FK506-protective effects against trimethyltin neurotoxicity in rats: Hippocampal expression analyses reveal the involvement of periarterial osteopontin

Murakami, Masahiko; Imai, Hideki; Liu, Yongxun; Xü, Xinsheng; Sadamatsu, Miyuki; Nakagami, Ryoichi; Shirakawa, Takafumi; Nakano, Kenji; Kita, Yasuhiro; Yoshida, Kazuyuki; Tsunashima, Koichi; Kato, Nobuo

doi:10.1016/j.neuroscience.2008.01.078

Cited by 21 publications

(23 citation statements)

References 34 publications

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“…A number studies with neural cell lines and primary cultures indicate that TMT exposure produces changes indicative of programmed cell death such as nuclear condensation, DNA fragmentation, membrane blebbing, and caspase activation (Jenkins and Barone, 2004, Kuramoto et al, 2011, Mundy and Freudenrich, 2006). Similar neuronal pathologies were seen in vivo when TMT was given to rat and mice (Fiedorowicz et al, 2001, Morita et al, 2008). Although the mechanisms underlying the neurotoxicity of TMT are still obscure, the damage induced by TMT in neurons is thought to involve several pathways such as oxidative stress, intracellular calcium overload, and mitochondrial damage (Aldridge et al, 1977, Ali et al, 1992, Misiti et al, 2008, Piacentini et al, 2008).…”

Section: Introductionsupporting

confidence: 58%

Neurotoxicity of Trimethyltin in Rat Cochlear Organotypic Cultures

Ding

Sun

et al. 2015

Neurotox Res

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Trimethyltin (TMT), which has a variety of applications in industry and agricultural is a neurotoxin that is known to affect the auditory system as well as central nervous system (CNS) of humans and experimental animals. However, the mechanisms underlying TMT-induced auditory dysfunction are poorly understood. To gain insights into the neurotoxic effect of TMT on the peripheral auditory system, we treated cochlear organotypic cultures with concentrations of TMT ranging from 5 to 100 μM for 24 h. Interestingly, TMT preferentially damaged auditory nerve fibers and spiral ganglion neurons in a dose-dependent manner, but had no noticeable effects on the sensory hair cells at the doses employed. TMT-induced damage to auditory neurons was associated with significant soma shrinkage, nuclear condensation and activation of caspase-3, biomarkers indicative of apoptotic cell death. Our findings show that TMT is exclusively neurotoxicity in rat cochlear organotypic culture and that TMT-induced auditory neuron death occurs through a caspase-mediated apoptotic pathway.

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Section: Introductionsupporting

confidence: 58%

Neurotoxicity of Trimethyltin in Rat Cochlear Organotypic Cultures

Ding

Sun

et al. 2015

Neurotox Res

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“…OPN increased robustly 24 h postinjury, tracking acute inflammation. Its rapid elevation occurs following toxic insult (Morita et al, 2008), stroke (Wang et al, 1998), ischemia (Lee et al, 1999; van Velthoven et al, 2011) and spinal cord injury (SCI) (Hashimoto et al, 2003; Moon et al, 2004). OPN normalization by 7d points to an inflammatory role supporting acute degeneration.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin expression in acute immune response mediates hippocampal synaptogenesis and adaptive outcome following cortical brain injury

