Physiological and transcriptomic analysis reveals the toxicological mechanisms of polystyrene micro- and nano-plastics in Chlamydomonas reinhardtii.

With the accumulation of plastic waste in the environment, the toxicity of micro- and nano-plastics (MNPs) to microalgae has attracted increasing attention. However, the underlying toxic mechanisms of MNPs remain to be elucidated. In this study, we synthesized micro- and nano-scale of polystyrene MNPs (PS MNPs) to investigate their toxicity and toxic mechanisms in Chlamydomonas reinhardtii. We found that PS MNPs significantly inhibit the production of photosynthetic pigments and increase soluble protein content. The detailed analysis of results shows that both materials affect photosynthetic efficiency by damaging the donor side, reaction center, and electron transfer of photosystem II. Moreover, compared to PS MPs, PS NPs have a greater negative impact on algal cells. Analyzing the transcriptome of cells suggests that the most sensitive metabolic pathways in response to PS MNPs involve oxidative phosphorylation, biosynthesis of secondary metabolites, and photosynthesis. Especially, genes related to photosynthesis and oxidative phosphorylation showed significant changes in expression after exposure to PS MNPs. This study provided molecular-level insights into the toxic mechanisms of PS MNPs on microalgae.

D-serine reconstitutes synaptic and intrinsic inhibitory control of pyramidal neurons in a neurodevelopmental mouse model for schizophrenia.

The hypothesis of N-methyl-D-aspartate receptor (NMDAR) dysfunction for cognitive impairment in schizophrenia constitutes the theoretical basis for the translational application of NMDAR co-agonist D-serine or its analogs. However, the cellular mechanism underlying the therapeutic effect of D-serine remains unclear. In this study, we utilize a mouse neurodevelopmental model for schizophrenia that mimics prenatal pathogenesis and exhibits hypoexcitability of parvalbumin-positive (PV) neurons, as well as PV-preferential NMDAR dysfunction. We find that D-serine restores excitation/inhibition balance by reconstituting both synaptic and intrinsic inhibitory control of cingulate pyramidal neurons through facilitating PV excitability and activating small-conductance Ca2+-activated K+ (SK) channels in pyramidal neurons, respectively. Either amplifying inhibitory drive via directly strengthening PV neuron activity or inhibiting pyramidal excitability via activating SK channels is sufficient to improve cognitive function in this model. These findings unveil a dual mechanism for how D-serine improves cognitive function in this model.

Environmental Enrichment Improves the Recognition Memory in Adult Mice Following Social Isolation via Downregulation of Kv4.2 Potassium Channels.

Recognition memory is a cognitive process that enables us to distinguish familiar objects and situations from new items, which is essential for mammalian survival and adaptation to a changing environment. Social isolation (SI) has been implicated as a detrimental factor for recognition memory. The medial prefrontal cortex (mPFC) has been shown to carry information concerning the relative familiarity of individual stimuli, and modulating neuronal function in this region may contribute to recognition memory. The present study aimed to investigate the neuronal mechanisms in the mPFC of environmental enrichment (EE) on recognition memory in adult mice following SI. Mice were assigned into three groups: control, SI, and SI + EE groups. Novel location recognition (NLR) and novel object recognition (NOR) tests were performed to evaluate the recognition memory. The levels of Kv4 channels were assessed by qRT-PCR and western blotting. The effects of SI and SI + EE on the excitability of pyramidal neurons in the mPFC were measured using whole-cell recording. We found that SI led to a reduction in the excitability of pyramidal neurons. Specifically, we have identified that the reduction in the firing activity of pyramidal neurons resulted from alterations in the function and expression of Kv4.2 channels. Furthermore, EE regulated Kv4.2 channels, normalized the activity of pyramidal neurons, and restored the behavioral deficits following SI. Thus, the roles of Kv4.2 channels in excitability of pyramidal neurons suggest that the Kv4.2 channels present a promising therapeutic target for recognition memory impairment.

Transcriptome analysis reveals the molecular mechanisms by which carbon dots regulate the growth of Chlamydomonas reinhardtii.

