New review on virus-like particles produced by neurons in seizures.

Frontiers in Neurology

https://www.frontiersin.org/articles/10.3389/fneur.2023.1201104/full

Arc protein, a remnant of ancient retrovirus, forms virus-like particles, which are abundantly generated by neurons during epileptic seizures, and affects epileptic susceptibility in rodent models.

Dmitry A. Sibarov, Vassiliy Tsytsarev, Anna Volnova, Anastasia N. Vaganova, Janaina Alves, Legier Rojas, Priscila Sanabria, Alla Ignashchenkova, Elton D. Savage and Mikhail Inyushin

Abstract

A product of the immediate early gene Arc (Activity-regulated cytoskeleton-associated protein or Arc protein) of retroviral ancestry resides in the genome of all tetrapods for millions of years and is expressed endogenously in neurons. It is a well-known protein, very important for synaptic plasticity and memory consolidation. Activity-dependent Arc expression concentrated in glutamatergic synapses affects the long-time synaptic strength of those excitatory synapses. Because it modulates excitatory-inhibitory balance in a neuronal network, the Arc gene itself was found to be related to the pathogenesis of epilepsy. General Arc knockout rodent models develop a susceptibility to epileptic seizures. Because of activity dependence, synaptic Arc protein synthesis also is affected by seizures. Interestingly, it was found that Arc protein in synapses of active neurons self-assemble in capsids of retrovirus-like particles, which can transfer genetic information between neurons, at least across neuronal synaptic boutons. Released Arc particles can be accumulated in astrocytes after seizures. It is still not known how capsid assembling and transmission timescale is affected by seizures. This scientific field is relatively novel and is experiencing swift transformation as it grapples with difficult concepts in light of evolving experimental findings. We summarize the emergent literature on the subject and also discuss the specific rodent models for studying Arc effects in epilepsy. We summarized both to clarify the possible role of Arc-related pseudo-viral particles in epileptic disorders, which may be helpful to researchers interested in this growing area of investigation.

Review on visible light reflection

Multilayer subwavelength gratings or sandwiches with periodic structure shape light reflection in the tapetum lucidum of taxonomically diverse vertebrate animals

Lidia Zueva, Astrid Zayas-Santiago, Legier Rojas, Priscila Sanabria, Janaina Alves, Vassiliy Tsytsarev, Mikhail Inyushin https://onlinelibrary.wiley.com/doi/full/10.1002/jbio.202200002

Abstract

Eye shine in the dark has attracted many researchers to the field of eye optics, but the initial studies of subwavelength arrangements in tapetum began only with the development of electronic microscopy at the end of the 20th century. As a result of a number of studies, it was shown that the reflective properties of the tapetum are due to their specialized cellular subwavelength microstructure (photonic crystals). These properties, together with the mutual orientation of the crystals, lead to a significant increase in reflection, which, in turn, enhances the sensitivity of the eye. In addition, research confirmed that optical mechanisms of reflection in the tapetum are very similar even for widely separated species. Due to progress in the field of nano-optics, researchers now have a better understanding of the main principles of this phenomenon. In this review, we summarize electron microscopic and functional studies of tapetal structures in the main vertebrate classes. This allows data on the microstructure of the tapetum to be used to improve our understanding of the visual system

Beta-amyloid and breast cancer tumor

Accumulation of amyloid beta (Aβ) and amyloid precursor protein (APP) in tumors formed by a mouse xenograft model of inflammatory breast cancer

 Astrid Zayas-Santiago , Michelle M Martínez-Montemayor , Jadier Colón-Vázquez , Gabriela Ortiz-Soto , Jose G Cirino-Simonet , Mikhail Inyushin

Abstract
Accumulation of amyloid in breast cancer is a well-known phenomenon, but only immunoglobulin light-chain amyloidosis (AL) or transthyretin (TTR) amyloid had been detected in human breast tumor samples previously. We recently reported that another amyloidogenic peptide, amyloid beta (Aβ), is present in an aggregated form in animal and human high-grade gliomas and suggested that it originates systemically from the blood, possibly generated by platelets. To study whether breast cancers are also associated with these Aβ peptides and in what form, we used a nude mouse model inoculated with triple-negative inflammatory breast cancer cell (SUM-149) xenografts, which develop noticeable tumors. Immunostaining with two types of specific antibodies for Aβ identified the clear presence of Aβ peptides associated with (a) carcinoma cells and (b) extracellular aggregated amyloid (also revealed by Congo red and thioflavin S staining). Aβ peptides, in both cells and in aggregated amyloid, were distributed in clear gradients, with maximum levels near blood vessels. We detected significant presence of amyloid precursor protein (APP) in the walls of blood vessels of tumor samples, as well as in carcinoma cells. Finally, we used ELISA to confirm the presence of elevated levels of mouse-generated Aβ40 in tumors. We conclude that Aβ in inflammatory breast cancer tumors, at least in a mouse model, is always present and is concentrated near blood vessels. We also discuss here the possible pathways of Aβ accumulation in tumors and whether this phenomenon could represent the specific signature of high-grade cancers.

