Impaired Learning Ability Research Articles

Role of RNA m6A reader YTHDF2 in neurodegeneration of the aged mice

Objective: To investigate the role of RNA m6A reader YTHDF2 in neurodegeneration of the aged mice. Methods: Eighteen 18-month-old control C57BL/6 mice and 22 Ythdf2 conditional knockout (cKO) mice of the same age (that exhibited significant aging characteristics) were used. Five pairs of mice were used for morphological analysis. Thirteen control mice and 17 cKO mice were used for behavioral experiments. Immunofluorescence analysis was performed to detect the expression of YTHDF2 in the brains of 18-month-old C57BL/6 mice. After establishing the neural progenitor cell-specific knockout mice of Ythdf2, their phenotypes were analyzed through comparison of body weight, brain weight and H&E staining. Subsequently, immunohistochemistry and immunofluorescence analyses were used to detect the expression of various neural cell-specific markers in the aged control mice and Ythdf2 cKO mice. Finally, behavioral tests, including the open field test, new object recognition, and water maze, were used to assess the levels of anxiety, depression, learning and memory abilities. Results: Immunofluorescence staining showed that YTHDF2 was mainly expressed in the neurons. Compared with the age-matched control mice, there was no significant change in the body weight of the Ythdf2 cKO mice, but the brain weight decreased significantly (P<0.05). The immunostaining showed that Ythdf2 cKO mice had fewer neurons, fewer astrocytes with defective morphology, more microglia and activation of microglia (P<0.05). Behavioral tests showed that the aged Ythdf2 cKO mice exhibited impaired movement, learning and memory abilities (P<0.05). Conclusions: YTHDF2 is mainly expressed in the neurons of the aged brain. Conditional knockout of Ythdf2 causes quantitative and structural abnormalities in hippocampal neuronal cells, and impairs motor ability and learning and memory of the aged mice, suggesting that YTHDF2 plays an important role in neurodegeneration of the aged mice.

Starvation impairs learning ability during development by regulating neurodevelopment-related genes in Caenorhabditis elegans

Controlling weight through starvation is a popular phenomenon among Chinese teenagers, according to our self-made questionnaire. However, the potential side effects on teenagers have not been clearly identified. In this research, C. elegans in developing age was utilised as a model organism to identify the impact of starvation on learning ability, including associative and non-associative learning. The impaired learning ability and changes in some essential physiological indicators were observed after starvation. Then, the change in the relative expression level of nine neurodevelopment-related genes affected by starvation was further investigated by RT-qPCR. The downregulation of eat-4 and the upregulation of casy-1 and tph-1 were detected after starvation. Furthermore, homology analysis revealed that the human homolog of eat-4 is SLC17A7/VGLUT1, suggesting a similar starvation mechanism in humans. In conclusion, this study demonstrated that starvation could impair the learning ability of C. elegans through the regulation of neurodevelopment-related genes.

Neonatal Maternal Separation Impairs Cognitive Function and Synaptic Plasticity in Adult Male CD-1 Mice

Maternal separation (MS) increases the risk of occurrence of anxiety, depression, and learning and memory impairment in offspring. However, the underlying molecular biological mechanisms remain unclear. In the current study, offspring CD-1 mice were separated from their mothers from postnatal day 4 to postnatal day 21. At 3 months of age, the male offspring were selected for the evaluation of anxiety- and depression-like behaviors and learning and memory function. Western blotting and RT-PCR were used to examine the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density-95, and synaptophysin. Long-term potentiation (LTP) and long-term depression (LTD) were recorded at Schaffer collateral/CA1 synapses. Furthermore, basal synaptic transmission was evaluated via the recording of the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs). The results showed that adult offspring CD-1 mice displayed anxiety- and depressive-like behaviors as well as impaired spatial learning and memory abilities. Electrophysiological analysis indicated that MS impaired LTP, enhanced LTD, and reduced the frequency of mEPSCs in pyramidal neurons in the CA1 region. Our findings suggested that MS can lead to anxiety, depression, and cognitive deficits, and these effects are associated with alterations in the levels of synaptic plasticity-associated proteins, consequently, also synaptic plasticity.

