammatory cytokine. Since the receptor for IL-19 is common to IL-20 and IL-24, it is important to clarify the role of each of the three cytokines. If three different cytokines bind to the same receptor, these three may have been produced to complement the other two.

Bacopa monnieri (L.) Ameliorates Cognitive Deficits Caused in a Trimethyltin-Induced Neurotoxicity Model Mice.

We previously demonstrated that Bacopa monnier (L.) WETTST. extract (BME) ameliorated cognitive dysfunction in animal models of dementia by enhancing synaptic plasticity-related signaling in the hippocampus and protecting cholinergic neurons in the medial septum.

[Adult Neurogenesis-activating Signals as Therapeutic Targets for Neurodegenerative Disorders].

In most mammalian species, adult neurogenesis appears to occur only in the olfactory bulb and hippocampal dentate gyrus, where neural stem/progenitor cells exist to create new neurons. The discovery of multi-potential neural stem/progenitor cells (NPCs) in the adult brain has precipitated a novel therapeutic strategy for harnessing these endogenous cells to aid in recovery from neurodegenerative disorders. During neurodegeneration, a plethora of endogenous factors, including cytokines, chemokines, neurotransmitters, blood-derived factors, and reactive oxygen species, are released by the activation of resident microglia, astrocytes, and infiltrating peripheral macrophages.

Disruption of Gap Junction-Mediated Intercellular Communication in the Spiral Ligament Causes Hearing and Outer Hair Cell Loss in the Cochlea of Mice.

It is well-known that outer hair cell (OHC) loss occurs in the cochlea of animal models of permanent hearing loss induced by intense noise exposure. Our earlier studies demonstrated the production of hydroxynonenal and peroxynitrite, as well as the disruption of gap junction-mediated intercellular communication (GJIC), in the cochlear spiral ligament prior to noise-induced sudden hearing loss. The goal of the present study was to evaluate the mechanism underlying cochlear OHC loss after sudden hearing loss induced by intense noise exposure.

Preventive effect of curcumin and its highly bioavailable preparation on hearing loss induced by single or repeated exposure to noise: A comparative and mechanistic study.

We sought to determine the preventive effects of curcumin and its highly bioavailable preparation on noise-induced hearing loss in a novel murine model of permanent hearing loss developed by repeated exposure to noise. Upon exposure to noise (8-kHz octave band noise, 90 dB sound pressure level, 1 h), hearing ability was impaired in a temporary and reversible manner. During repeated noise exposure (1-h exposure per day, 5 days), there was a progressive increase in the auditory threshold shift at 12 and 20 kHz.

Calpain inhibitor alleviates permanent hearing loss induced by intense noise by preventing disruption of gap junction-mediated intercellular communication in the cochlear spiral ligament.

Our previous studies demonstrated that intense noise-induced hearing loss might be at least in part due to an oxidative stress-induced decrease in the level of gap junction-composing protein connexins in the spiral ligament (SL) of the cochlear lateral wall structures in mice. Further, an in vivo exposure of mice to intense noise activates calpain in the cochlear SL. Based on these studies, we sought to determine whether a calpain inhibitor would prevent an intense noise exposure from causing hearing loss, disruption of gap junction-mediated intercellular communication (GJIC) in the SL.

Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse.

Thrombin-activated protease-activated receptor (PAR)-1 regulates the proliferation of neural cells following brain injury. To elucidate the involvement of PAR-1 in the neurogenesis that occurs in the adult hippocampus, we examined whether PAR-1 regulated the proliferation of neural stem/progenitor cells (NPCs) derived from the murine hippocampal dentate gyrus. NPC cultures expressed PAR-1 protein and mRNA encoding all subtypes of PAR.

Involvement of calpain in 4-hydroxynonenal-induced disruption of gap junction-mediated intercellular communication among fibrocytes in primary cultures derived from the cochlear spiral ligament.