New review on beta-amyloid

On the Role of Platelet-Generated Amyloid Beta Peptides in Certain Amyloidosis Health Complications

Mikhail Inyushin, Astrid Zayas-Santiago, Legier Rojas and Lilia Kucheryavykh

As do many other immunity-related blood cells, platelets release antimicrobial peptides that kill bacteria, fungi, and even certain viruses. Here we review the literature suggesting that there is a similarity between the antimicrobials released by other blood cells and the amyloid-related Aβ peptide released by platelets. Analyzing the literature, we also propose that platelet-generated Aβ amyloidosis may be more common than currently recognized. This systemic Aβ from a platelet source may participate in various forms of amyloidosis in pathologies ranging from brain cancer, glaucoma, skin Aβ accumulation, and preeclampsia to Alzheimer’s disease and late-stage Parkinson’s disease. We also discuss the advantages and disadvantages of specific animal models for studying platelet-related Aβ. This field is undergoing rapid change, as it evaluates competing ideas in the light of new experimental observations. We summarized both in order to clarify the role of platelet-generated Aβ peptides in amyloidosis-related health disorders, which may be helpful to researchers interested in this growing area of investigation.

New research of beta-amyloid

Accumulation of amyloid beta in human glioblastomas

A. Zayas‐Santiago, A. Díaz‐García , R. Nuñez‐Rodríguez, M. Inyushin https://onlinelibrary.wiley.com/doi/abs/10.1111/cei.13493

Clinical & Experimental Immunology

Abstract
Many cancer types are intrinsically associated with specific types of amyloidosis, in which amyloidis accumulated locally inside tumors or systemically. Usually, this condition relates to the hyper-production of specific amylogenic proteins. Recently, we found that the accumulation of amyloid beta (Aβ) peptide immunofluorescence is linked to glioma cells in mouse tumors. Here we report that amyloid-specific histochemical dyes reveal amyloid accumulation in all human glioma samples. Application of two different antibodies against Aβ peptide (a polyclonal antibody against human Aβ1-42 and a monoclonal pan-specific MOAB-2 antibody against Aβ) showed that the amyloid in glioma samples contains Aβ. Amyloid was linked to glioma cells expressing glial-specific fibrillary acidic protein (GFAP) and to glioma blood vessels. Astrocytes close to the glioma site and to affected vessels also accumulated Aβ. We discuss whether amyloid is produced by glioma cells or is the result of systemic production of Aβ in response to glioma development due to an innate immunity reaction. We conclude that amyloid buildup in glioma tumors is a part of the tumor environment and may be used as a target for developing a novel class of antitumor drugs and as an antigen for glioma visualization.

Research on beta-amyloid in stroke

Accumulation of Amyloid Beta (Aβ) Peptide on Blood Vessel Walls in the Damaged Brain after Transient Middle Cerebral Artery Occlusion

Antonio Henrique Martins , Astrid Zayas-Santiago, Yancy Ferrer-Acosta , Solianne M. Martinez-Jimenez , Lidia Zueva , Amanda Diaz-Garcia and Mikhail Inyushin

Abstract

It is well known that amyloid beta (Aβ) peptides are generated in blood vessels, released into the brain during thrombosis, and temporarily accumulate in this organ after injury. Here we demonstrate that 24 h after transient middle cerebral artery occlusion (tMCAO), one of the standard models of focal ischemic stroke, Aβ peptide accumulates in the brain, concentrating on the blood vessel walls. Because Aβ oligomers are known to induce significant damage to brain cells, they act as an additional damaging factor during ischemic stroke. Considering that they have been shown to form ion channels in cells, affecting osmotic balance, we used an Aβ peptide channel blocker, tromethamine (2-amino-2-(hydroxymethyl) propane-1,3-diol), to prevent this additional injury. Tromethamine injected 0.1 g/100 g body weight intraperitoneally at 5 min before tMCAO decreased water content in the damaged hemisphere, as measured by dry brain weight. Congo red staining, which binds only to Aβ oligomer plaques (amyloid), showed that there was no significant presence of plaques. Therefore, we suggest that Aβ peptide oligomers are responsible for some of the brain damage during stroke and that blockage of the ion channels that they form could be beneficial in treating this complex neurological syndrome.