Carbon dots (CDs) have attracted increasing attention for their ability to artificially improve photosynthesis. Microalgal bioproducts have emerged as promising sources of sustainable nutrition and energy. However, the gene regulation mechanism of CDs on microalgae remains unexplored. The study synthesized red-emitting CDs and applied them to Chlamydomonas reinhardtii. Results showed that 0.5 mg/L-CDs acted as light supplements to promote cell division and biomass in C. reinhardtii. CDs improved the energy transfer of PS II, photochemical efficiency of PS II, and photosynthetic electron transfer. The pigment content and carbohydrate production slightly increased, while protein and lipid contents significantly increased (by 28.4% and 27.7%, respectively) in a short cultivation time. Transcriptome analysis identified 1166 differentially expressed genes. CDs resulted in faster cell growth by up-regulating the expression of genes associated with cell growth and death, promoting sister chromatid separation, accelerating the mitotic process and shortening the cell cycle. CDs improved the ability of energy conversion by up-regulating photosynthetic electron transfer-related genes. Carbohydrate metabolism-related genes were regulated and provided more available pyruvate for the citrate cycle. The study provides evidence for the genetic regulation of microalgal bioresources by artificially synthesized CDs.

PPARα is involved in high-fat diet-induced risk avoidance impairment via the regulation of hippocampal BDNF.

Risk avoidance behaviors are essential for survival. "Uncontrollable" risk-taking behaviors in animals or humans may have severe adverse consequences. In humans, a large proportion of psychiatric disorders are accompanied by impairments in risk avoidance. Obesity is associated with psychiatric disorders. Peroxisome proliferator-activated receptor α (PPARα) takes part in regulating lipid metabolism and neuronal function. Here, we investigated the effect of high-fat diet (HFD)-induced obesity on risk avoidance and the role of PPARα in this behavior. Male PPARα-null (KO) mice and wild-type (WT) mice were assigned to four different groups: WT-CON and KO-CON (normal diet); WT-HFD and KO-HFD (high fat diet). The HFD began at week 6 and was continued until sampling. A series of behavioral tests were performed at week 11. We found that WT but not KO mice fed with a HFD exhibited weight gain and risk avoidance impairment, compared with the mice fed with a normal diet. The staining of c-Fos revealed that the hippocampus was the main brain region involved in risk avoidance behavior. Moreover, biochemical analysis suggested that the decreased levels of the brain-derived neurotrophic factor (BDNF) in the hippocampus might contribute to risk avoidance impairment induced by a HFD. These results indicated that PPARα is involved in HFD-induced risk avoidance impairment via the regulation of hippocampal BDNF.

Lateral septal nucleus, dorsal part, and dentate gyrus are necessary for spatial and object recognition memory, respectively, in mice.

Introduction: Cognitive impairment includes the abnormality of learning, memory and judgment, resulting in severe learning and memory impairment and social activity impairment, which greatly affects the life quality of individuals. However, the specific mechanisms underlying cognitive impairment in different behavioral paradigms remain to be elucidated. Methods: The study utilized two behavioral paradigms, novel location recognition (NLR) and novel object recognition (NOR), to investigate the brain regions involved in cognitive function. These tests comprised two phases: mice were presented with two identical objects for familiarization during the training phase, and a novel (experiment) or familiar (control) object/location was presented during testing. Immunostaining quantification of c-Fos, an immediate early gene used as a neuronal activity marker, was performed in eight different brain regions after the NLR or NOR test. Results: The number of c-Fos-positive cells was significantly higher in the dorsal part of the lateral septal nucleus (LSD) in the NLR and dentate gyrus (DG) in the NOR experiment group than in the control group. We further bilaterally lesioned these regions using excitotoxic ibotenic acid and replenished the damaged areas using an antisense oligonucleotide (ASO) strategy. Discussion: These data reinforced the importance of LSD and DG in regulating spatial and object recognition memory, respectively. Thus, the study provides insight into the roles of these brain regions and suggests potential intervention targets for impaired spatial and object recognition memory.

Biocidal H2O2 treatment emphasizes the crucial role of cyanobacterial extracellular polysaccharides against external strong oxidative stress.

