scholarly journals Prenatal Hyperhomocysteinemia Induces Glial Activation and Alters Neuroinflammatory Marker Expression in Infant Rat Hippocampus

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1536
Author(s):  
Anastasiia D. Shcherbitskaia ◽  
Dmitrii S. Vasilev ◽  
Yulia P. Milyutina ◽  
Natalia L. Tumanova ◽  
Anastasiia V. Mikhel ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cognitive Disorders ◽  
Interleukin 10 ◽  
Glial Activation ◽  
Prenatal Hyperhomocysteinemia ◽  
Infant Rat ◽  
Female Wistar Rats ◽  
The Common

Maternal hyperhomocysteinemia is one of the common complications of pregnancy that causes offspring cognitive deficits during postnatal development. In this study, we investigated the effect of prenatal hyperhomocysteinemia (PHHC) on inflammatory, glial activation, and neuronal cell death markers in the hippocampus of infant rats. Female Wistar rats received L-methionine (0.6 g/kg b.w.) by oral administration during pregnancy. On postnatal days 5 and 20, the offspring’s hippocampus was removed to perform histological and biochemical studies. After PHHC, the offspring exhibited increased brain interleukin-1β and interleukin-6 levels and glial activation, as well as reduced anti-inflammatory interleukin-10 level in the hippocampus. Additionally, the activity of acetylcholinesterase was increased in the hippocampus of the pups. Exposure to PHHC also resulted in the reduced number of neurons and disrupted neuronal ultrastructure. At the same time, no changes in the content and activity of caspase-3 were found in the hippocampus of the pups. In conclusion, our findings support the hypothesis that neuroinflammation and glial activation could be involved in altering the hippocampus cellular composition following PHHC, and these alterations could be associated with cognitive disorders later in life.

scholarly journals Microglial Toll-like Receptor 2 Contributes to Kainic Acid-induced Glial Activation and Hippocampal Neuronal Cell Death

2010 ◽  
Vol 285 (50) ◽  
pp. 39447-39457 ◽  
Author(s):  
Jinpyo Hong ◽  
Ik-Hyun Cho ◽  
Kyung Il Kwak ◽  
Eun Cheng Suh ◽  
Jinsoo Seo ◽  
...  
Keyword(s):  
Cell Death ◽  
Kainic Acid ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Glial Activation ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2

scholarly journals Netrin-1 receptor UNC5C cleavage by active δ-secretase enhances neurodegeneration, promoting Alzheimer’s disease pathologies

2021 ◽  
Vol 7 (16) ◽  
pp. eabe4499
Author(s):  
Guiqin Chen ◽  
Seong Su Kang ◽  
Zhihao Wang ◽  
Eun Hee Ahn ◽  
Yiyuan Xia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Death ◽  
Axon Guidance ◽  
Neural Development ◽  
Caspase 3 ◽  
Late Onset ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cognitive Disorders

Netrin-1, a family member of laminin-related secreted proteins, mediates axon guidance and cell migration during neural development. T835M mutation in netrin receptor UNC5C predisposes to the late-onset Alzheimer’s disease (AD) and increases neuronal cell death. However, it remains unclear how this receptor is molecularly regulated in AD. Here, we show that δ-secretase selectively cleaves UNC5C and escalates its proapoptotic activity, facilitating neurodegeneration in AD. Netrin deficiency activates δ-secretase that specifically cuts UNC5C at N467 and N547 residues and enhances subsequent caspase-3 activation, additively augmenting neuronal cell death. Blockade of δ-secretase cleavage of UNC5C diminishes T835M mutant’s proapoptotic activity. Viral expression of δ-secretase–truncated UNC5C fragments into APP/PS1 mice strongly accelerates AD pathologies, impairing learning and memory. Conversely, deletion of UNC5C from netrin-1–depleted mice attenuates AD pathologies and rescues cognitive disorders. Hence, δ-secretase truncates UNC5C and elevates its neurotoxicity, contributing to AD pathogenesis.