Naringin alleviates fluoride-induced neurological impairment: A focus on the regulation of energy metabolism mediated by mitochondrial permeability transition pore

The neurological impairment induced by fluoride is associated with mitochondrial dysfunction. Normal mitochondrial permeability transition pore (mPTP) opening plays a pivotal role in mitochondrial function. However, it remains unclear whether p53-dependent mPTP-related mitochondrial apoptosis is associated with fluoride-induced neurological impairment, and the alleviation of naringin on those. In vivo, NaF-treated rats had impaired learning and memory abilities, damaged hippocampal structure, and higher respiratory exchange rates (RER). In vitro, the increased apoptosis rates, excessive opening of mPTP, and decreased mitochondrial membrane potential (MMP) were observed in PC12 cells treated with NaF. The protein expressions of p53, CytoC, and cleaved caspase 3 were significantly increased in hippocampi of rats treated with 50 mg/L and 100 mg/L NaF and in 40 mg/L and 80 mg/L NaF-treated PC12 cells, while the protein expression of CypD remains stable. And the changes of p53 and CypD were also confirmed by the immunofluorescence staining in vivo. After inhibiting the expression of p53 with pifithrin-α and p53-siRNA, the decreased apoptosis rates and mPTP opening, increased MMP, and decreased protein expressions of p53, CytoC, and cleaved caspase 3 were observed in NaF-treated PC12 cells. Rats, treated with NaF and naringin, had alleviated impaired neurological function, and had lower RER than rats treated with NaF alone. And compared with those in the NaF group, the decreased apoptosis rates and mPTP opening, and increased MMP were also found in PC12 cells treated with NaF and naringin. Furthermore, hippocampi of rats and PC12 cells treated with NaF and naringin had decreased protein expressions of p53, CytoC, and cleaved caspase 3. Our results indicate that fluoride activates the p53-dependent mPTP-related mitochondrial apoptosis, which then affects energy metabolism, resulting in neurological impairment. Additionally, naringin can alleviate this damage, and further studies on the potential health benefits of naringin are needed.

Dual-factor model of sleep and diet: a new approach to understanding central fatigue.

Numerous studies have recently examined the impact of dietary factors such as high-fat diets on fatigue. Our study aims to investigate whether high-fat diet (HFD) alone or combined with alternate-day fasting (ADF) can lead to the central fatigue symptoms and to investigate the potential integration of dietary and sleep variables in the development of central fatigue models. Seventy-five male Wistar rats were divided into five groups: control, HFD, HFD + ADF, modified multiple platform method (MMPM), and MMPM+HFD + ADF. Each group underwent a 21-day modeling period according to their respective protocol. Their behavioral characteristics, fatigue biochemical markers, hippocampal pathological changes, mitochondrial ultrastructure, and oxidative stress damage were analyzed. Our findings demonstrate that using only HFD did not cause central fatigue, but combining it with ADF did. This combination led to reduced exercise endurance, decreased locomotor activity, impaired learning and memory abilities, along with alterations in serum levels of alanine aminotransferase (ALT), creatine kinase (CK), and lactate (LAC), as well as hippocampal pathological damage and other central fatigue symptoms. Moreover, the MMPM+HFD + ADF method led to the most obvious central fatigue symptoms in rats, including a variety of behavioral changes, alterations in fatigue-related biochemical metabolic markers, prominent pathological changes in hippocampal tissue, severe damage to the ultrastructure of mitochondria in hippocampal regions, changes in neurotransmitters, and evident oxidative stress damage. Additionally, it was observed that rats subjected to HFD + ADF, MMPM, and MMPM+HFD + ADF modeling method exhibited significant brain oxidative stress damage. We have demonstrated the promotive role of dietary factors in the development of central fatigue and have successfully established a more stable and clinically relevant animal model of central fatigue by integrating dietary and sleep factors.

Ovariectomy exacerbates the disturbance of excitation- inhibition balance in the brain of APP/PS-1/tau mice.

