Invisible but Insidious Effects of Microplastics.

Increasing evidence on the adverse health impacts of microplastics (MPs) is available, but their associated risks to the well-being of humans and long-term impacts are poorly understood. An indicator of the remote effects of MPs may be their influence on the rate of aging. To assess the effects of MPs on the aging process, we used accelerated senescence OXYS rats that develop a complex of geriatric diseases.

The Expression of Genes , , and in Distinct Regions of the Heart and Its Possible Contribution to the Development of Hypertension.

Background: It is believed that alterations in the functioning of the cytochrome P450 (CYP), which participates in metabolic transformations of endogenous polyunsaturated fatty acids (PUFAs) (with the formation of cardioprotective or cardiotoxic products), affects the development of age-related cardiovascular diseases and reduces the effectiveness of some cardioselective drugs. For example, CYP2J2 activation or CYP1B1 inhibition protects against the cardiovascular toxicity of anticancer drugs. It is currently unclear whether CYPs capable of metabolizing arachidonic acid and ω-3 PUFAs to vasodilatory and vasoconstrictive derivatives are expressed in all heart regions.

Changes in the Glutamate/GABA System in the Hippocampus of Rats with Age and during Alzheimer's Disease Signs Development.

GABA and glutamate are the most abundant neurotransmitters in the CNS and play a pivotal part in synaptic stability/plasticity. Glutamate and GABA homeostasis is important for healthy aging and reducing the risk of various neurological diseases, while long-term imbalance can contribute to the development of neurodegenerative disorders, including Alzheimer's disease (AD). Normalization of the homeostasis has been discussed as a promising strategy for prevention and/or treatment of AD, however, data on the changes in the GABAergic and glutamatergic systems with age, as well as on the dynamics of AD development, are limited.

Amisulpride Decreases Tau Protein Hyperphosphorylation in the Brain of OXYS Rats.

Aim: In this study, OXYS rats of three ages (1, 3, and 6 months), a proven model of Alzheimer's disease (AD), at various stages of disease progression were used to thoroughly study the effects of amisulpride on behavior and tau protein phosphorylation.

Background: With the growing number of patients with AD, the problem of finding a cure is very acute. Neurodegeneration in AD has various causes, one of which is hyperphosphorylation of tau protein.

SkQ1 as a Tool for Controlling Accelerated Senescence Program: Experiments with OXYS Rats.

According to the concept suggested by V. P. Skulachev and co-authors, aging of living organisms can be considered as a special case of programmed death of an organism - phenoptosis, and mitochondrial antioxidant SkQ1 is capable of inhibiting both acute and chronic phenoptosis (aging).

The Rat Brain Transcriptome: From Infancy to Aging and Sporadic Alzheimer's Disease-like Pathology.

It has been suggested that functional traits of the adult brain-all of which are established early in life-may affect the brain's susceptibility to Alzheimer's disease (AD). Results of our previous studies on senescence-accelerated OXYS rats, a model of sporadic AD, support this hypothesis. Here, to elucidate the molecular genetic nature of the aberrations revealed during brain maturation, we analyzed transcriptomes (RNA-seq data) of the prefrontal cortex (PFC) and hippocampus of OXYS rats and Wistar (control) rats in the period of brain maturation critical for OXYS rats (ages P3 and P10; P: postnatal day).

Delayed Formation of Neonatal Reflexes and of Locomotor Skills Is Associated with Poor Maternal Behavior in OXYS Rats Prone to Alzheimer's Disease-like Pathology.

Postnatal brain development is characterized by high plasticity with critical windows of opportunity where any intervention may positively or adversely influence postnatal growth and lead to long-lasting consequences later in life. Poor maternal care is among these interventions. Here, we found that senescence-accelerated OXYS rats prone to an Alzheimer's disease-like pathology are characterized by more passive maternal behavior and insufficient care for pups as compared to control (Wistar) rats.

Changes in Glial Support of the Hippocampus during the Development of an Alzheimer's Disease-like Pathology and Their Correction by Mitochondria-Targeted Antioxidant SkQ1.

Astrocytes and microglia are the first cells to react to neurodegeneration, e.g., in Alzheimer's disease (AD); however, the data on changes in glial support during the most common (sporadic) type of the disease are sparse.

Glia Not Neurons: Uncovering Brain Dysmaturation in a Rat Model of Alzheimer's Disease.