Traumatic Brain Injury

2019 ◽  
pp. 503-525
Author(s):  
Irene Cristofori ◽  
Jordan Grafman
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Deficits ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Future Research ◽  
Important Health ◽  
Behavioral Treatments ◽  
Severe Tbi ◽  
External Forces

Traumatic brain injury (TBI) is an alteration in brain structure or function caused by external forces that result in vascular and axonal damage, edema, and neuronal cell death. This chapter examines the spectrum of TBI. TBI is a major cause of death and disability and, therefore, an important health and socioeconomic problem for societies. Individuals surviving a moderate to severe TBI frequently suffer from long-lasting cognitive deficits. Such deficits include different aspects of cognition, such as memory, attention, executive functions, social behavior, and awareness. Protective factors, well-detailed diagnostic criteria, and available pharmacological and behavioral treatments are described. Final considerations on current controversies, knowledge gaps, and future research targets are provided.

scholarly journals Neuroprotective Effects of Chrysin Mediated by Estrogenic Receptors Following Cerebral Ischemia and Reperfusion in Male Rats

2021 ◽  
Vol 12 (1) ◽  
pp. 149-162
Author(s):  
Maryam Khombi Shooshtari ◽  
◽  
Yaghoob Farbood ◽  
Seyed Mohammad Taghi Mansouri ◽  
Mohammad Badavi ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Cognitive Deficits ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Male Rats ◽  
Neuroprotective Effects ◽  
Necrosis Factor Alpha ◽  
Male Wistar Rats

Introduction: Ischemic stroke is one of the leading causes of morbidity and mortality worldwide. Neuroprotective strategies were reported to attenuate cognitive deficits after ischemic incidents. Here we studied the neuroprotective potential of chrysin in a rat model of cerebral Ischemia/Reperfusion (I/R) in the presence or absence of Estrogen Receptors (ERs). Methods: Adult male Wistar rats were pretreated with chrysin (CH) (CH; 30 mg/kg; gavage; for 21 consecutive days) alone or with selective ERs antagonists (ERα antagonist MPP; ERβ antagonist PHTPP; IP) or nonselective ERs antagonist (ICI182780; IP). Then, the bilateral common carotid arteries were occluded for 20 min, which was followed by 72 h reperfusion. Subsequently, cognitive performance was evaluated by Morris Water Maze (MWM) and shuttle box tasks, and afterward, their hippocampi were removed for ELISA assays and H&E staining. Oxidative indicators Malondialdehyde (MDA) and Glutathione Peroxidase (GPx), as well as inflammation mediators interleukin (IL)-1β and tumor necrosis factor-alpha (TNFα), were measured using commercial kits. Results: Results of the current study showed that the anti-oxidative and anti-inflammatory properties of CH are possible mechanisms that could improve cognitive deficits and prevent neuronal cell death following I/R (P<0.001). These effects were reversed by ICI182780 (P>0.05). Furthermore, when chrysin was co-treated with ERβ antagonist, PHTPP showed a weak neuroprotective effect in I/R rats. However, these parameters were not significantly different when chrysin was combined with ERα antagonist MPP. Conclusion: Our data confirm that chrysin could potentially serve as a neuroprotective agent against devastating effects of cerebral I/R injury, which may be mediated via its interaction with ERs, especially ERβ.

scholarly journals Expression of 150-kd Oxygen-Regulated Protein in the Hippocampus Suppresses Delayed Neuronal Cell Death

2002 ◽  
Vol 22 (8) ◽  
pp. 979-987 ◽  
Author(s):  
Mayuki Miyazaki ◽  
Kentaro Ozawa ◽  
Osamu Hori ◽  
Yasuko Kitao ◽  
Kohji Matsushita ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Stress Protein ◽  
Neuronal Cell ◽  
Ischemic Insult ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
The Common ◽  
Delayed Neuronal Cell Death

ORP150—150-kd oxygen-regulated protein—is a novel stress protein localized in the endoplasmic reticulum (ER). To investigate the role of ORP150 in delayed neuronal cell death, the authors examined its expression in the gerbil brain after an ischemic insult. The expression of ORP150 antigen, as well as its transcripts, was observed in the CA1 region after the occlusion of the common carotid artery, and the preconditioning enhanced this expression. In cultured neurons, exposure either to hypoxia or to glutamate induced the expression of ORP150, and this effect was also observed by treating the culture with breferdin A or thapsigargin, indicating that both glutamate and hypoxia can cause stress in the ER (ER stress). Neurons became more vulnerable to these stresses following treatment with cycloheximide or after infection with an adenovirus carrying the ORP150-antisense structure. In contrast, the overexpression of ORP150 by an adenovirus suppressed neuronal cell death, and this was accompanied by the suppression of Ca2+ elevation and proteolytic activity induced by glutamate. Further, overexpression of ORP150 in CA1 neurons by an adenovirus carrying the ORP150-sense structure suppressed delayed neuronal cell death after ischemia. These data suggest a possible function of ORP150 as an intracellular apparatus that participates in a protective response in ischemic tolerance.

