Nestin expression and glial response in the hippocampus of mice after trimethyltin treatment

Brain Research Bulletin

et al. 2016

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Trimethyltin (TMT) toxicity causes histopathological damage in the hippocampus and induces seizure behaviors in mice. The lesions and symptoms recover spontaneously over time; however, little is known about the precise mechanisms underlying this recovery from TMT toxicity. We investigated changes in the brain-derived neurotrophic factor/extracellular signal-regulated kinases (BDNF/ERK) signaling pathways in the mouse hippocampus following TMT toxicity. Mice (7 weeks old, C57BL/6) administered TMT (2.6 mg/kg intraperitoneally) showed acute and severe neurodegeneration with increased TUNEL-positive cells in the dentate gyrus (DG) of the hippocampus. The mRNA and protein levels of BDNF in the hippocampus were elevated by TMT treatment. Immunohistochemical analysis showed that TMT treatment markedly increased phosphorylated ERK1/2 expression in the mouse hippocampus 1-4 days after TMT treatment, although the intensity of ERK immunoreactivity in mossy fiber decreased at 1-8 days post-treatment. In addition, ERK-immunopositive cells were localized predominantly in doublecortin-positive immature progenitor neurons in the DG. In primary cultured immature hippocampal neurons (4 days in vitro), BDNF treatment alleviated TMT-induced neurotoxicity, via activation of the ERK signaling pathway. Thus, we suggest that BDNF/ERK signaling pathways may be associated with cell differentiation and survival of immature progenitor neurons, and will eventually lead to spontaneous recovery in TMT-induced hippocampal neurodegeneration.

Section: Resultssupporting

confidence: 90%

Section: Discussionmentioning

confidence: 56%

Involvement of BDNF/ERK signaling in spontaneous recovery from trimethyltin-induced hippocampal neurotoxicity in mice

Lee

Yang

Brain Research Bulletin

et al. 2016

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“…In many neurological diseases, astrocytes become activated. Astrocyte activation and reactive gliosis leads to an upregulation of IF proteins . Astrocytes express the IF proteins GFAP, vimentin and nestin, which are linked to phenomena such as cell motility, protein phosphorylation, wound healing, protection of neurons in the ischaemic brain and regenerative responses in various kinds of CNS injury .…”

Section: Introductionmentioning

confidence: 99%

Nestin affects fusion pore dynamics in mouse astrocytes

et al. 2019

Aim Astrocytes play a homeostatic role in the central nervous system and influence numerous aspects of neurophysiology via intracellular trafficking of vesicles. Intermediate filaments (IFs), also known as nanofilaments, regulate a number of cellular processes including organelle trafficking and adult hippocampal neurogenesis. We have recently demonstrated that the IF protein nestin, a marker of neural stem cells and immature and reactive astrocytes, is also expressed in some astrocytes in the unchallenged hippocampus and regulates neurogenesis through Notch signalling from astrocytes to neural stem cells, possibly via altered trafficking of vesicles containing the Notch ligand Jagged‐1. Methods We thus investigated whether nestin affects vesicle dynamics in astrocytes by examining single vesicle interactions with the plasmalemma and vesicle trafficking with high‐resolution cell‐attached membrane capacitance measurements and confocal microscopy. We used cell cultures of astrocytes from nestin‐deficient (Nes−/−) and wild‐type (wt) mice, and fluorescent dextran and Fluo‐2 to examine vesicle mobility and intracellular Ca2+ concentration respectively. Results Nes−/− astrocytes exhibited altered sizes of vesicles undergoing full fission and transient fusion, altered vesicle fusion pore geometry and kinetics, decreased spontaneous vesicle mobility and altered ATP‐evoked mobility. Purinergic stimulation evoked Ca2+ signalling that was slightly attenuated in Nes−/− astrocytes, which exhibited more oscillatory Ca2+ responses than wt astrocytes. Conclusion These results demonstrate at the single vesicle level that nestin regulates vesicle interactions with the plasmalemma and vesicle trafficking, indicating its potential role in astrocyte vesicle‐based communication.

“…TMT is a well‐known neurotoxin that induces neurodegeneration in the hippocampus (Lattanzi et al, 2013; Lee et al, 2014). The TMT neurodegenerative mechanism included impairments in GABAR functions and disturbances in GABAergic inhibitory neurotransmission (Kruger et al, 2005; Nishimura et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Trimethyltin (TMT) is an organo‐tin compound that induces neurotoxicity in the mammalian limbic system, particularly the hippocampus, in experimental animals (Lattanzi et al, 2013; Lee et al, 2014). Exposure to TMT induces neurodegeneration and causes extensive neuronal loss, cognitive impairment, and behavioral dysfunction, including aggressiveness, epileptic seizure, and ataxia (Bertram and Cornett, 1994; Besser et al, 1987; Ishida et al, 1997; Kim et al, 2014a).…”

Section: Introductionmentioning

confidence: 99%

Developmental and degenerative modulation of GABAergic transmission in the mouse hippocampus

Son

Intl J of Devlp Neuroscience

et al. 2015

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γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter involved in synaptic plasticity. GABAergic transmission is also implicated in developmental and degenerative processes in the brain. The goal of the present study was to understand the developmental and degenerative regulation of GABAergic transmission in the mouse hippocampus by examining changes in GABA receptor subunit mRNA levels and GABA-related protein expression during postnatal development of the hippocampus and trimethyltin (TMT)-induced neurodegeneration in the juvenile (postnatal day [PD] 24) and adult hippocampus (PD 56). During postnatal development, the mRNA levels of GABA A receptor (GABAAR) subunits, including α1, α4, β1, β2, and δ; GABA B receptor (GABABR) subunit 2; and the expression of GABA-related proteins, including glutamic acid decarboxylase, vesicular GABA transporter (VGAT), and potassium chloride cotransporter 2 increased gradually in the mouse hippocampus. The results of seizure scoring and histopathological findings in the hippocampus revealed a more pronounced response to the same administered TMT dose in juvenile mice, compared with that in adult mice. The mRNA levels of most GABA receptor subunits in the juvenile hippocampus, excluding GABAAR subunit β3, were dynamically altered after TMT treatment. The mRNA levels of GABAAR subunits γ2 and δ decreased significantly in the adult hippocampus following TMT treatment, whereas the level of GABABR subunit 1 mRNA increased significantly. Among the GABA-related proteins, only VGAT decreased significantly in the juvenile and adult mouse hippocampus after TMT treatment. In conclusion, regulation of GABAergic signaling in the mouse hippocampus may be related to maturation of the central nervous system and the degree of neurodegeneration during postnatal development and TMT-induced neurodegeneration in the experimental animals.