The prevalence of Alzheimer's disease (AD) is significantly gender-differentiated, with the number of female AD patients far exceeding that of males, accounting for two-thirds of the total prevalence. Although postmenopausal AD mice have been shown to have more prominent pathologic features and memory impairments than normal AD mice, the relevant molecular mechanisms leading to these outcomes have not been well elucidated. In the present study, we used the disturbance of excitation-inhibition balance in the postmenopausal brain as an entry point to explore the link between estrogen deficiency, disorders of the glutamatergic-GABAergic nervous system, and memory impairment. Wild-type (WT) mice and APP/PS1/tau (3 × Tg-AD) mice (10 months old) were randomly divided into four groups: WT+Sham group, WT+OVX group, 3 × Tg-AD+Sham group and 3 × Tg-AD+OVX group. Ovariectomy (OVX) was performed in the WT+OVX group and the 3 × Tg-AD+OVX group, and sham surgery was performed in the WT+Sham group and the 3 × Tg-AD+Sham group. The learning and memory ability and the anxiety and depression-like behavior changes of mice were evaluated by behavioral experiments, and the association between estrogen-estrogen receptors pathway and glutamatergic/GABAergic nervous system and female AD was evaluated by neurochemical experiments. In WT and 3 × Tg-AD mice, OVX resulted in impaired learning and memory abilities and anxiety and depression-like behaviors; reduced estrogen levels and downregulated the expression of estrogen receptors; upregulated the expression of amyloid-β, amyloid precursor protein, presenilin 1, and p-tau; upregulated the expression of Bcl-2-associated X protein and downregulated the expression of B-cell lymphoma-2, promoting cell apoptosis; reduced the number of neuronal dendrites and downregulated the expression of postsynaptic density protein-95; more importantly, OVX increased brain glutamate levels but downregulated the expression of N-methyl-D-aspartate receptor-2B, excitatory amino acid transporter 1, excitatory amino acid transporter 2, γ-aminobutyric acid receptor-A and γ-aminobutyric acid receptor-B. Our results suggested that OVX-induced estrogen-estrogen receptors pathway disruption caused learning and memory impairment and anxiety and depression-like behaviors, upregulated the expression of AD pathological markers, promoted apoptosis, destroyed neuronal structure, and most importantly, caused glutamatergic/GABAergic nervous system disorders.

Impaired neurogenesis induced by fluoride via the Notch1 signaling and effects of carvacrol intervention

The negative regulation on neurogenesis has been implicated in fluoride neurotoxicity, while the evidence is limited. To explore whether fluoride interferes with neurogenesis via the Notch1 signaling and the potential alleviation effects of carvacrol (CAR), we conducted in vivo and in vitro experiments, as well as epidemiological analyses in this study. The results showed that urinary fluoride levels and circulating Notch1 levels were associated with IQ levels in boys. NaF-treated rats had fewer neurons, lower densities of dendritic spines, depressed neurogenesis, and impaired learning and memory abilities. In vitro experiments using undifferentiated PC12 cells mimicking neurogenesis revealed that NaF suppressed differentiation and neurite outgrowth. Besides, Notch1 signaling activation was detected in vivo and in vitro. The latter was confirmed using an in vitro model supplemented with DAPT, a potent Notch1 inhibitor. Furthermore, CAR supplementation negatively regulated NICD1 and Hes1 expressions and promoted hippocampal neurogenesis, thereby improving neurological functions in NaF-treated rats. These findings indicated that the inhibition of neurogenesis in hippocampi induced by fluoride via Notch1 signaling activation may be one of the underlying mechanisms of its neurotoxicity, and that CAR significantly alleviated the neurotoxicity of NaF via the Notch1 signaling.

Silencing CD28 attenuated chest blast exposure-induced traumatic brain injury through the PI3K/AKT/NF-κB signaling pathway in male mice

