Rat Hippocampal Tissue Research Articles

Whole transcriptome sequencing reveals dexmedetomidine-improves postoperative cognitive dysfunction in rats via modulating lncRNA.

The aim of this study was to explore the underlying mechanism and function of dexmedetomidine (Dex)-regulated long non-coding RNAs (lncRNAs) in improving postoperative cognitive dysfunction (POCD) in rats. The established POCD model, Dex treatment model in rats, Morris water maze testing, and HE staining assays were used to evaluate the efficacy of Dex in POCD treatment in rats. Hippocampus samples of rats from the POCD group and the Dex group were used for lncRNA sequencing. The expression of five differentially expressed lncRNAs (DElncRNAs) was verified by quantitative reverse transcription PCR (qRT-PCR). Competing endogenous RNAs (ceRNA) network was constructed using Cytoscape. The concentration of inflammatory cytokines were measured by ELISA. Microglia proliferation and apoptosis were assessed using CCK-8 assay and flow cytometry, respectively. In the Dex group, the escape latency was shorter, neuron cell injury levels were alleviated, and the expression levels of TNF-α and IL-1β were significantly down-regulated compared with the POCD group. A total of 60 DE lncRNAs were identified, including 16 up- and 44 down-regulated lncRNAs in the Dex group. KEGG pathway analysis revealed that DElncRNAs were significantly enriched in cytokine-cytokine receptor interactions, the p53 signaling pathway, and the NF-kappa B signaling pathway. The qRT-PCR results and ceRNA network suggested that the lncRNA LOC102546895 may play a key role in POCD. LOC102546895 inhibited proliferation while promoting apoptosis in microglial cells and promoted the mRNA and protein expression of the target gene Npas4. Our findings showed that Dex alleviated POCD in rats and regulated lncRNAs expression profile in the hippocampus tissues of rats with POCD. In conclusion, our study outcome proposes that Dex-regulated lncRNA LOC102546895 may play a role in rats with POCD through targeting Npas4.

Effect of Endurance Training with Saffron Consumption on PGC1-α Gene Expression in Hippocampus Tissue of Rats with Alzheimer’s Disease

Background: Alzheimer's disease (AD) is a type of cognitive impairment that disrupts the mitochondrial function and metabolism of neurons. Studies have shown that training is a potent factor in enhancing mitochondrial biogenesis and saffron with its antioxidant properties can improve neurodegenerative disorders effectively. Objectives: Accordingly, the aim of this study was to investigate the effect of endurance training (ET) with saffron consumption on peroxisome proliferator-activated receptor-γ coactivator (PGC-1α) gene expression in hippocampal tissue of rats with AD. Methods: In this experimental study, 40 rats with AD (induced by 8 mg/kg trimethyltin (TMT) injection were divided into five groups of eight rats, including (1) AD control, (2) ET, (3) ET with saffron, (4) saffron, and (5) sham. To investigate the effects of AD induction on PGC1-α, eight healthy rats were assigned to the healthy control group. During eight weeks, groups 2 and 3 ran on a treadmill for eight weeks, three sessions per week, for 15 - 30 min at a speed of 15 - 20 m/min per session. Groups 3 and 4 received 25 mg/kg aqueous extract of saffron peritoneally. One-way ANOVA, Tukey’s post hoc, and two-way ANOVA tests were used for data analysis by SPSS software (P ≤ 0.05). Results: Alzheimer’s disease induction significantly reduced PGC1-α gene expression (P = 0.001) while ET significantly reduced PGC1-α gene expression (P = 0.01) in AD rats. Nevertheless, saffron significantly increased PGC1-α gene expression in AD rats (P = 0.001). The interaction of ET and saffron was significant in increasing PGC1-α gene expression in AD rats (P = 0.001). Conclusions: It seems that ET and saffron consumption have interactive effects on the increase of PGC1-α gene expression in the hippocampal tissue of rats with AD.

Practical Performance of Hippocampal Tissue Resection in Rats in Pharmacomolecular Research.

To explain how to resect hippocampal tissue in rats used as live mammalian subjects for the resection of fresh cerebral tissue in laboratories. Adult male Wistar-Albino rats (n=50) were used for this purpose. The average bodyweight of the rats was 316.4 ± 11.71 g, and the average weight of the resected hippocampal tissues was 1.01 ± 0.03 g; however, there were no statistically significant differences between the body weights and the hippocampal tissue weights (p > 0.05). The hippocampal tissues to be used in the study were excised practically by preserving the original anatomical configuration without injury to the tissue. This paper elucidates a simple, step-by-step methodology for performance in the laboratory in order to improve the standardization of hippocampal tissue dissection.

