Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication

Dragic, Milorad; Zarić, Marina; Mitrović, Nataša; Nedeljković, Nadežda; Grković, Ivana

doi:10.1016/j.neuroscience.2019.10.022

Cited by 19 publications

(47 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our observation that ISO1 selectively inhibited the astrocyte response after FPI suggests that the astrocytic response may be related to innate immune mechanisms that are initiated after an FPI. This result is consistent with recent work linking two distinct morphotypes of astrocytes to neurodegeneration and the dual roles of astrocytosis in neural damage [ 48 , 49 ]. Furthermore, these data indicate that full length CD74, acting in its capacity as a receptor for MIF, contributes to astrocyte activation, but is not required for neurodegeneration.…”

Section: Discussionsupporting

confidence: 93%

Antagonism of Macrophage Migration Inhibitory Factory (MIF) after Traumatic Brain Injury Ameliorates Astrocytosis and Peripheral Lymphocyte Activation and Expansion

Newell‐Rogers

Rogers

Tobin

et al. 2020

IJMS

View full text Add to dashboard Cite

Traumatic brain injury (TBI) precedes the onset of epilepsy in up to 15–20% of symptomatic epilepsies and up to 5% of all epilepsy. Treatment of acquired epilepsies, including post-traumatic epilepsy (PTE), presents clinical challenges, including frequent resistance to anti-epileptic therapies. Considering that over 1.6 million Americans present with a TBI each year, PTE is an urgent clinical problem. Neuroinflammation is thought to play a major causative role in many of the post-traumatic syndromes, including PTE. Increasing evidence suggests that neuroinflammation facilitates and potentially contributes to seizure induction and propagation. The inflammatory cytokine, macrophage migration inhibitory factor (MIF), is elevated after TBI and higher levels of MIF correlate with worse post-traumatic outcomes. MIF was recently demonstrated to directly alter the firing dynamics of CA1 pyramidal neurons in the hippocampus, a structure critically involved in many types of seizures. We hypothesized that antagonizing MIF after TBI would be anti-inflammatory, anti-neuroinflammatory and neuroprotective. The results show that administering the MIF antagonist ISO1 at 30 min after TBI prevented astrocytosis but was not neuroprotective in the peri-lesion cortex. The results also show that ISO1 inhibited the TBI-induced increase in γδT cells in the gut, and the percent of B cells infiltrating into the brain. The ISO1 treatment also increased this population of B cells in the spleen. These findings are discussed with an eye towards their therapeutic potential for post-traumatic syndromes, including PTE.

show abstract

Section: Discussionsupporting

confidence: 93%

Antagonism of Macrophage Migration Inhibitory Factory (MIF) after Traumatic Brain Injury Ameliorates Astrocytosis and Peripheral Lymphocyte Activation and Expansion

Newell‐Rogers

Rogers

Tobin

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Immunostaining directed to astrocyte marker GFAP showed the presence of pronounced gliosis (Figure 1c). The rst indication of astrogliosis was observed already at 2dpi [28] while the full-blown hypertrophied astrocytes were seen at 7-dpi in CA1 region and atrophy-like morphotype was observed in the hilar/CA3 region. At 21-dpi, hypertrophied/atrophied astrocytes were widespread in CA1 and CA3 sectors, and covered the hilar region in the form of gliotic scar, while CA2 remained devoid of GFAP-ir.…”

Section: Resultsmentioning

confidence: 98%

“…Histochemistry, immunohistochemistry and immuno uorescence microscopy Brains (n = 5 per group) were carefully removed from the skull, xed in 4 % PFA for 24 hours, cryoprotected in graded sucrose (10-30 % in 0.2 M phosphate buffer), and stored at 4°C, as described before [21], [28]. The brains were cryosectioned in serial 25-µm thick coronal sections and the sections at 3.12 -3.84 mm antero-posterior to Bregma were air-dried and stored at -20°C until use.…”