In modern war or daily life, blast-induced traumatic brain injury (bTBI) is a growing health concern. Our previous studies demonstrated that inflammation was one of the main features of bTBI, and CD28-activated T cells play a central role in inflammation. However, the mechanism of CD28 in bTBI remains to be elucidated. In this study, traumatic brain injury model induced by chest blast exposure in male mice was established, and the mechanism of CD28 in bTBI was studied by elisa, immunofluorescence staining, flow cytometry analysis and western blot. After exposure to chest shock wave, the inflammatory factors IL-4, IL-6 and HMGB1 in serum were increased, and CD3+ T cells, CD4+ and CD8+ T cell subsets in the lung were activated. In addition, chest blast exposure resulted in impaired spatial learning and memory ability, disruption of the blood-brain barrier (BBB), and the expression of Tau, p-tau, S100β and choline acetyltransferase were increased. The results indicated that genetic knockdown of CD28 could inhibit inflammatory cell infiltration, as well as the activation of CD3+ T cells, CD4+ and CD8+ T cell subsets in the lung, improve spatial learning and memory ability, and ameliorate BBB disruption and hippocampal neuron damage. Moreover, genetic knockdown of CD28 could reduce the expression of p-PI3K, p-AKT and NF-κB. In conclusion, chest blast exposure could lead to bTBI, and attenuate bTBI via the PI3K/AKT/NF-κB signaling pathway in male mice. This study provides new targets for the prevention and treatment of veterans with bTBI.

The Influence of Maternal Hypoxia and Buspirone during Pregnancy on Cognitive Abilities and a Stress Response in Adult Male Offspring.

Spatial learning, memory, and reactivity of the hypothalamic-pituitary-adrenocortical system (HPA axis) were studied in adult male rats, whose mothers during pregnancy were subjected to acute moderate normobaric hypoxia, or repeated injections of buspirone, an agonist of type 1A serotonergic receptors (5HT1A), or their combination. Prenatal treatment with buspirone in rats with prenatal hypoxia impaired learning ability during the first day of 5-day training. A decrease in the effectiveness of long-term memory in comparison with short-term memory was revealed in two groups of rats: prenatal treatment with buspirone in combination with hypoxia and injection of physiological saline without hypoxia. The effectiveness of long-term memory and the level of corticosterone in response to stress did not differ between the groups, which can indicate adaptation of the 5HT1A receptor and the HPA axis to the prenatal buspirone and normobaric hypoxia during ontogeny.

Huangpu Tongqiao Capsule improves cognitive impairment in rats with Wilson disease by inhibiting endoplasmic reticulum stress-mediated apoptosis pathway

To investigate the neuroprotective effect of Huangpu Tongqiao Capsule (HPTQ) in a rat model of Wilson disease (WD) and explore the underlying mechanisms. SD rat models of WD were established by feeding of coppersupplemented chow diet and drinking water for 12 weeks, and starting from the 9th week, the rats were treated with low-, moderate- and high-dose HPTQ, penicillamine, or normal saline by gavage on a daily basis for 3 weeks. Copper levels in the liver and 24-h urine of the rats were detected, and their learning and memory abilities were evaluated using Morris water maze test. HE staining was used to observe morphological changes of CA1 region neurons in the hippocampus, and neuronal apoptosis was detected with TUNEL staining. Hippocampal expressions of endoplasmic reticulum stress (ERS)-mediated apoptosis pathway-related proteins GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 at both the mRNA and protein levels were detected using RT-qPCR, immunofluorescence assay or Western blotting. Compared with normal control rats, the rat models with copper overload-induced WD exhibited significantly increased copper levels in both the liver and 24-h urine, impaired learning and memory abilities, obvious hippocampal neuronal damage in the CA1 region and increased TUNEL-positive neurons (P<0.01), with also lowered mRNA and protein expressions of GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 in the hippocampus (all P<0.01). Treatments with HPTQ and penicillamine significantly lowered copper level in the liver but increased urinary copper level, improved learning and memory ability, alleviated neuronal damage and apoptosis in the hippocampus, and decreased hippocampal expressions of GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 in the rat models (P<0.01 or 0.05). HPTQ Capsule has neuroprotective effects in rat models of WD possibly by inhibiting ERS-mediated apoptosis pathway.

Remimazolam Attenuates LPS-Derived Cognitive Dysfunction via Subdiaphragmatic Vagus Nerve Target α7nAChR-Mediated Nrf2/HO-1 Signal Pathway.