scholarly journals HDAC8 Inhibitor WK2-16 Therapeutically Targets Lipopolysaccharide-Induced Mouse Model of Neuroinflammation and Microglial Activation

2019 ◽  
Vol 20 (2) ◽  
pp. 410 ◽  
Author(s):  
Fan-Li Lin ◽  
Jing-Lun Yen ◽  
Yu-Cheng Kuo ◽  
Jaw-Jou Kang ◽  
Yu-Wen Cheng ◽  
...  
Keyword(s):  
Microglial Activation ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Mapk Signaling ◽  
Glial Activation ◽  
Immunofluorescent Staining ◽  
Neuroprotective Effects ◽  
Cox 2

Glial activation and neuroinflammatory processes play important roles in the pathogenesis of brain abscess and neurodegenerative diseases. Activated glial cells can secrete various proinflammatory cytokines and neurotoxic mediators, which contribute to the exacerbation of neuronal cell death. The inhibition of glial activation has been shown to alleviate neurodegenerative conditions. The present study was to investigate the specific HDAC8 inhibitor WK2-16, especially its effects on the neuroinflammatory responses through glial inactivation. WK2-16 significantly reduced the gelatinolytic activity of MMP-9, and expression of COX-2/iNOS proteins in striatal lipopolysaccharide (LPS)-induced neuroinflammation in C57BL/6 mice. The treatment of WK2-16 markedly improved neurobehavioral deficits. Immunofluorescent staining revealed that WK2-16 reduced LPS-stimulated astrogliosis and microglial activation in situ. Consistently, cellular studies revealed that WK2-16 significantly suppressed LPS-induced mouse microglia BV-2 cell proliferation. WK2-16 was proven to concentration-dependently induce the levels of acetylated SMC3 in microglial BV-2 cells. It also reduced the expression of COX-2/iNOS proteins and TNF-α production in LPS-activated microglial BV-2 cells. The signaling studies demonstrated that WK2-16 markedly inhibited LPS-activated STAT-1/-3 and Akt activation, but not NF-κB or MAPK signaling. In summary, the HDAC8 inhibitor WK2-16 exhibited neuroprotective effects through its anti-neuroinflammation and glial inactivation properties, especially in microglia in vitro and in vivo.

scholarly journals Deficiency in interleukin-18 ameliorated glial activation and neuroinflammation after traumatic brain injury in mice

2020 ◽  
Author(s):  
Wenwen Dong ◽  
Linlin Wang ◽  
Ziyuan Chen ◽  
Xiangshen Guo ◽  
Pengfei Wang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Cell Death ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Glial Activation ◽  
Neurological Deficits ◽  
Secondary Injury ◽  
Gm Csf ◽  
Tnf Α

Abstract Background: Neuroinflammation is recognized as one of the main pathological mechanisms of secondary injury caused by traumatic brain injury (TBI). It has been reported that interleukin (IL)-18 is expressed in glial cells and involved in the regulation of neuroinflammation. Further studies have revealed that IL-18 expression is upregulated and may contribute to pathogenesis in the later phases of TBI; however, the mechanism underlying the effect of IL-18 on TBI remains unclear. Our present study assessed the roles of IL-18 in inflammatory and neurodegenerative pathology in mice subjected to TBI.Methods: A controlled cortical impact (CCI) injury model was conducted to mimic TBI, and brains were collected at 3 and 7 days post TBI (dpi). The levels of IL-18 were detected by qRT-PCR and immunofluorescence staining. In addition, neurological severity score (NSS) was used to assess neurological deficits after TBI. Furthermore, neuronal cell death, glial activation, and inflammatory cytokine and chemokine secretion were evaluated in wild-type ( WT ) and Il18-knockout ( Il18 -KO) mice to explore the role of IL-18 in TBI.Results: IL-18 levels were upregulated post TBI, accompanied by reactive glial activation. Il-18 deficiency significantly ameliorated glial activation and improved neuronal cell death and neurological deficits. In addition, Il-18 deficiency reduced the TBI-induced M1-like microglia frequency. Interestingly, the levels of all pro- and anti-inflammatory cytokines, including IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL17A, G-CSF, GM-CSF, IFN-γ, and TNF-α, were downregulated in Il18 -KO mice. The deletion of Il-18 attenuated the levels of most chemokines induced by TBI, including CCL2, CCL3, CCL4, CCL5, CCL7, CCL12, CCL20, CXCL1, CXCL2, CXCL10, CXCL12, CXCL13, and CXCL16.Conclusions: These data demonstrated that IL-18 is involved in TBI induced neuroinflammation, which suggests that IL-18 is important for the development of secondary injury induced by TBI.

