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. Using senescence-accelerated OXYS rats, which simulate key characteristics of sporadic AD, and Wistar rats (parental normal strain, control), we investigated hippocampal neurogenesis and glial changes during AD-like pathology. Using immunohistochemistry, we showed that the early stage of the pathology is accompanied by a lower intensity of neurogenesis and decreased astrocyte density in the dentate gyrus. The progressive stage is concurrent with reactive astrogliosis and microglia activation, as confirmed by increased cell densities and by the acquisition of cell-specific gene expression profiles, according to transcriptome sequencing data. Besides, here, we continued to analyze the anti-AD effects of prolonged supplementation with mitochondria-targeted antioxidant SkQ1. The antioxidant did not affect neurogenesis, partly normalized the gene expression profile of astrocytes and microglia, and shifted the resting/activated microglia ratio toward a decrease in the activated-cell density. In summary, both astrocytes and microglia are more vulnerable to AD-associated neurodegeneration in the CA3 area than in other hippocampal areas; SkQ1 had an anti-inflammatory effect and is a promising modality for AD prevention and treatment.

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. Four weeks after the cognitive training, we immunohistochemically estimated densities of quiescent and amplifying neuronal progenitors, neuronal-lineage cells (neuroblasts and immature and mature neurons), and astrocytes in young and adult rats, and the amyloid precursor protein and amyloid-ß in adult rats. Reference memory was defective in OXYS rats. The cognitive training did not affect neuronal-lineage cells' density in either rat strain either at the young or adult age, but activated neuronal progenitors in young rats and increased astrocyte density and downregulated amyloid-ß in adult OXYS rats. Thus, to activate adult neurogenesis, cognitive training should be started before first neurodegenerative changes, whereas cognitive training accompanying amyloid-ß accumulation affects only astrocytic support.

Effect of Abscisic Acid on Growth, Fatty Acid Profile, and Pigment Composition of the Chlorophyte Chlorella (Chromochloris) zofingiensis and Its Co-Culture Microbiome.

Microalga Chlorella (Chromochloris) zofingiensis has been gaining increasing attention of investigators as a potential competitor to Haematococcus pluvialis for astaxanthin and other xanthophylls production. Phytohormones, including abscisic acid (ABA), at concentrations relevant to that in hydroponic wastewater, have proven themselves as strong inductors of microalgae biomass productivity and biosynthesis of valuable molecules. The main goal of this research was to evaluate the influence of phytohormone ABA on the physiology of C. zofingiensis in a non-aseptic batch experiment. Exogenous ABA stimulated C. zofingiensis cell division, biomass production, as well as chlorophyll, carotenoid, and lipid biosynthesis. The relationship between exogenous ABA concentration and the magnitude of the observed effects was non-linear, with the exception of cell growth and biomass production. Fatty acid accumulation and composition depended on the concentration of ABA tested. Exogenous ABA induced spectacular changes in the major components of the culture microbiome of C. zofingiensis. Thus, the abundance of the representatives of the genus Rhodococcus increased drastically with an increase in ABA concentration, whereas the abundance of the representatives of Reyranella and Bradyrhizobium genera declined. The possibilities of exogenous ABA applications for the enhancing of the biomass, carotenoid, and fatty acid productivity of the C. zofingiensis cultures are discussed.

Effect of 17ß-Estradiol on Growth and Biosynthesis of Microalgae Scenedesmus quadricauda (CPCC-158) and Duckweed Lemna minor (CPCC-490) Grown in Three Different Media.

As fish farm wastewaters have detectable levels of fish hormones, such as 17ß-estradiol (E2), an understanding of the influence of fish steroids on algal (Scenedesmus quadricauda) and duckweed (Lemna minor) physiology is relevant to the potential use of fishery wastewaters for microalgae and plant biomass production. The study was conducted using three types of media: Bold Basal Medium (BBM), natural fishery wastewater (FWW), and reconstituted fishery wastewater (RFWW) with the nutrient composition adjusted to mimic FWW. During the experiment, the media were aerated and changes in the pH and conductivity of the water were closely monitored. E2 promoted the growth of S. quadricauda and L. minor, with significant accumulation of high-value biomolecules at very low steroid concentrations. However, clear differences in growth performance were observed in both test cultures, S. quadricauda and L. minor, grown in different media, and the most effective hormone concentrations were evidently different for the algae and the plant.