Chan

Reeves

Phillips

2014

Experimental Neurology

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Traumatic brain injury (TBI) produces axotomy, deafferentation and reactive synaptogenesis. Inflammation influences synaptic repair, and the novel brain cytokine osteopontin (OPN) has potential to support axon regeneration through exposure of its integrin receptor binding sites. This study explored whether OPN secretion and proteolysis by matrix metalloproteinases (MMPs) mediate the initial degenerative phase of synaptogenesis, targeting reactive neuroglia to affect successful repair. Adult rats received unilateral entorhinal cortex lesion (UEC) modeling adaptive synaptic plasticity. Over the first week postinjury, hippocampal OPN protein and mRNA were assayed and histology performed. At 1–2d, OPN protein increased up to 51 fold, and was localized within activated, mobilized glia. OPN transcript also increased over 50 fold, predominantly within reactive microglia. OPN fragments known to be derived from MMP proteolysis were elevated at 1d, consistent with prior reports of UEC glial activation and enzyme production. Postinjury minocycline immunosuppression attenuated MMP-9 gelatinase activity, which was correlated with reduction of neutrophil gelatinase-associated lipocalin (LCN2) expression, and reduced OPN fragment generation. The antibiotic also attenuated removal of synapsin-1 positive axons from the deafferented zone. OPN KO mice subjected to UEC had similar reduction of hippocampal MMP-9 activity, as well as lower synapsin-1 breakdown over the deafferented zone. MAP1B and N-cadherin, surrogates of cytoarchitecture and synaptic adhesion, were not affected. OPN KO mice with UEC exhibited time dependent cognitive deficits during the synaptogenic phase of recovery. This study demonstrates that OPN can mediate immune response during TBI synaptic repair, positively influencing synapse reorganization and functional recovery.

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“…Immunohistochemical analysis reported that FK506 had a negative effect in osteopontin (OPN) induction by TMT in the periarterial area. From this study Kato et al suggested that inflammatory gene expression is involved in TMTinduced damage to the hippocampal CA1 region, resulting in apoptosis, and that this process is initiated by periarterial OPN activation, which can be alleviated by FK506 [76]. Additionally, the treatment with kainic acid (KA) causes neuronal death in organotypic hippocampal slice cultures (OHSCs), this neuronal death was significantly relevant in the CA3 region.…”

Section: Role Of Immunophilins In Neuroprotectionmentioning

confidence: 84%

Immunophilin Dysfunction and Neuropathology

Park

Rosado²,

Redondo³

et al. 2011

CMC

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In case of nervous damages, like nervous system trauma or various neurodegenerative diseases such as dementia or Parkinson, several treatments are available to restore neurological function. In spite of these treatments, results are often insufficient or not satisfactory in many neurologic diseases, especially for central nervous system (CNS) lesions. To minimize neurological dysfunction, it is critical to reduce neuronal death, avoiding loss of the synaptic connections, and securing viable neurons to extend axons. Unfortunately, there are no effective strategies to fulfill these basic needs except for some cases of peripheral neural damage up to now. Rescue of damaged neurons, stimulation of neurogenesis and transplantation of nervous tissue are strategies proposed to prevent neurodegenerative disorders. A number of studies have recently reported successful axon regeneration and neurological recovery by using immunosuppressants, such as FK506. Immunosuppressants act as excellent agents for enhancing the rate and extent of axon regeneration and neurological recovery. FK506 and other neuroimmunophilin ligands (NILs) might reverse neuronal degeneration. In several animal models mimicking Parkinson's disease, dementia and surgical damage, NILs induces resprouting, by acting as neurotrophic agents and preventing nerve damage, although more studies are necessary to identify new NILs with neuroprotective action, but lacking the side immunological effects observed in the ligands analyzed to date. This review explores the new clinical role of immunosuppressants in the treatment of nerve surgery of autologous, allografts or xenografts. Results of studies regarding immunosuppressant treatment of nervous system trauma and neurodegenerative diseases, like neurogenic erectile dysfunction, will be here considered.

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FK506-protective effects against trimethyltin neurotoxicity in rats: Hippocampal expression analyses reveal the involvement of periarterial osteopontin

Cited by 21 publications

References 34 publications

Neurotoxicity of Trimethyltin in Rat Cochlear Organotypic Cultures

Neurotoxicity of Trimethyltin in Rat Cochlear Organotypic Cultures

Osteopontin expression in acute immune response mediates hippocampal synaptogenesis and adaptive outcome following cortical brain injury

Immunophilin Dysfunction and Neuropathology

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