Sporadic Alzheimer's disease (AD) is a severe disorder of unknown etiology with no definite time frame of onset. Recent studies suggest that middle age is a critical period for the relevant pathological processes of AD. Nonetheless, sufficient data have accumulated supporting the hypothesis of "neurodevelopmental origin of neurodegenerative disorders": prerequisites for neurodegeneration may occur during early brain development.

MEK1/2-ERK Pathway Alterations as a Therapeutic Target in Sporadic Alzheimer's Disease: A Study in Senescence-Accelerated OXYS Rats.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia worldwide, with no cure. There is growing interest in mitogen-activated protein kinases (MAPKs) as possible pathogenesis-related therapeutic targets in AD. Previously, using senescence-accelerated OXYS rats, which simulate key characteristics of the sporadic AD type, we have shown that prolonged treatment with mitochondria-targeted antioxidant plastoquinonyl-decyltriphenylphosphonium (SkQ1) during active progression of AD-like pathology improves the activity of many signaling pathways (SPs) including the p38 MAPK SP.

Cognitive Training as a Potential Activator of Hippocampal Neurogenesis in the Rat Model of Sporadic Alzheimer's Disease.

There is a growing body of evidence that interventions like cognitive training or exercises prior to the manifestation of Alzheimer's disease (AD) symptoms may decelerate cognitive decline. Nonetheless, evidence of prevention or a delay of dementia is still insufficient. Using OXYS rats as a suitable model of sporadic AD and Wistar rats as a control, we examined effects of cognitive training in the Morris water maze on neurogenesis in the dentate gyrus in presymptomatic (young rats) and symptomatic (adult rats) periods of development of AD signs.

SkQ1 Suppresses the p38 MAPK Signaling Pathway Involved in Alzheimer's Disease-Like Pathology in OXYS Rats.

Alzheimer's disease (AD) is the most common type of dementia and is currently incurable, and mitogen-activated protein kinase (MAPK) p38 is implicated in the pathogenesis of AD. p38 MAPK inhibition is considered a promising strategy against AD, but there are no safe inhibitors capable of penetrating the blood-brain barrier. Earlier, we have shown that mitochondria-targeted antioxidant plastoquinonyl-decyltriphenylphosphonium (SkQ1) at nanomolar concentrations can prevent, slow down, or partially alleviate AD-like pathology in accelerated-senescence OXYS rats.

Features of Postnatal Hippocampal Development in a Rat Model of Sporadic Alzheimer's Disease.

Aging is the major risk factor of the most common (∼95% of cases) sporadic Alzheimer's disease (AD). Accumulating data indicate middle age as a critical period for the relevant pathological processes, however, the question of when AD starts to develop remains open. It has been reported only recently that in the early postnatal period-when brain development is completing-preconditions for a decrease in cognitive abilities and for accelerated aging can form.

Suppression of Alzheimer's Disease-Like Pathology Progression by Mitochondria-Targeted Antioxidant SkQ1: A Transcriptome Profiling Study.

Alzheimer's disease (AD) is the most common type of dementia, with increasing prevalence and no disease-modifying treatment available yet. There is increasing evidence-from interventions targeting mitochondria-that may shed some light on new strategies for the treatment of AD. Previously, using senescence-accelerated OXYS rats that simulate key characteristics of sporadic AD, we have shown that treatment with mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) from age 12 to 18 months (that is, during active progression of AD-like pathology)-via improvement of mitochondrial function-prevented the neuronal loss and synaptic damage, enhanced neurotrophic supply, and decreased amyloid- protein levels and tau hyperphosphorylation in the hippocampus.

Alterations of hippocampal neurogenesis during development of Alzheimer's disease-like pathology in OXYS rats.

Neurogenesis is the key mechanism of neuronal plasticity in the adult mammalian brain. Alterations of neurogenesis happen concurrently with (and contribute to) development and progression of numerous neuropathological conditions including Alzheimer's disease (AD). Being the most common type of dementia, AD is studied extensively; however, the data concerning changes in neurogenesis in the pathogenesis of this disease are inconsistent.

The Rat Prefrontal-Cortex Transcriptome: Effects of Aging and Sporadic Alzheimer's Disease-Like Pathology.