A biocidal level of hydrogen peroxide (H2O2), far beyond the natural level, is widely used to control bloom-forming cyanobacteria in freshwater. The extracellular polymeric substance of these cyanobacteria is a key factor in determining the applied H2O2 dosage. The exopolysaccharide (EPS) in the extracellular polymer shows H2O2 scavenging capability. However, the scavenging capabilities of EPSs from other cyanobacteria against biocidal levels of H2O2 as well as their protective roles against cyanobacterial cells are not well known. In this study, we used four nonbloom-forming cyanobacteria as target organisms, two with rich EPS envelopes (EPS-rich strains) and two with thin EPS envelopes (EPS-thin strains), to assess the roles of EPS. It was found that the two EPS-rich strains were much more tolerant to a high dose of exogenous H2O2 than the two EPS-thin strains. The EPSs extracted from the four strains exhibited similar but rapid H2O2 scavenging activity. Additionally, the EPSs from the EPS-rich strains could improve the tolerance of the EPS-thin strains to H2O2 stress, implying potentially nonselective protection against oxidative stress. In addition, all the cell lysates of the four strains showed H2O2 decomposition ability, with the efficiency being slightly different between the two types of strains. This study suggests that cyanobacterial EPS plays a generally crucial role against external strong oxidative stress and may provide a useful reference for the application of H2O2 in environmental management.

Carbon nanomaterial-treated cell cultures of Nostoc flagelliforme produce exopolysaccharides with ameliorative physio-chemical properties.

The feasibility and efficiency of carbon nanomaterials (CNMs) in algal biotechnology are less known. In this study, the influences of four CNMs, graphene (G), graphene oxide (GO), multiwalled carbon nanotube (MWCNT), and aminated multiwalled carbon nanotube (MWCNT-NH2), on cell growth and exopolysaccharide (EPS) production, as well as the physiochemical properties of EPS, were investigated in cell culture of Nostoc flagelliforme. A proper concentration (15 mg L-1) of four CNMs was chosen for use after a preliminary test. Upon GO treatment, the biomass was improved by 11.1 % and the EPS production was increased by 36.1 % on day 16 compared to the nontreated control. Four CNM treatments significantly improved cellular O2·- and H2O2 levels as well as superoxide dismutase and catalase activities. The monosaccharide compositions and functional groups of the EPSs were obviously altered by the CNM treatments. Particularly, the GO treatment-resulting EPS showed obviously improved flocculating ability, water absorption ability, and reactive oxygen species scavenging ability. In general, four CNMs exerted distinct influences on the production and physio-chemical property alteration of the EPS in N. flagelliforme culture. This work expands our understanding of the application of CNMs in the induced production and functional modification of polysaccharides during algal cultivation.

Deficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer's Disease.

The N-methyl-D-aspartate receptor is a critical molecule for synaptic plasticity and cognitive function. Impaired synaptic plasticity is thought to contribute to the cognitive impairment associated with Alzheimer's disease (AD). However, the neuropathophysiological alterations of N-methyl-D-aspartate receptor (NMDAR) function and synaptic plasticity in hippocampal CA1 in transgenic rodent models of AD are still unclear. In the present study, APP/PS1 mice were utilized as a transgenic model of AD, which exhibited progressive cognitive impairment including defective working memory, recognition memory, and spatial memory starting at 6 months of age and more severe by 8 months of age. We found an impaired long-term potentiation (LTP) and reduced NMDAR-mediated spontaneous excitatory postsynaptic currents (sEPSCs) in the hippocampal CA1 of APP/PS1 mice with 8 months of age. Golgi staining revealed that dendrites of pyramidal neurons had shorter length, fewer intersections, and lower spine density in APP/PS1 mice compared to control mice. Further, the reduced expression levels of NMDAR subunits, PSD95 and SNAP25 were observed in the hippocampus of APP/PS1 mice. These results suggest that NMDAR dysfunction, impaired synaptic plasticity, and disrupted neuronal morphology constitute an important part of the neuropathophysiological alterations associated with cognitive impairment in APP/PS1 mice.