Sepsis-induced neuroinflammation is significantly associated with sepsis-related brain dysfunction. Remimazolam is a novel ultra-short-acting benzodiazepine anesthetic with multiple organ protective effects. However, it is unknown whether remimazolam can ameliorate LPS-induced brain impairment. In this study, Lipopolysaccharide (5mg/kg, LPS) severely impaired Sprague-Dawley rats spatial learning ability, memory, and cognitive function. However, remimazolam treatment showed a protective effect on LPS-induced cognitive dysfunction. Remimazolam partly reversed LPS-induced splenomegaly, decreased serum cytokine expression, suppressed hippocampal M1 microglial activation, and mitigated oxidative stress injury and neuroinflammation. Electroacupuncture (EA) or PNU282987 treatment improved LPS-induced cognitive dysfunction and also significantly inhibited neuroinflammation and systemic inflammation. However, MLA, ML385, or subdiaphragmatic vagus nerve (SDV) treatment abolished the protective effects of remimazolam. Further mechanistic studies showed that remimazolam induces protective effects by activating subdiaphragmatic vagus nerve target α7nAChR-mediated Nrf2/HO-1 signaling pathway. These results demonstrate that remimazolam can up-regulate α7nAChR, Cyto-Nrf2, HO-1, and cognitive-related (CREB, BDNF, PSD95) protein expressions, suppress M1 microglia, ameliorate neuroinflammation or systemic inflammation, and reverse cognitive dysfunction. Therefore, this study provides insight into a new therapeutic target for the treatment of sepsis-induced cerebral dysfunction.

Synaptic and mitochondrial mechanisms behind alcohol-induced imbalance of excitatory/inhibitory synaptic activity and associated cognitive and behavioral abnormalities.

Alcohol consumption during pregnancy can significantly impact the brain development of the fetus, leading to long-term cognitive and behavioral problems. However, the underlying mechanisms are not well understood. In this study, we investigated the acute and chronic effects of binge-like alcohol exposure during the third trimester equivalent in postnatal day 7 (P7) mice on brain cell viability, synapse activity, cognitive and behavioral performance, and gene expression profiles at P60. Our results showed that alcohol exposure caused neuroapoptosis in P7 mouse brains immediately after a 6-hour exposure. In addition, P60 mice exposed to alcohol during P7 displayed impaired learning and memory abilities and anxiety-like behaviors. Electrophysiological analysis of hippocampal neurons revealed an excitatory/inhibitory imbalance in alcohol-treated P60 mice compared to controls, with decreased excitation and increased inhibition. Furthermore, our bioinformatic analysis of 376 dysregulated genes in P60 mouse brains following alcohol exposure identified 50 synapse-related and 23 mitochondria-related genes. These genes encoded proteins located in various parts of the synapse, synaptic cleft, extra-synaptic space, synaptic membranes, or mitochondria, and were associated with different biological processes and functions, including the regulation of synaptic transmission, transport, synaptic vesicle cycle, metabolism, synaptogenesis, mitochondrial activity, cognition, and behavior. The dysregulated synapse and mitochondrial genes were predicted to interact in overlapping networks. Our findings suggest that altered synaptic activities and signaling networks may contribute to alcohol-induced long-term cognitive and behavioral impairments in mice, providing new insights into the underlying synaptic and mitochondrial molecular mechanisms and potential neuroprotective strategies.

Unraveling the Role of miR-200b-3p in Attention-Deficit/Hyperactivity Disorder (ADHD) and Its Therapeutic Potential in Spontaneously Hypertensive Rats (SHR).

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children with unknown etiology. Impaired learning ability was commonly reported in ADHD patients and has been associated with dopamine uptake in the striatum of an animal model. Another evidence also indicated that micro-RNA (miR)-200b-3p is associated with learning ability in various animal models. However, the association between miR-200b-3p and ADHD-related symptoms remains unclear. Therefore, the current study investigated the role of miR-200b-3p in ADHD-related symptoms such as inattention and striatal inflammatory cytokines. To verify the influence of miR-200b-3p in ADHD-related symptoms, striatal stereotaxic injection of miR-200b-3p antagomir (AT) was performed on spontaneously hypertensive rats (SHR). The antioxidant activity and expressions of miR-200b-3p, slit guidance ligand 2 (Slit2), and inflammatory cytokines in the striatum of SHR were measured using quantitative real-time polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), immunoblotting, and enzyme-linked immunosorbent assay (ELISA). The spontaneous alternation of SHR was tested using a three-arm Y-shaped maze. The administration of miR-200b-3p AT or taurine significantly decreased striatal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in SHR, along with increased super-oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and significantly higher spontaneous alternation. In this paper, we show that miR-200b-3p AT and taurine alleviates ADHD-related symptoms in SHR. These findings provide insights into ADHD's molecular basis and suggest miR-200b-3p as a potential therapeutic target. Concurrently, this study also suggests broad implications for treating neurodevelopmental disorders affecting learning activity such as ADHD.