The Effect of Running on Positive and Negative Slopes on Serotonin Levels in the Hippocampus Tissue of Rats with Alzheimer’s Disease

Background: Alzheimer’s disease (AD) is a type of age-related disease that affects hippocampus tissue. The AD is a type of amnesiac disorder with dysfunction of the brain in which the patient’s mental ability is gradually dissipated. Objectives: The aim of the present study was to investigate the effect of running on positive and negative slopes on serotonin in the hippocampus tissue of rats with AD. Methods: In this experimental study, 18 rats were injected with 8 mg/kg trimethyltin chloride (TMT) intra-peritoneally and after being assured of AD, they were divided into three groups of 6 rats, including (1) control, (2) training on positive slope, and (3) training on negative slope. To investigate the effects of AD induction on the serotonin levels, 6 rats were assigned to the healthy control group. Positive training group (at a speed of 16 m/min on positive upward slope) and negative training group (at a speed of 16 m/min on negative downhill slope) ran on the treadmill for eight weeks, five sessions per week and 60 minutes per session. The Shapiro-Wilk, one-way ANOVA with Tukey’s post hoc tests were used to analyze the data (P ≤ 0.05). Results: The induction of AD significantly decreased serotonin gene expression levels (P = 0.04); nevertheless, running on positive (P = 0.01) and negative slopes (P = 0.001) significantly increased serotonin gene expression levels in rats with AD. Conclusions: Running on positive and negative slopes seems to improve serotonin gene expression levels in the hippocampus tissue of rats with AD.

Treadmill exercise improves LPS-induced memory impairments via endocannabinoid receptors and cyclooxygenase enzymes

Endocannabinoid system and cyclooxygenase enzymes are implicated in neuroinflammation-induced cognitive impairment. It is believed that non-pharmacological treatments such as physical exercise affect neural systems that control behavioral responses. This research examined the effects of treadmill aerobic exercise on the expression of cannabinoid receptors and cyclooxygenases against LPS-induced cognitive disorders in the hippocampus tissue of rats. For this purpose, rats received intraperitoneal injection of 0.25 mg/kg LPS or saline for 9 continuous days before exercise training. They again received a single i.p. injection with 0.5 mg/kg LPS or saline on days 20 and 41 after the beginning of exercise. The exercise groups were forced to run on a motorized treadmill 5 days per week for 8 weeks. After the last exercise training session, the water maze test was conducted to measure cognitive function. Finally, the hippocampus tissue samples of rats were removed and used to determine the levels of gene expression using the Real-Time PCR method. Data showed that the LPS-treated rats had longer escape distance and longer escape latency to reach the hidden platform and they spent less time than the other groups in the target quadrant, but exercise training improved them in the LPS + Exe (LPS + exercise) group. Exercise increased the expression of CB1 receptor in the Sal + Exe (saline + exercise) group and reduced the expression of CB2 receptor, COX-2 and mPGES-1 in the LPS + Exe group compared to the Sal + LPS group. The findings indicate that treadmill exercise may be beneficial for improvement of cognitive function by modulating the neuroinflammatory processes.

RyRs mediate lead-induced neurodegenerative disorders through calcium signaling pathways

Heavy metal lead (Pb) is widely distributed in the environment and can induce neurodegeneration. Accumulating evidence has shown that ryanodine receptors (RyRs) play vital roles in neurodegenerative brain. However, whether aberrant RyRs levels contribute to Pb-induced neurodegeneration has largely remained unknown. In the present study, we report the important role of elevated levels of RyRs in Pb-induced neurodegeneration. Pb was found to upregulate the levels of RyRs in the rat hippocampal tissues and rat pheochromocytoma (PC12) cells. Furthermore, exposure to Pb induced neurodegenerative cognitive impairment in rats, depressed the long-term potentiation (LTP) in the rat brain slices, increased the neuronal intracellular free calcium concentration ([Ca2+]i), inhibited the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclic adenosine 3′,5′-monophosphate (cAMP) response element binding protein (CREB) as well as the expression of anti-apoptotic protein B-cell lymphoma 2 (Bcl2), and activated the phosphorylation of extracellular regulated protein kinases (Erk) protein both in vitro and in vivo. In addition, the knockdown of RyR3 in PC12 cells significantly decreased the [Ca2+]i levels, increased the CaMKIIα and CREB phosphorylation, decrease the phosphorylation of Erk, and elongated the cognitive function-related neurite outgrowth after exposure to Pb. Moreover, treatment with a RyRs agonist showed the involvement of RyRs in Pb-induced depression in LTP in the rat brain slices. In summary, we determined that Pb-mediated upregulation of RyRs led to neurodegeneration via high levels of free calcium, depression of the calcium-dependent CaMKIIα/CREB mnemonic signaling pathway, and activation of the calcium-dependent Erk/Bcl2 apoptotic signaling pathway. These findings on the impact of Pb on the levels of RyRs could further improve our understanding of Pb-induced neurotoxicity and provide a promising molecular target to antagonize Pb-induced neurodegenerative diseases.

