Hypothalamic Sirt1 protects terminal Schwann cells and neuromuscular junctions from age-related morphological changes

Background: Oxidative stress is caused by free radicals or oxidant productions, including lipid peroxidation, protein modification, DNA damage and apoptosis or cell death and results in cellular degeneration and neurodegeneration from damage to macromolecules. Results: Accumulation of the DNA damage (8HOdG) products and the end products of LPO (including aldehyde, diene, triene conjugates and Schiff’s bases) were noted in the research studies. Significantly higher levels of these products in comparison with the controls were observed. Oxidative stress induced changes to ocular cells and tissues. Typical changes include ECM accumulation, cell dysfunction, cell death, advanced senescence, disarrangement or rearrangement of the cytoskeleton and released inflammatory cytokines. It is involved in ocular diseases, including keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, cataract, age-related macular degeneration, primary open-angle glaucoma, retinal light damage, and retinopathy of prematurity. These ocular diseases are the cause of irreversible blindness worldwide. Conclusions: Oxidative stress, inflammation and autophagy are implicated in biochemical and morphological changes in these ocular tissues. The development of therapy is a major target for the management care of these ocular diseases.

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Assessment of age‐related morphological changes in the testes of post‐hatch light ecotype Nigerian indigenous chicken

Anatomia Histologia Embryologia ◽

10.1111/ahe.12649 ◽

2020 ◽

Author(s):

Anietie Francis Udoumoh ◽

Udensi Maduabuchi Igwebuike ◽

Chidozie Nwabuisi Okoye ◽

Ugochukwu Michael Ugwu ◽

Chike Fidelis Oguejiofor

Keyword(s):

Morphological Changes ◽

Indigenous Chicken ◽

Age Related

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Age-Related Changes in the Primary Motor Cortex of Newborn to Adult Domestic Pig Sus scrofa domesticus

Animals ◽

10.3390/ani11072019 ◽

2021 ◽

Vol 11 (7) ◽

pp. 2019

Author(s):

Salvatore Desantis ◽

Serena Minervini ◽

Lorenzo Zallocco ◽

Bruno Cozzi ◽

Andrea Pirone

Keyword(s):

Animal Model ◽

Motor Cortex ◽

Calcium Binding ◽

Sus Scrofa ◽

Primary Motor Cortex ◽

Morphological Changes ◽

Neural Cells ◽

Age Related ◽

Cell Layers ◽

Sus Scrofa Domesticus

The pig has been increasingly used as a suitable animal model in translational neuroscience. However, several features of the fast-growing, immediately motor-competent cerebral cortex of this species have been adequately described. This study analyzes the cytoarchitecture of the primary motor cortex (M1) of newborn, young and adult pigs (Sus scrofa domesticus). Moreover, we investigated the distribution of the neural cells expressing the calcium-binding proteins (CaBPs) (calretinin, CR; parvalbumin, PV) throughout M1. The primary motor cortex of newborn piglets was characterized by a dense neuronal arrangement that made the discrimination of the cell layers difficult, except for layer one. The absence of a clearly recognizable layer four, typical of the agranular cortex, was noted in young and adult pigs. The morphometric and immunohistochemical analyses revealed age-associated changes characterized by (1) thickness increase and neuronal density (number of cells/mm2 of M1) reduction during the first year of life; (2) morphological changes of CR-immunoreactive neurons in the first months of life; (3) higher density of CR- and PV-immunopositive neurons in newborns when compared to young and adult pigs. Since most of the present findings match with those of the human M1, this study strengthens the growing evidence that the brain of the pig can be used as a potentially valuable translational animal model during growth and development.

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Physiological and Pathological Ageing of Astrocytes in the Human Brain

Neurochemical Research ◽

10.1007/s11064-021-03256-7 ◽

2021 ◽

Author(s):

Marloes Verkerke ◽

Elly M. Hol ◽

Jinte Middeldorp

Keyword(s):

Risk Factor ◽

Morphological Changes ◽

Ion Homeostasis ◽

Brain Functioning ◽

Physiological Ageing ◽

Human Astrocytes ◽

Age Related ◽

Technical Issues ◽

Neuronal Transmission ◽

Ageing Brain

AbstractAgeing is the greatest risk factor for dementia, although physiological ageing by itself does not lead to cognitive decline. In addition to ageing, APOE ε4 is genetically the strongest risk factor for Alzheimer’s disease and is highly expressed in astrocytes. There are indications that human astrocytes change with age and upon expression of APOE4. As these glial cells maintain water and ion homeostasis in the brain and regulate neuronal transmission, it is likely that age- and APOE4-related changes in astrocytes have a major impact on brain functioning and play a role in age-related diseases. In this review, we will discuss the molecular and morphological changes of human astrocytes in ageing and the contribution of APOE4. We conclude this review with a discussion on technical issues, innovations, and future perspectives on how to gain more knowledge on astrocytes in the human ageing brain.