Levosimendan Ameliorates Hypoxia-Induced Brain Injury in Rats by Modulating PTEN/Akt Signaling Pathway-Mediated Ferroptosis.

Levosimendan (Levo) is a drug commonly used to treat heart failure. Recent studies have suggested that Levo may have neuroprotective effects, but it is still unknown how exactly it contributes to hypoxia-induced brain damage. Thus, the aim of this study was to investigate how Levo affects hypoxia-induced brain damage and to clarify any possible underlying mechanisms. One group of rats (Levo group) was pretreated with Levo via oral force-feeding for four weeks. Another group (Ferrostatin-1 (Fer-1) group) was pretreated with intraperitoneal injections of Fer-1 for four weeks. A rat model of chronic hypoxia was created by treating rats with 13% O2 for 14 days in a closed hypoxia chamber. For each group (Control, Model, Levo, Fer-1), we evaluated learning and memory capacity and the morphology and structure of neurons in the rats' brain tissue. Other measurements included tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6); malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); Fe2+; apoptosis; cleaved caspase-3, caspase-3; phosphatase and tensin homolog (PTEN), protein kinase B (Akt), phosphorylated Akt (p-Akt); and ferroptosis-related proteins Nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11). The Model group rats had considerably fewer neurons than the Control group, with loosely arranged cells, and markedly impaired learning and memory abilities (p < 0.05). Oxidative damage and inflammation in brain tissues of the Model group were significantly intensified, accompanied by a substantial increase in neuronal apoptosis (p < 0.05). PTEN protein, Fe2+ concentration, and cleaved caspase-3 expression were all significantly upregulated, whereas p-Akt, Nrf2, GPX4, and SLC7A11 proteins were dramatically downregulated (p < 0.05). Both the Levo and Fer-1 groups demonstrated significantly more neurons and closely arranged cells than the Model group, along with a notable improvement in learning and memory abilities (p < 0.05). Oxidative damage and inflammation in brain tissues of the Levo and Fer-1 groups were markedly alleviated, and neuronal apoptosis was suppressed (p < 0.05). p-Akt, Nrf2, GPX4, and SLC7A11 proteins were dramatically upregulated, whereas the expression of cleaved caspase-3, PTEN protein, and Fe2+ content was considerably downregulated (p < 0.05). Levo effectively mitigates brain injury in rats with chronic hypoxia, likely by regulating ferroptosis via the PTEN/Akt signaling pathway.

HUBUNGAN INFEKSI SOIL TRANSMITTED HELMINTH (STH) TERHADAP KARAKTERISTIK MASYARAKAT LINGKUNGAN SEKITAR PETERNAKAN DI DAERAH KLUMPANG KAMPUNG KECAMATAN HAMPARAN PERAK

Worm disease is a common people disease commonly encountered in areas, infections can occur simultaneously by several types of worms atonce. For children, the worm disease will have an inmpact for the impaired learning ability, and for adult will decreasing the work productivity. At the North Sumatra, especially Medan City, prevalence of worms in children around (60-70%) of all cases. Research on Soil Transmitted Helminth (STH) Infectious Relationship to Characteristic of Livestock Environment Community in Klumpang Kampung Kecamatan Hampatan Perak, conducted on March-June 2023 at Parasitology Laboratory Poltekkes Medan the department of the medical laboratory technology of Health with using eosin 2% method, with population of 26 samples . The research was analytic observational using cross sectional design. The data obtained were analyzedusing chi-square test at 95% confidence level (?= 0,05). Based on study about Connection Infection Soil Transmitted Helminth (STH) Against Characteristics of Environmental Societies Around Livestock in Klumpang Kampung District Silver Obstacle , obtained results of the 26 samples identified 5 infected samples were found worm Ascaris lumbricoides (20%), with connection STH infection against age 19.2 % only experienced by children just . There's a relationship STH infection against type gender . There's a relationship between education with STH infection . There's a relationship between work with STH infection

Co-exposure to lead, mercury, and cadmium induces neurobehavioral impairments in mice by interfering with dopaminergic and serotonergic neurotransmission in the striatum.