New research on transparency

Tissue Transparency In Vivo

Mikhail Inyushin , Daria Meshalkina , Lidia Zueva , and Astrid Zayas-Santiago

https://www.mdpi.com/1420-3049/24/13/2388

Abstract

In vivo tissue transparency in the visible light spectrum is beneficial for many research applications that use optical methods, whether it involves in vivo optical imaging of cells or their activity, or optical intervention to affect cells or their activity deep inside tissues, such as brain tissue. The classical view is that a tissue is transparent if it neither absorbs nor scatters light, and thus absorption and scattering are the key elements to be controlled to reach the necessary transparency. This review focuses on the latest genetic and chemical approaches for the decoloration of tissue pigments to reduce visible light absorption and the methods to reduce scattering in live tissues. We also discuss the possible molecules involved in transparency.

Research on beta-amyloid:

Accumulation of Innate Amyloid Beta Peptide in Glioblastoma Tumors

L.Y. Kucheryavykh , J. Ortiz-Rivera , Y. V. Kucheryavykh , A. Zayas-Santiago, A. Diaz-Garcia and M.Y. Inyushin

Immunostaining with specific antibodies has shown that innate amyloid beta (Aβ) is accumulated naturally in glioma tumors and nearby blood vessels in a mouse model of glioma. In immunofluorescence images, Aβ peptide coincides with glioma cells, and enzyme-linked immunosorbent assay (ELISA) have shown that Aβ peptide is enriched in the membrane protein fraction of tumor cells. ELISAs have also confirmed that the Aβ(1–40) peptide is enriched in glioma tumor areas relative to healthy brain areas. Thioflavin staining revealed that at least some amyloid is present in glioma tumors in aggregated forms. We may suggest that the presence of aggregated amyloid in glioma tumors together with the presence of Aβ immunofluorescence coinciding with glioma cells and the nearby vasculature imply that the source of Aβ peptides in glioma can be systemic Aβ from blood vessels, but this question remains unresolved and needs additional studies.

Review: Platelet-generated amyloid beta peptides in Alzheimer’s disease and glaucoma.

Inyushin M, Zayas-Santiago A, Rojas L, Kucheryavykh Y, Kucheryavykh L

Amyloid beta (Aβ) peptides have been implicated in both Alzheimer’s disease (AD) and glaucoma and have been shown to be the key etiological factor in these dangerous health complications. On the other hand, it is well known that Aβ peptide can be generated from its precursor protein and massively released from the blood to nearby tissue upon the activation of platelets due to their involvement in innate immunity and inflammation processes. Here we review evidence about the development of AD and glaucoma neuronal damage showing their dependence on platelet count and activation. The correlation between the effect on platelet count and the effectiveness of anti-AD and anti-glaucoma therapies suggest that platelets may be an important player in these diseases.

Research on transparency


Localization of αA-Crystallin in Rat Retinal Müller Glial Cells and Photoreceptors.

Zayas-Santiago A, Ríos DS, Zueva LV, Inyushin MY.

Transparent cells in the vertebrate optical tract, such as lens fiber cells and corneal epithelium cells, have specialized proteins that somehow permit only a low level of light scattering in their cytoplasm. It has been shown that both cell types contain (1) beaded intermediate filaments as well as (2) α-crystallin globulins. It is known that genetic and chemical alterations to these specialized proteins induce cytoplasmic opaqueness and visual complications. Crystallins were described previously in the retinal Müller cells of frogs. In the present work, using immunocytochemistry, fluorescence confocal imaging, and immuno-electron microscopy, we found that αA-crystallins are present in the cytoplasm of retinal Müller cells and in the photoreceptors of rats. Given that Müller glial cells were recently described as “living light guides” as were photoreceptors previously, we suggest that αA-crystallins, as in other highly transparent cells, allow Müller cells and photoreceptors to minimize intraretinal scattering during retinal light transmission.

KEYWORDS:
Müller cells; crystallins; immunogold; retina; transparency

Research on beta-amyloid

Amyloid Beta Peptide Is Released during Thrombosis in the Skin.  

Kucheryavykh LY, Kucheryavykh YV, Washington AV, Inyushin MY.

Abstract
While it is known that amyloid beta (Aβ) deposits are found in different tissues of both Alzheimer’s disease (AD) patients and healthy individuals, there remain questions about the physiological role of these deposits, the origin of the Aβ peptide, and the mechanisms of its localization to the tissues. Using immunostaining with specific antibodies, as well as enzyme-linked immunosorbent assay, this study demonstrated Aβ40 peptide accumulation in the skin during local experimental photothrombosis in mice. Specifically, Aβ peptide accumulation was concentrated near the dermal blood vessels in thrombotic skin. It was also studied whether the released peptide affects microorganisms. Application of Aβ40 (4 µM) to the external membrane of yeast cells significantly increased membrane conductance with no visible effect on mouse host cells. The results suggest that Aβ release in the skin is related to skin injury and thrombosis, and occurs along with clotting whenever skin is damaged. These results support the proposition that Aβ release during thrombosis serves as part of a natural defense against infection.

KEYWORDS:
Aβ40 peptide; natural peptide antibiotic; skin; thrombosis