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astrocytes and neurodegenerative disease

Ebtisam A Al-Ofi, Badrah S Al-Ghamdi
Neuroinflammation has a definitive role in neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. In addition to its pathogenic ligands, toll-like receptors (TLRs) can be activated by damaged endogenous molecules that induce inflammatory signalling pathways such as high-mobility group box 1 protein (HMGB1). Using an ex-vivo rat optic nerve (RON) model, we sought to determine the effects of lipopolysaccharides (LPS; TLR4 agonist), zymosan (TLR2 agonist) or HMGB1-with or without TLR2/4 antagonists, on the expression of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NF-ҡβ) for signalling pathway and astrocyte reactivity, using double immunohistochemistry; as well as on the modulation of the neurotoxicity...
August 14, 2018: Folia Morphologica (Warsz)
John C O'Donnell, Kritika S Katiyar, Kate V Panzer, D Kacy Cullen
New neurons are integrated into the circuitry of the olfactory bulb throughout the lifespan in the mammalian brain-including in humans. These new neurons are born in the subventricular zone and subsequently mature as they are guided over long distances via the rostral migratory stream through mechanisms we are only just beginning to understand. Regeneration after brain injury is very limited, and although some neuroblasts from the rostral migratory stream will leave the path and migrate toward cortical lesion sites, this neuronal replacement is generally not sustained and therefore does not provide enough new neurons to alleviate functional deficits...
August 2018: Neural Regeneration Research
Yiwei Wang, Yinan Chen, Qin Zhou, Jiawen Xu, Qingqing Qian, Pengfei Ni, Yanning Qian
Recent research has revealed that uncontrolled chronic neuroinflammation is closely associated with diverse neurodegenerative diseases, by impairing blood-brain barrier (BBB) function and astrocytic reaction. Endoplasmic reticulum (ER) stress is conventionally linked to the loss of neuronal structure and function and should be widely attenuated. This notion has been questioned by recent experimental studies, which have shown that non-harmful levels of ER stress had numerous beneficial roles against neurodegeneration, including neuroprotection and inhibition of cytokine production...
2018: Frontiers in Cellular Neuroscience
Michaeline L Hebron, Monica Javidnia, Charbel E-H Moussa
Tau hyperphosphorylation is a critical factor in neurodegenerative diseases, including dementia and Parkinsonism. Existing animal models of tauopathies express tau in neurons within the forebrain and do not often show tau accumulation in the brainstem and astrocytes. This study aims to understand the effects of differential regional expression of tau on neurotransmitter balance in the brain. To obtain an animal model that expresses tau in the brainstem, we bred hemizygous mice that express P301L tau (TauP301L) and detected hyper-phosphorylated tau (p-tau) predominantly in the hippocampus, cortex, brainstem and thalamus...
August 15, 2018: Journal of the Neurological Sciences
Giampiero Leanza, Rosario Gulino, Robert Zorec
In the past, manipulation of the cholinergic system was seen as the most likely therapeutic for neurodegeneration-based cognitive decline in Alzheimer's disease (AD) (Whitehouse et al., 1982). However, targeting the noradrenergic system also seems a promising strategy, since more recent studies revealed that in post-mortem tissue from patients with AD and other neurodegenerative disorders there is a robust correlation between cognitive decline and loss of neurons from the Locus coeruleus (LC), a system with diffuse noradrenaline (NA) innervation in the central nervous system (CNS)...
2018: Frontiers in Molecular Neuroscience
Minji Bang, Onjeon Ryu, Do Gyeong Kim, Darine Froy Mabunga, Kyu Suk Cho, Yujeong Kim, Seol-Heui Han, Kyoung Ja Kwon, Chan Young Shin
Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation...
August 10, 2018: Biomolecules & Therapeutics
Ryota Kobayashi, Hiroshi Hayashi, Shinobu Kawakatsu, Aiko Ishiki, Nobuyuki Okamura, Hiroyuki Arai, Koichi Otani
BACKGROUND: Semantic variant primary progressive aphasia (svPPA) is a subtype of primary progressive aphasia characterized by two-way anomia and disturbance in word comprehension, with focal atrophy in the left temporal lobe. [18 F]THK-5351 was originally developed to trace tau protein. However, it has recently been suggested that [18 F]THK-5351 binds to monoamine oxidase B in astrocytes, which reflects gliosis. Herein, the authors present two cases involving patients with early-stage svPPA who underwent [18 F]THK-5351 positron emission tomography (PET) imaging, and examined whether [18 F]THK-5351 PET imaging is more sensitive to neurodegenerative lesions than conventional imaging modalities such as magnetic resonance imaging (MRI) and cerebral blood flow (CBF)-single photon emission computed tomography (SPECT)...