Humans are exposed to lead (Pb), mercury (Hg), and cadmium (Cd) through various routes, including drinking water, and such exposure can lead to a range of toxicological effects. However, few studies have investigated the toxic effects of exposure to mixtures of metals, particularly in relation to neurotoxicity. In this study, 7-week-old male mice were exposed to Pb, Hg, and Cd individually or in combination through their drinking water for 28 days. The mice exposed to the metal mixture exhibited significantly reduced motor coordination and impaired learning and memory abilities compared to the control group and each of the single metal exposure groups, indicating a higher level of neurotoxicity of the metal mixture. The dopamine content in the striatum was significantly lower in the metal mixture exposure group than in the single metal exposure groups and the control group. Furthermore, compared to the control group, the metal mixture exposure group showed a significantly lower expression level of tyrosine hydroxylase (TH) and significantly higher expression levels of dopamine transporter (DAT), tryptophan hydroxylase 1 (TPH1), and serotonin reuptake transporter (SERT). Notably, there were no significant differences in SERT expression between the single metal exposure groups and the control group, but SERT expression was significantly higher in the metal mixture exposure group than in the single metal and control groups. These findings suggest that the key proteins involved in the synthesis and reuptake of dopamine (TH and DAT, respectively), as well as in the synthesis and reuptake of serotonin (TPH1 and SERT, respectively), play crucial roles in the neurotoxic effects associated with exposure to metal mixtures. In conclusion, this study demonstrates that simultaneous exposure to different metals can impact key enzymes involved in dopaminergic and serotonergic neurotransmission processes, leading to disruptions in dopamine and serotonin homeostasis and consequently a range of detrimental neurobehavioral effects.

Transplanting old organs promotes senescence in young recipients

In clinical organ transplantation, donor and recipient ages may differ substantially. Old donor organs accumulate senescent cells that have the capacity to induce senescence in naïve cells. We hypothesized that the engraftment of old organs may induce senescence in younger recipients, promoting age-related pathologies. When performing isogeneic cardiac transplants between age-mismatched C57BL/6 old donor (18 months) mice and young and middle-aged C57BL/6 (3- or 12- month-old) recipients , we observed augmented frequencies of senescent cells in draining lymph nodes, adipose tissue, livers, and hindlimb muscles 30 days after transplantation. These observations went along with compromised physical performance and impaired spatial learning and memory abilities. Systemic levels of the senescence-associated secretory phenotype factors, including mitochondrial DNA (mt-DNA), were elevated in recipients. Of mechanistic relevance, injections of mt-DNA phenocopied effects of age-mismatched organ transplantation on accelerating aging. Single treatment of old donor animals with senolytics prior to transplantation attenuated mt-DNA release and improved physical capacities in young recipients. Collectively, we show that transplanting older organs induces senescence in transplant recipients, resulting in compromised physical and cognitive capacities. Depleting senescent cells with senolytics, in turn, represents a promising approach to improve outcomes of older organs.

The Role of Acetylation and Methylation of Rat Hippocampal Histone H3 in the Mechanism of Aluminum-Induced Neurotoxicity.

Aluminum is a known neurotoxin and a major environmental contributor to neurodegenerative diseases such as Alzheimer's disease (AD). We uesd a subchronic aluminum chloride exposure model in offspring rats by continuously treating them with AlCl3 solution from the date of birth until day 90 in this research. Then evaluated the neurobehavioral changes in rats, observed the ultrastructural changes of hippocampal synapses and neurons, and examined the level of hippocampal acetylated histone H3 (H3ac), the activity and protein expression of hippocampal HAT1 and G9a, and the protein expression level of H3K9 dimethylation (H3K9me2). The findings demonstrated that aluminum-treated offspring rats had impaired learning and memory abilities as well as ultrastructural alterations in hippocampal synapses and neurons. The level of histone H3ac was decreased along with decreased protein expression and activity of HAT1, while level of H3K9me2 was increased along with increased protein expression and activity of G9a.