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. Therefore, we investigated the development of the most AD-affected brain structures (hippocampus and prefrontal cortex) using an immunohistochemical approach in senescence-accelerated OXYS rats, which are considered a suitable model of the most common-sporadic-type of AD. We noticed an additional peak of neurogenesis, which coincides in time with the peak of apoptosis in the hippocampus of OXYS rats on postnatal day three. Besides, we showed signs of delayed migration of neurons to the prefrontal cortex as well as disturbances in astrocytic and microglial support of the hippocampus and prefrontal cortex during the first postnatal week. Altogether, our results point to dysmaturation during early development of the brain-especially insufficient glial support-as a possible "first hit" leading to neurodegenerative processes and AD pathology manifestation later in life.

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. Here, we hypothesized that specific features of early postnatal brain development may be considered some of the prerequisites of AD development at an advanced age. To test this hypothesis, we used OXYS rats, which are a suitable model of sporadic AD. The duration of gestation, litter size, and weight at birth were lower in OXYS rats compared to control Wistar rats. The shortened duration of gestation may result in developmental retardation. Indeed, we noted decreased locomotor activity and increased anxiety in OXYS rats already at a young age: possible signs of altered brain development. We demonstrated retardation of the peak of postnatal neurogenesis in the hippocampal dentate gyrus of OXYS rats. Delayed neuronal maturation led to alterations of mossy-fiber formation: a shortened suprapyramidal bundle and longer infrapyramidal bundle, less pronounced fasciculation of granule cells' axons, and smaller size and irregular shape of nuclei in the CA3 pyramidal layer. These changes were accompanied by altered astrocytic migration. The observed features of early development may be considered some of the risk factors of the AD-like pathology that manifests itself in OXYS rats late in life.

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. Here, using OXYS rats as a suitable model of the most common (sporadic) form of AD, we examined neurogenesis in the hippocampal dentate gyrus in early ontogenesis prior to appearance of any signs of neurodegeneration and during development and progression of AD-like pathology. We demonstrated retardation of hippocampal development in OXYS rats at an early age; this problem may contribute to the emergence of AD signs late in life. Manifestation and progression of AD-like pathology are accompanied by transcriptome changes affecting genes involved in neurogenesis in the hippocampus. These genes are associated with the extracellular matrix and angiogenesis; this observation points to alteration of a cellular microenvironment. This change along with an increased TrkA/p75NTR ratio of nerve growth factor receptors in the hippocampus may contribute to increased density of immature neurons that we observed at the progressive stage of AD-like pathology in OXYS rats. These changes may be considered a compensatory reaction intended to slow down AD-associated neurodegeneration at the progressive stage of the disease. Collectively, these data suggest that alterations of neurogenesis may not only accompany the course of Alzheimer's disease but also play a causative role in this disorder.

Macrophytes may not contribute significantly to removal of nutrients, pharmaceuticals, and antibiotic resistance in model surface constructed wetlands.

Outdoor shallow wetland mesocosms, designed to simulate surface constructed wetlands to improve lagoon wastewater treatment, were used to assess the role of macrophytes in the dissipation of wastewater nutrients, selected pharmaceuticals, and antibiotic resistance genes (ARGs). Specifically, mesocosms were established with or without populations of Typha spp. (cattails), Myriophyllum sibiricum (northern water milfoil), and Utricularia vulgaris (bladderwort). Following macrophyte establishment, mesocosms were seeded with ARG-bearing organisms from a local wastewater lagoon, and treated with a single pulse of artificial municipal wastewater with or without carbamazepine, clofibric acid, fluoxetine, and naproxen (each at 7.6µg/L), as well as sulfamethoxazole and sulfapyridine (each at 150µg/L). Rates of pharmaceutical dissipation over 28d ranged from 0.073 to 3.0d(-1), corresponding to half-lives of 0.23 to 9.4d. Based on calculated rate constants, observed dissipation rates were consistent with photodegradation driving clofibric acid, naproxen, sulfamethoxazole, and sulfapyridine removal, and with sorption also contributing to carbamazepine and fluoxetine loss. Of the seven gene determinants assayed, only two genes for both beta-lactam resistance (blaCTX and blaTEM) and sulfonamide resistance (sulI and sulII) were found in sufficient quantity for monitoring. Genes disappeared relatively rapidly from the water column, with half-lives ranging from 2.1 to 99d. In contrast, detected gene levels did not change in the sediment, with the exception of sulI, which increased after 28d in pharmaceutical-treated systems. These shallow wetland mesocosms were able to dissipate wastewater contaminants rapidly. However, no significant enhancement in removal of nutrients or pharmaceuticals was observed in mesocosms with extensive aquatic plant communities. This was likely due to three factors: first, use of naïve systems with an unchallenged capacity for nutrient assimilation and contaminant removal; second, nutrient sequestration by ubiquitous filamentous algae; and third, dominance of photolytic processes in the removal of pharmaceuticals, which overshadowed putative plant-related processes.