August 8, 2018: BMC Neurology
Ge Li, Xiaofei He, Hang Li, Yu'e Wu, Yalun Guan, Shuhua Liu, Huanhuan Jia, Yunfeng Li, Lijing Wang, Ren Huang, Zhong Pei, Yue Lan, Yu Zhang
Aging is associated with impairment of the paravascular pathway caused by the activation of astrocytes and depolarization of protein aquaporin‑4 (AQP4) water channels, resulting in the accumulation of protein waste, including amyloid β (Aβ), in the brain parenchyma. The secreted glycoprotein slit guidance ligand 2 (Slit2) is important in regulating the function of the central nervous system and inflammatory response process. In the present study, 15‑month‑old Slit2 overexpression transgenic mice (Slit2‑Tg mice) and two‑photon fluorescence microscopy were used to evaluate the dynamic clearance of the paravascular pathway and the integrity of the blood‑brain barrier (BBB)...
October 2018: International Journal of Molecular Medicine
Robert H Baloh, Jonathan D Glass, Clive N Svendsen
PURPOSE OF REVIEW: This review analyses the recent efforts to develop therapeutics using transplantation of stem cells for amyotrophic lateral sclerosis (ALS). RECENT FINDINGS: Stem cells are considered as a potential therapeutic for a variety of neurodegenerative diseases, in an effort to either replace cells that are lost, or to enhance the survival of the remaining cells. In ALS, meaningful attempts to verify the safety and feasibility of many cell transplantation approaches have only recently been completed or are underway...
August 4, 2018: Current Opinion in Neurology
Isidro Ferrer
Oligodendrocytes are in contact with neurons, wrap axons with a myelin sheath that protects their structural integrity, and facilitate nerve conduction. Oligodendrocytes also form a syncytium with astrocytes which interacts with neurons, promoting reciprocal survival mediated by activity and by molecules involved in energy metabolism and trophism. Therefore, oligodendrocytes are key elements in the normal functioning of the central nervous system. Oligodendrocytes are affected following different insults to the central nervous system including ischemia, traumatism, and inflammation...
August 2, 2018: Progress in Neurobiology
Mariana S Vieira, Anderson K Santos, Rebecca Vasconcellos, Vânia A M Goulart, Ricardo C Parreira, Alexandre H Kihara, Henning Ulrich, Rodrigo R Resende
The abilities of stem cells to self-renew and form different mature cells expand the possibilities of applications in cell-based therapies such as tissue recomposition in regenerative medicine, drug screening, and treatment of neurodegenerative diseases. In addition to stem cells found in the embryo, various adult organs and tissues have niches of stem cells in an undifferentiated state. In the central nervous system of adult mammals, neurogenesis occurs in two regions: the subventricular zone and the dentate gyrus in the hippocampus...
August 2, 2018: Biotechnology Advances
Douglas G Walker, Tiffany M Tang, Lih-Fen Lue
The focus of this study is the expression of Toll-like receptor-3 (TLR-3), a receptor for double-stranded RNA, in human brains affected by Alzheimer's disease (AD) pathology. Toll-like receptors are a family of pattern recognition molecules primarily involved in host defenses to microbial pathogens, but roles in neurodegenerative disease have also been shown, as amyloid beta (Aβ) can be a ligand for TLR-2 and -4 and α-synuclein for TLR-1 and TLR-2, while TLR-9 activation promotes Aβ removal. However, involvement of TLR-3 in AD has not been rigorously studied...
August 1, 2018: Experimental Neurology
Xiaotian Xu, Aiwu Zhang, Yingting Zhu, Wen He, Wei Di, Yannan Fang, Xiaolei Shi
Recent evidence have suggested that neuroinflammation and ischemia induce the activation of two different types of reactive astrocytes, termed A1 and A2. Additionally, A1 astrocytes contribute to the death of neurons and oligodendrocytes in neurodegenerative diseases, such as Alzheimer's disease (AD). In the current study, we constructed an Aβ42-activated microglia-conditioned medium to induce A1 astrocytic activation via secretion of interleukin 1α, tumor necrosis factor, and complement component 1q in vitro, and indicated the regulatory role of milk fat globule epidermal growth factor 8 (MFG-E8) on A1/A2 astrocytic alteration through the downregulation of nuclear factor-κB and the upregulation of PI3K-Akt...
August 4, 2018: Journal of Cellular Physiology
Smith Sylvia B, Wang Jing, Cui Xuezhi, Mysona Barbara, Zhao Jing, Bollinger Kathryn E
Retinal degenerative diseases are major causes of untreatable blindness worldwide and efficacious treatments for these diseases are sorely needed. A novel target for treatment of retinal disease is the transmembrane protein Sigma 1 Receptor (Sig1R). This enigmatic protein is an evolutionary isolate with no known homology to any other protein. Sig1R was originally thought to be an opioid receptor. That notion has been dispelled and more recent pharmacological and molecular studies suggest that it is a pluripotent modulator with a number of biological functions, many of which are relevant to retinal disease...