The endocochlear potential in the inner ear is essential for hearing ability, and maintained by various K(+) transport apparatuses including Na(+), K(+)-ATPase and gap junction-mediated intercellular communication (GJ-IC) in the lateral wall structures of the cochlea. Noise-induced hearing loss is known at least in part due to disruption of GJ-IC resulting from an oxidative stress-induced decrease in connexins (Cxs) level in the lateral wall structures. The purpose of this study was to investigate, using primary cultures of fibrocytes from the cochlear spiral ligament of mice, the mechanism underlying GJ-IC disruption induced by 4-hydroxynonenal (4-HNE), which is formed as a mediator of oxidative stress.

Possible involvement of caspases in proliferation of neocortical neural stem/progenitor cells in the developing mouse brain.

Caspases are well-known enzymes that work as initiators and effectors of apoptosis. To elucidate the role of caspases in neurodevelopment, we sought to determine if caspases are involved in the proliferation of neural stem/progenitor cells (NPCs) in the developing mouse brain. Labeling with 5-bromo-2'-deoxyuridine (BrdU) from days 14 to 18 of pregnant mice revealed that the 18-d old fetus had many BudU-positive cells in its brain.

Beneficial effect of cilostazol-mediated neuronal repair following trimethyltin-induced neuronal loss in the dentate gyrus.

Cilostazol acts as an antiplatelet agent and has other pleiotropic effects based on phosphodiesterase-3-dependent mechanisms. We evaluated whether cilostazol would have a beneficial effect on neuronal repair following hippocampal neuronal damage by using a mouse model of trimethyltin (TMT)-induced neuronal loss/self-repair in the hippocampal dentate gyrus [Ogita et al. (2005) J Neurosci Res 82:609-621]; these mice will hereafter be referred to as impaired animals.

Disruption of ion-trafficking system in the cochlear spiral ligament prior to permanent hearing loss induced by exposure to intense noise: possible involvement of 4-hydroxy-2-nonenal as a mediator of oxidative stress.

Noise-induced hearing loss is at least in part due to disruption of endocochlear potential, which is maintained by various K(+) transport apparatuses including Na(+), K(+)-ATPase and gap junction-mediated intercellular communication in the lateral wall structures. In this study, we examined the changes in the ion-trafficking-related proteins in the spiral ligament fibrocytes (SLFs) following in vivo acoustic overstimulation or in vitro exposure of cultured SLFs to 4-hydroxy-2-nonenal, which is a mediator of oxidative stress. Connexin (Cx)26 and Cx30 were ubiquitously expressed throughout the spiral ligament, whereas Na(+), K(+)-ATPase α1 was predominantly detected in the stria vascularis and spiral prominence (type 2 SLFs).

Lithium promotes neuronal repair and ameliorates depression-like behavior following trimethyltin-induced neuronal loss in the dentate gyrus.

Lithium, a mood stabilizer, is known to ameliorate the stress-induced decrease in hippocampal neurogenesis seen in animal models of stress-related disorders. However, it is unclear whether lithium has beneficial effect on neuronal repair following neuronal damage in neuronal degenerative diseases. Here, we evaluated the effect of in vivo treatment with lithium on the hippocampal neuronal repair in a mouse model of trimethyltin (TMT)-induced neuronal loss/self-repair in the hippocampal dentate gyrus (such mice referred to as "impaired animals") [Ogita et al.

Beneficial in vivo effect of aripiprazole on neuronal regeneration following neuronal loss in the dentate gyrus: evaluation using a mouse model of trimethyltin-induced neuronal loss/self-repair in the dentate gyrus.

Aripiprazole is used clinically as an atypical antipsychotic. We evaluated the effect of in vivo treatment with aripiprazole on the proliferation and differentiation of neural stem/progenitor cells in a mouse model, trimethyltin-induced neuronal loss/self-repair in the hippocampal dentate gyrus (referred as "impaired animals") [Ogita et al., J Neurosci Res.

[Activated microglial cells trigger neurogenesis following neuronal loss in the dentate gyrus of adult mice].

Neurological injuries are widely known to promote neurogenesis in the adult hippocampal dentate gyrus. Our previous studies demonstrated that the granule cells in the hippocampal dentate gyrus are injured and eradicated by treatment with trimethyltin (TMT), with being regenerated in the dentate granule cell layer (GCL) after neuronal loss. Recent collective reports indicate that during brain injury and in neurodegenerative disorders, neurogenesis is controlled by cytokines, chemokines, neurotransmitters, and reactive oxygen/nitrogen species, which are released by dying neurons as well as by activated macrophages, micro-glia, and astrocytes.