scholarly journals Humanin Inhibits Neuronal Cell Death by Interacting with a Cytokine Receptor Complex or Complexes Involving CNTF Receptor α/WSX-1/gp130

2009 ◽  
Vol 20 (12) ◽  
pp. 2864-2873 ◽  
Author(s):  
Yuichi Hashimoto ◽  
Megumi Kurita ◽  
Sadakazu Aiso ◽  
Ikuo Nishimoto ◽  
Masaaki Matsuoka
Keyword(s):  
Neuronal Cells ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cytokine Receptor ◽  
Receptor Subunit ◽  
Loss Of Function ◽  
Binding Assays ◽  
The Common ◽  
Receptor Family

Humanin (HN) inhibits neuronal death induced by various Alzheimer's disease (AD)-related insults via an unknown receptor on cell membranes. Our earlier study indicated that the activation of STAT3 was essential for HN-induced neuroprotection, suggesting that the HN receptor may belong to the cytokine receptor family. In this study, a series of loss-of-function tests indicated that gp130, the common subunit of receptors belonging to the IL-6 receptor family, was essential for HN-induced neuroprotection. Overexpression of ciliary neurotrophic factor receptor α (CNTFR) and/or the IL-27 receptor subunit, WSX-1, but not that of any other tested gp130-related receptor subunit, up-regulated HN binding to neuronal cells, whereas siRNA-mediated knockdown of endogenous CNTFR and/or WSX-1 reduced it. These results suggest that both CNTFR and WSX-1 may be also involved in HN binding to cells. Consistent with these results, loss-of-functions of CNTFR or WSX-1 in neuronal cells nullified their responsiveness to HN-mediated protection. In vitro–reconstituted binding assays showed that HN, but not the other control peptide, induced the hetero-oligomerization of CNTFR, WSX-1, and gp130. Together, these results indicate that HN protects neurons by binding to a complex or complexes involving CNTFR/WSX-1/gp130.

The Red Neuronal Pigment in the Nervous System of the Mussel, Mytilus Edulis: Localization and Its Effect on Lateral Ciliary Activity with Spectral and Analytical Changes

1981 ◽  
Vol 39 ◽  
pp. 494-495
Author(s):  
Anthony A. Paparo ◽  
Judith A. Murphy
Keyword(s):  
Nervous System ◽  
Mytilus Edulis ◽  
Neuronal Cell ◽  
Ciliary Activity ◽  
Neuronal Cell Bodies ◽  
The Central Nervous System ◽  
Intracellular Organelles ◽  
The Common ◽  
The Individual ◽  
Cryostat Sections

The purpose of this study was to localize the red neuronal pigment in Mytilus edulis and examine its role in the control of lateral ciliary activity in the gill. The visceral ganglia (Vg) in the central nervous system show an over al red pigmentation. Most red pigments examined in squash preps and cryostat sec tions were localized in the neuronal cell bodies and proximal axon regions. Unstained cryostat sections showed highly localized patches of this pigment scattered throughout the cells in the form of dense granular masses about 5-7 um in diameter, with the individual granules ranging from 0.6-1.3 um in diame ter. Tissue stained with Gomori's method for Fe showed bright blue granular masses of about the same size and structure as previously seen in unstained cryostat sections.Thick section microanalysis (Fig.l) confirmed both the localization and presence of Fe in the nerve cell. These nerve cells of the Vg share with other pigmented photosensitive cells the common cytostructural feature of localization of absorbing molecules in intracellular organelles where they are tightly ordered in fine substructures.

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