Alzheimer's disease (AD) is the most widespread late-life dementia and involves the prefrontal cortex, a vulnerable brain region implicated in memory, emotion, cognition, and decision-making behavior. To understand the molecular differences between the effects of aging and AD on the prefrontal cortex, this study characterized the age-dependent changes in gene expression in Wistar rats (control) and OXYS rats (rodents that simulate key characteristics of sporadic AD) using RNA sequencing. We found that major altered biological processes during aging in Wistar rats were associated with immune processes.

p62 /SQSTM1 coding plasmid prevents age related macular degeneration in a rat model.

P62/SQSTM1, a multi-domain protein that regulates inflammation, apoptosis, and autophagy, has been linked to age-related pathologies. For example, previously we demonstrated that administration of p62/SQSTM1-encoding plasmid reduced chronic inflammation and alleviated osteoporosis and metabolic syndrome in animal models. Herein, we built upon these findings to investigate effect of the p62-encoding plasmid on an age-related macular degeneration (AMD), a progressive neurodegenerative ocular disease, using spontaneous retinopathy in senescence-accelerated OXYS rats as a model.

Mitochondrial Dysfunction as a Predictor and Driver of Alzheimer's Disease-Like Pathology in OXYS Rats.

Growing evidence suggests that mitochondrial dysfunction is an early event in sporadic Alzheimer's disease (AD), but the impact of mitochondrial dysfunction on the transition from healthy aging to AD remains elusive. Here we estimated the influence of mitochondrial dysfunction on the initiation of AD signs in OXYS rats, which simulate key characteristics of sporadic AD. We assessed the mitochondrial ultrastructure of pyramidal neurons of the hippocampus at the age preceding the development (age 20 days), during manifestation (4-5 months), and at the well-pronounced stages (18-24 months) of the AD-like pathology in OXYS rats.

Association of cerebrovascular dysfunction with the development of Alzheimer's disease-like pathology in OXYS rats.

Background: Cerebrovascular dysfunction plays a critical role in the pathogenesis of Alzheimer's disease (AD): the most common cause of dementia in the elderly. The involvement of neurovasculature disorders in the progression of AD is now increasingly appreciated, but whether they represent initial factors or late-stage pathological changes during the disease is unclear. Using senescence-accelerated OXYS rats, which simulate key characteristics of sporadic AD, we evaluated contributions of cerebrovascular alterations to the disease development.

An antioxidant specifically targeting mitochondria delays progression of Alzheimer's disease-like pathology.

Mitochondrial aberrations are observed in human Alzheimer's disease (AD) and in medical conditions that increase the risk of this disorder, suggesting that mitochondrial dysfunction may contribute to pathophysiology of AD. Here, using OXYS rats that simulate key characteristics of sporadic AD, we set out to determine the role of mitochondria in the pathophysiology of this disorder. OXYS rats were treated with a mitochondria-targeted antioxidant SkQ1 from age 12 to 18 months, that is, during active progression of AD-like pathology in these animals.

Efficacy of Mitochondrial Antioxidant Plastoquinonyl-decyl-triphenylphosphonium Bromide (SkQ1) in the Rat Model of Autoimmune Arthritis.

Rheumatoid arthritis is one of the most common autoimmune diseases. Many antioxidants have been tested in arthritis, but their efficacy was, at best, marginal. In this study, a novel mitochondria-targeted antioxidant, plastoquinonyl-decyl-triphenylphosphonium bromide (SkQ1), was tested in vivo to prevent and cure experimental autoimmune arthritis.

Melatonin Attenuates Memory Impairment, Amyloid-β Accumulation, and Neurodegeneration in a Rat Model of Sporadic Alzheimer's Disease.

Melatonin is a multifunctional molecule and plays a crucial role in the regulation of circadian rhythms. The role of melatonin in the protection of the central nervous system is well documented. Therefore, melatonin was proposed as a possible therapeutic agent for reducing the severity of Alzheimer's disease (AD), a progressive neurodegenerative disease characterized by cognitive decline and memory dysfunction.

Melatonin attenuates impairments of structural hippocampal neuroplasticity in OXYS rats during active progression of Alzheimer's disease-like pathology.

Translational research on Alzheimer's disease (AD) has often focused on reducing the high cerebral levels of amyloid-β (Aβ) as a key characteristic of AD pathogenesis. There is, however, a growing body of evidence that synaptic dysfunction may be crucial for the development of the most common (sporadic) form of AD. The applicability of melatonin (mainly produced by the pineal gland) to the treatment of AD is actively evaluated, but usually, such studies are based on animal models of early-onset AD, which is responsible for only ~5% of AD cases.