High-fat diet induces cognitive impairment through repression of SIRT1/AMPK-mediated autophagy

Aims: Recent evidence suggests an association between a high-fat diet (HFD) and cognitive decline. HFD may reduce synaptic plasticity and cause tau hyperphosphorylation, but the mechanisms involved remain unclear. The purpose of this study was to explore whether Sirtuin1 (SIRT1)/AMP-activated protein kinase (AMPK) pathway was involved in this pathogenic effect in the HFD exposed mice.Methods: C57BL/6 mice at 12 months of age were fed a standard (9% kcal fat) or high-fat (60% kcal fat) diet for 22 weeks, and Neuro-2a (N2a) cells were treated with normal culture medium or a palmitic acid (PA) medium (100uM) for 40 h. After that, cognitive function was tested by Morris water maze (MWM). The levels of proteins involved in SIRT1/AMPK pathway and autophagy were measured using western blotting and immunofluorescence. We also assessed the phosphorylation of tau protein and synapse.Results: The mice presented impaired learning and memory abilities. We further found decreased levels of synaptophysin (Syn) and brain-derived neurotrophic factor (BDNF), increased tau46 and phosphorylated tau protein, and damaged neurons in mice after HFD or in N2a cells treated with PA medium. Moreover, HFD can also reduce the expression of SIRT1, inhibit AMPK phosphorylation, and block autophagic flow in both mice and cells. After treating the cells with the SIRT1 agonist SRT1720, SIRT1/AMPK pathway and autophagy-related proteins were partially reversed and the number of PA-induced positive cells was alleviated in senescence-associated β-galactosidase (SA-β-gal) staining.Conclusions: HFD may inhibit the expression of SIRT1/AMPK pathway and disrupt autophagy flux, and result in tau hyperphosphorylation and synaptic dysfunction during aging, which ultimately lead to cognitive decline.

Impaired neural circuitry of hippocampus in Pax2 nervous system-specific knockout mice leads to restricted repetitive behaviors.

Restricted repetitive behaviors (RRBs), which are associated with many different neurological and mental disorders, such as obsessive-compulsive disorder (OCD) and autism, are patterns of behavior with little variation and little obvious function. Paired Box 2 (Pax2) is a transcription factor that is expressed in many systems, including the kidney and the central nervous system. The protein that is encoded by Pax2 has been implicated in the development of the nervous system and neurodevelopmental disorders. In our previous study, Pax2 heterozygous gene knockout mice (Pax2+/- mice) showed abnormally increased self-grooming and impaired learning and memory abilities. However, it remains unclear which cell type is involved in this process. In this study, we deleted Pax2 only in the nervous system to determine the regulatory mechanism of Pax2 in RRBs. In this study, Pax2 nervous system-specific knockout mice (Nestin-Pax2 mice) aged 6-8 weeks and Pax2 flox mice of the same age were recruited as the experimental group. Tamoxifen and vehicle were administered via intraperitoneal injection to induce Pax2 knockout after gene identification. Western blotting was used to detect Pax2 expression. After that, we assessed the general health of these two groups of mice. The self-grooming test, marble burying test and T-maze acquisition and reversal learning test were used to observe the lower-order and higher-order RRBs. The three-chamber test, Y-maze, and elevated plus-maze were used to assess social ability, spatial memory ability, and anxiety. Neural circuitry tracing and transcriptome sequencing (RNA-seq) were used to observe the abnormal neural circuitry, differentially expressed genes (DEGs) and signaling pathways affected by Pax2 gene knockout in the nervous system and the putative molecular mechanism. (1) The Nestin-Pax2 mouse model was successfully constructed, and the Nestin-Pax2 mice showed decreased expression of Pax2. (2) Nestin-Pax2 mice showed increased self-grooming behavior and impaired T-maze reversal behavior compared with Pax2 flox mice. (3) An increased number of projection fibers can be found in the mPFC projecting to the CA1 and BLA, and a reduction in IGFBP2 can be found in the hippocampus of Nestin-Pax2 mice. The results demonstrated that loss of Pax2 in the nervous system leads to restricted repetitive behaviors. The mechanism may be associated with impaired neural circuitry and a reduction in IGFBP2.