In vivo and in vitro treatment with edaravone promotes proliferation of neural progenitor cells generated following neuronal loss in the mouse dentate gyrus.

Edaravone is clinically used in Japan for treatment of patients with acute cerebral infarction. To clarify the effect of edaravone on neurogenesis in the hippocampus following neuronal injury in the hippocampal dentate gyrus, we investigated the effect of in vitro and in vivo treatment with edaravone on the proliferation of neural stem/progenitor cells prepared from the mouse dentate gyrus damaged by trimethyltin (TMT). Histological assessment revealed the presence of large number of nestin(+) cells in the dentate gyrus on days 3 - 5 post-TMT treatment.

Opposing roles of glucocorticoid receptor and mineralocorticoid receptor in trimethyltin-induced cytotoxicity in the mouse hippocampus.

The organotin trimethyltin (TMT) is known to cause neuronal degeneration in the murine brain. Earlier studies indicate that TMT-induced neuronal degeneration is enhanced by adrenalectomy and prevented by exogenous glucocorticoid. The aim of this study was to investigate the regulation of TMT neuroxicity by corticosterone receptors including type I (mineralocorticoid receptor, MR) and type II (glucocorticoid receptor, GR) in adult mice.

Indomethacin ameliorates trimethyltin-induced neuronal damage in vivo by attenuating oxidative stress in the dentate gyrus of mice.

The organotin trimethyltin (TMT) is well known to cause neuronal degeneration in the hippocampal dentate gyrus of mice. The first purpose of the present study was to examine whether the cyclooxygenase (COX) inhibitor indomethacin could ameliorate neuronal degeneration in the dentate gyrus of mice following TMT treatment in vivo. The systemic injection into mice of TMT at 2.

Adult neurogenesis is regulated by endogenous factors produced during neurodegeneration.

Adult neurogenesis is the process of generating new neurons that become integrated into existing circuits after fetal and early postnatal development has ceased. In most mammalian species, adult neurogenesis only appears to occur in the olfactory bulb and the hippocampus, where neural stem/progenitor cells (NPCs) exist to create new neurons. In adult neurogenesis, microenviromental change is thought to provide a specific modulation for maintaining the multi-potent state of these NPCs.

Endogenous nitric oxide generation linked to ryanodine receptors activates cyclic GMP / protein kinase G pathway for cell proliferation of neural stem/progenitor cells derived from embryonic hippocampus.

Nitric oxide (NO) activates the cyclic GMP (cGMP) / protein kinase G (PKG) pathway during physiological processes in numerous types of cells. Here, we evaluated whether this NO/cGMP/PKG pathway is involved in the proliferation of neural stem/progenitor cells (NPCs) derived from the hippocampus of embryonic mice. In culture, the exposure to the NO synthase inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) significantly decreased the number of viable cells and 5-bromo-2'-deoxyuridine (BrdU) incorporation into the cells, as well as the levels of intracellular reactive oxygen species, extracellular NO(2), and intracellular cGMP.

Endogenous Nitric Oxide Generation Linked to Ryanodine Receptors Activates Cyclic GMP / Protein Kinase G Pathway for Cell Proliferation of Neural Stem/Progenitor Cells Derived From Embryonic Hippocampus.

Nitric oxide (NO) activates the cyclic GMP (cGMP) / protein kinase G (PKG) pathway during physiological processes in numerous types of cells. Here, we evaluated whether this NO/cGMP/PKG pathway is involved in the proliferation of neural stem/progenitor cells (NPCs) derived from the hippocampus of embryonic mice. In culture, the exposure to the NO synthase inhibitor N-nitro-l-arginine methyl ester (l-NAME) significantly decreased the number of viable cells and 5-bromo-2'-deoxyuridine (BrdU) incorporation into the cells, as well as the levels of intracellular reactive oxygen species, extracellular NO, and intracellular cGMP.