July 31, 2018: Progress in Retinal and Eye Research
Jennifer L Mantle, Kelvin H Lee
Inflammation can be a risk factor for neurodegenerative diseases such as Alzheimer's disease (AD) and may also contribute to the progression of AD. Here, we sought to understand how inflammation affects the properties of the brain microvascular endothelial cells (BMECs) that compose the blood-brain barrier (BBB), which is impaired in AD. A fully human in vitro BBB model with brain microvascular endothelial cells derived from induced pluripotent stem cells and differentiating neural stem cell (NSC)-derived astrocytic cells was used to investigate the effects of neuroinflammation on barrier function...
July 31, 2018: Neurobiology of Disease
Jun Go, Tae-Shin Park, Geun-Hee Han, Hye-Yeon Park, Young-Kyoung Ryu, Yong-Hoon Kim, Jung Hwan Hwang, Dong-Hee Choi, Jung-Ran Noh, Dae Youn Hwang, Sanghee Kim, Won Keun Oh, Chul-Ho Lee, Kyoung-Shim Kim
Piperlongumine (PL), a biologically active compound from the Piper species, has been shown to exert various pharmacological effects in a number of conditions, including tumours, diabetes, pain, psychiatric disorders and neurodegenerative disease. In this study, we evaluated the therapeutic effects of PL on hippocampal function and cognition decline in aged mice. PL (50 mg/kg/day) was intragastrically administrated to 23‑month‑old female C57BL/6J mice for 8 weeks. Novel object recognition and nest building behaviour tests were used to assess cognitive and social functions...
July 18, 2018: International Journal of Molecular Medicine
Luke W Bonham, Ethan G Geier, Natasha Z R Steele, Dominic Holland, Bruce L Miller, Anders M Dale, Rahul S Desikan, Jennifer S Yokoyama
There is increasing evidence that metabolic dysfunction plays an important role in Alzheimer's disease (AD). Brain insulin resistance and subsequent impairment of insulin and insulin-like growth factor (IGF) signaling are associated with the neurodegenerative and clinical features of AD. Nevertheless, how the brain insulin/IGF signaling system is altered in AD and the effects of these changes on AD pathobiology are not well understood. IGF binding protein 2 (IGFBP-2) is an abundant cerebral IGF signaling protein and there is early evidence suggesting it associates with AD biomarkers...
2018: Frontiers in Neuroscience
Cezary Grochowski, Elżbieta Radzikowska, Ryszard Maciejewski
Adult mammalian neural stem cells are unique because of their properties, such as differentiation capacity, self-renewal, quiescence, and also because they exist in specific niches, which are the subventricular zone (SVZ) and subgranular zone (SGZ) - the dentate gyrus of the hippocampus. SVZ is situated along the ependymal cell layer, dividing the ventricular area and subventricular zone. There are several sources of neural stem cells such as human embryonic stem cells, human fetal brain-derived neural stem/progenitor cells, human induced pluripotent stem cells, direct reprogrammed astrocytes...
July 18, 2018: Clinical Neurology and Neurosurgery
Roxana Mayra Gorojod, Agustina Alaimo, Soledad Porte Alcon, Jimena Hebe Martinez, María Eugenia Cortina, Elba Susana Vazquez, Mónica Lidia Kotler
Heme Oxygenase-1 (HO-1), a stress- responsive enzyme which catalyzes heme degradation into iron, carbon monoxide, and biliverdin, exerts a neuroprotective role involving many different signaling pathways. In Parkinson disease patients, elevated HO-1 expression levels in astrocytes are involved in antioxidant defense. In the present work, employing an in vitro model of Mn2+ -induced Parkinsonism in astroglial C6 cells, we investigated the role of HO-1 in both apoptosis and mitochondrial quality control (MQC)...
October 1, 2018: Toxicology Letters
N N Shusharina, M V Patrushev, E V Silina, V A Stupin, P F Litvitsky, A S Orlova
AIM: To investigate the expression of transporters of different neurotransmitters (glutamate, aspartate, lactate, choline) in the culture of astrocytes isolated from different regions of the brain (cortex, hippocampus and brainstem) in 3- and 11-day rats. MATERIAL AND METHODS: An experimental study was performed on 24 3- (n=12) and 11-days (n=12) old rats (Rattus norvegicus). The results of high-performance sequencing were analyzed. RESULTS: The expression of glutamate and aspartate transporters in the brainstem of 3-day rats was higher than in other regions, however, an opposite effect was observed in 11-day rats...
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
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