Section: Methodsmentioning

confidence: 99%

“…The toxicant induces a selective and progressive hippocampal neurodegeneration and chronic microgliosis and astrogliosis, which result in behavioral and neurological symptoms and memory dysfunction similar to AD [24]- [27]. In the previous paper, we have described particular reactive astrocyte phenotypes and their dynamic remodeling in TMT-induced neurodegeneration [28]. The TMT-induced reactive astrocyte phenotypes have been previously linked with increased activation of glial P2X 2 R [29].…”

Section: Introductionmentioning

confidence: 96%

“…Given that the involvement of purinergic signaling has not been explored in the TMT model, in the present study, we have analyzed the spatial and temporal patterns of NTPDase1/CD39 and eN/CD73 and purinergic receptors expression in the context of microglia and astrocytes activation. It was previously shown that TMT induced hippocampal neurodegeneration and gliosis, the pattern of which was comparable in adult rats of both sexes [24]- [26], [28], [30], [31]. However, given that the expression of ectonucleotidases in the brain is under the control of gonadal steroids and differs in two sexes [21], [32], [33], the study was performed in female rats, bilaterally ovariectomized three weeks prior to TMT injection [28].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Purinergic Signaling Participates in a Transition Between Functional States of Reactive Microglia and Controls Astrocyte-Driven Neuroinflammation in the Model of Trimethyltin-Induced Neurodegeneration

Dragic¹,

Mitrović²,

Adžić³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

BackgroundThe present study aims to explore the involvement of purinergic signaling in the rodent model of hippocampal degeneration induced by trimethyltin (TMT), which results in behavioral and neurological dysfunction similar to Alzheimer’s disease. Our study has provided novel evidence that TMT induced extracellular depositions of amyloid β, which might be the cause of the well-defined progressive hippocampal neurodegeneration and gliosis. MethodsWe have applied enzyme histochemistry and immunohistochemistry to study spatial and temporal patterns of ectonucleotidase NTPDase1/CD39 and eN/CD73 expression, gene expression analysis and immunochemistry to analyze cellular localization of select purinoreceptors and pro-inflammatory cytokines previously associated with microglia and astrocytes activation. ResultsOur study demonstrated that all Iba1-ir microglial cells, irrespective of the cell shape and localization, upregulated NTPDase1/CD39, while the induction of eN/CD73 has been observed only at amoeboid microglia, localized within the hippocampal layers with pronounced cell death. Marked induction of P2Y12R and P2Y6R at amoeboid microglia might reflect the transition from rod to amoeboid microglia and the adaptation to the migratory and phagocytic properties of the latter. Based on the expression of the microglial polarization markers, the majority of microglia belonged to the M2-like functional state. A significant change in purinergic signaling components accompanied the response of reactive astrocytes, which occupied the areas with pronounced cell death. Reactive astrocytes, which markedly expressed adenosine A2A and P2Y1 receptors, showed massive induction of complement component C3, NF-kB and IL-1β, suggesting that astrocyte-derived inflammation might be responsible for prolonged and spreading neurodegeneration in TMT model.ConclusionThis study put glia-associated purinergic signaling in the center of molecular pathogenesis of AD-like disease. Our findings suggest that the ectonucleotidases and purinergic signaling play significant role in microgliosis, astrocyte-driven neuroinflammation and prolonged neurodegeneration in the TMT model.

show abstract

Trimethyltin as a Model to Explore Mechanisms of Selective Neuronal Death, Glial Reactivity, and Repair

Harry¹

2021

Handbook of Neurotoxicity

View full text Add to dashboard Cite

Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication

Cited by 19 publications

References 74 publications

Antagonism of Macrophage Migration Inhibitory Factory (MIF) after Traumatic Brain Injury Ameliorates Astrocytosis and Peripheral Lymphocyte Activation and Expansion

Antagonism of Macrophage Migration Inhibitory Factory (MIF) after Traumatic Brain Injury Ameliorates Astrocytosis and Peripheral Lymphocyte Activation and Expansion

Purinergic Signaling Participates in a Transition Between Functional States of Reactive Microglia and Controls Astrocyte-Driven Neuroinflammation in the Model of Trimethyltin-Induced Neurodegeneration

Trimethyltin as a Model to Explore Mechanisms of Selective Neuronal Death, Glial Reactivity, and Repair

Contact Info

Product

Resources

About