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Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard

Archives of Toxicology ◽

10.1007/s00204-020-02946-5 ◽

2021 ◽

Vol 95 (2) ◽

pp. 727-747

Author(s):

Simone Rothmiller ◽

Niklas Jäger ◽

Nicole Meier ◽

Thimo Meyer ◽

Adrian Neu ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Alkylating Agent ◽

Chronic Wounds ◽

Sulfur Mustard ◽

Morphological Changes ◽

Human Mesenchymal Stem Cells ◽

Age Related

AbstractWound healing is a complex process, and disturbance of even a single mechanism can result in chronic ulcers developing after exposure to the alkylating agent sulfur mustard (SM). A possible contributor may be SM-induced chronic senescent mesenchymal stem cells (MSCs), unable to fulfil their regenerative role, by persisting over long time periods and creating a proinflammatory microenvironment. Here we show that senescence induction in human bone marrow derived MSCs was time- and concentration-dependent, and chronic senescence could be verified 3 weeks after exposure to between 10 and 40 µM SM. Morphological changes, reduced clonogenic and migration potential, longer scratch closure times, differences in senescence, motility and DNA damage response associated genes as well as increased levels of proinflammatory cytokines were revealed. Selective removal of these cells by senolytic drugs, in which ABT-263 showed initial potential in vitro, opens the possibility for an innovative treatment strategy for chronic wounds, but also tumors and age-related diseases.

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Effects of innate immune receptor stimulation on extracellular α-synuclein uptake and degradation by brain resident cells

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00562-6 ◽

2021 ◽

Author(s):

Changyoun Kim ◽

Somin Kwon ◽

Michiyo Iba ◽

Brian Spencer ◽

Edward Rockenstein ◽

...

Keyword(s):

Degradation Kinetics ◽

Morphological Changes ◽

Direct Interaction ◽

Innate Immune ◽

Pathological Feature ◽

Tlr2 Expression ◽

Immune Receptors ◽

Age Related ◽

Stimulation Of

AbstractSynucleinopathies are age-related neurological disorders characterized by the progressive deposition of α-synuclein (α-syn) aggregates and include Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Although cell-to-cell α-syn transmission is thought to play a key role in the spread of α-syn pathology, the detailed mechanism is still unknown. Neuroinflammation is another key pathological feature of synucleinopathies. Previous studies have identified several immune receptors that mediate neuroinflammation in synucleinopathies, such as Toll-like receptor 2 (TLR2). However, the species of α-syn aggregates varies from study to study, and how different α-syn aggregate species interact with innate immune receptors has yet to be addressed. Therefore, we investigated whether innate immune receptors can facilitate the uptake of different species of α-syn aggregates. Here, we examined whether stimulation of TLRs could modulate the cellular uptake and degradation of α-syn fibrils despite a lack of direct interaction. We observed that stimulation of TLR2 in vitro accelerated α-syn fibril uptake in neurons and glia while delaying the degradation of α-syn in neurons and astrocytes. Internalized α-syn was rapidly degraded in microglia regardless of whether TLR2 was stimulated. However, cellular α-syn uptake and degradation kinetics were not altered by TLR4 stimulation. In addition, upregulation of TLR2 expression in a synucleinopathy mouse model increased the density of Lewy-body-like inclusions and induced morphological changes in microglia. Together, these results suggest that cell type-specific modulation of TLR2 may be a multifaceted and promising therapeutic strategy for synucleinopathies; inhibition of neuronal and astroglial TLR2 decreases pathogenic α-syn transmission, but activation of microglial TLR2 enhances microglial extracellular α-syn clearance.

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Association of beta-cytoplasmic actin with high concentrations of acetylcholine receptor (AChR) in normal and anti-AChR-treated primary rat muscle cultures.

Journal of Histochemistry & Cytochemistry ◽

10.1177/32.9.6379042 ◽

1984 ◽

Vol 32 (9) ◽

pp. 973-981 ◽

Cited By ~ 17

Author(s):

B W Lubit

Keyword(s):

Acetylcholine Receptor ◽

Acetylcholine Receptors ◽

Neuromuscular Junctions ◽

Morphological Changes ◽

Muscle Cells ◽

High Concentration ◽

Rat Muscle ◽

Cytoplasmic Actin ◽

High Concentrations

Previous immunocytochemical studies in which an antibody specific for mammalian cytoplasmic actin was used showed that a high concentration of cytoplasmic actin exists at neuromuscular junctions of rat muscle fibers such that the distribution of actin corresponded exactly to that of the acetylcholine receptors. Although clusters of acetylcholine receptors also are present in noninnervated rat and chick muscle cells grown in vitro, neither the mechanism for the formation and maintenance of these clusters nor the relationship of these clusters to the high density of acetylcholine receptors at the neuromuscular junction in vivo are known. In the present study, a relationship between beta-cytoplasmic actin and acetylcholine receptors in vitro has been demonstrated immunocytochemically using an antibody specific for the beta-form of cytoplasmic actin. Networks of cytoplasmic actin-containing filaments were found in discrete regions of the myotube membrane that also contained high concentrations of acetylcholine receptors; such high concentrations of acetylcholine receptors have been described in regions of membrane-substrate contact. Moreover, when primary rat myotubes were exposed to human myasthenic serum, gross morphological changes, accompanied by an apparent rearrangement of the cytoplasmic actin-containing cytoskeleton, were produced. Although whether the distribution of cytoplasmic actin-containing structures was influenced by the organization of acetylcholine receptor or vice versa cannot be determined from these studies, these findings suggest that in primary rat muscle cells grown in vitro, acetylcholine receptors and beta-cytoplasmic actin-containing structures may be somehow connected.

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