The Effect of Endurance Training with Crocin Consumption on IGF-1 and Glycogen Expression in Rat Hippocampus Tissue of Trimethyltin-Treated Model of Alzheimer’s Disease

Objectives: Alzheimer’s disease is one of the most common causes of dementia with metabolic disorders in the nervous system. Nutrition and physical activity are two main factors in the management of this disease. The aim of the present study was to investigate the effect of endurance training with crocin consumption on IGF-1 and glycogen expression in rat hippocampus tissue of a trimethyltin-treated model of Alzheimer’s disease. Methods: In this experimental study, 30 male rats were selected and divided into 5 groups of 6 rats including (1) healthy control, (2) Alzheimer’s control, (3) endurance training, (4) crocin and (5) endurance training with crocin. At first, rats in groups 2 - 5 were induced Alzheimer’s disease by intraperitoneal injection of 8 mg/kg of trimethyltin. Then, during 8 weeks, rats in groups 3, 5, ran on treadmill for 3 sessions per week, each session 15 - 30 minutes at speeds of 15 - 20 m/min and groups 4 and 5 received 25 mg/kg of crocin daily. The results were analyzed by Shapiro-Wilk test and one-way ANOVA with Tukey post hoc (P ≤ 0.05). Results: Alzheimer’s induction with trimethyltin had a significant effect on reduction of IGF-1 gene expression (P = 0.001) and glycogen (P = 0.001); endurance training had a significant effect on increase of IGF-1 (P = 0.001) and glycogen (P = 0.001); crocin consumption had no significant effect on IGF-1 (P = 0.48) and glycogen (P = 0.39); endurance training with crocin consumption had significant effect on increase of IGF-1 (P = 0.001) and glycogen (P = 0.02) as well as endurance training (P = 0.001) and endurance training with crocin consumption rather than crocin consumption had significant effect on increase of IGF-1. Conclusions: Although endurance training results in a significant increase in IGF-1 and glycogen in the hippocampus tissue of Alzheimer’s rats, nonetheless, the use of crocin in combination with endurance training rather than crocin consumption alone can have a greater effect on increased IGF-1 content of the hippocampus in rats with Alzheimer’s.

Polymerization retardation isothermal amplification (PRIA): a strategy enables sensitively quantify genome-wide 5-methylcytosine oxides rapidly on handy instruments with nanoscale sample input.

The current methods for quantifying genome-wide 5-methylcytosine (5mC) oxides are still scarce, mostly restricted with two limitations: assay sensitivity is seriously compromised with cost, assay time and sample input; epigenetic information is irreproducible during polymerase chain reaction (PCR) amplification without bisulfite pretreatment. Here, we propose a novel Polymerization Retardation Isothermal Amplification (PRIA) strategy to directly amplify the minute differences between epigenetic bases and others by arranging DNA polymerase to repetitively pass large electron-withdrawing groups tagged 5mC-oxides. We demonstrate that low abundant 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxycytosine (5caC) in genomic DNA can be accurately quantified within 10 h with 100 ng sample input on a laboratory real-time quantitative PCR instrument, and even multiple samples can be analyzed simultaneously in microplates. The global levels of 5hmC and 5fC in mouse and human brain tissues, rat hippocampal neuronal tissue, mouse kidney tissue and mouse embryonic stem cells were quantified and the observations not only confirm the widespread presence of 5hmC and 5fC but also indicate their significant variation in different tissues and cells. The strategy is easily performed in almost all research and medical laboratories, and would provide the potential capability to other candidate modifications in nucleotides.

P19 Repetitive magnetic stimulation of mouse and rat hippocampal tissue cultures reveals distinct stimulation intensity thresholds for the induction of excitatory synaptic plasticity

P19 Repetitive magnetic stimulation of mouse and rat hippocampal tissue cultures reveals distinct stimulation intensity thresholds for the induction of excitatory synaptic plasticity

LncRNA MALAT1 is involved in sevoflurane-induced neurotoxicity in developing rats.

The purpose of this study is to uncover the effects of long chain noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on sevoflurane-induced neurotoxicity in developing rats. Sevoflurane neurotoxicity model was established by sevoflurane treatment in 7-day-old Sprague-Dawley rats. The rats were treated with Sevo or MALAT1 small interfering RNA to detect the MALAT1 expression, pathological change, ultrastructure, neuronal apoptosis, expression of apoptosis-related proteins, expression of neurotrophic factors BDNF and NGF, spatial learning and memory function change, as well as neuron cell density of hippocampal tissues. MALAT1 was highly expressed in hippocampus tissues of rats. Downregulation of MALAT1 alleviated the pathological change, improved the ultrastructure, inhibited apoptosis of neuronal cells, declined caspase 3 and Bax while elevated Bcl-2, BDNF and NGF, improved capability of spatial learning and memory, and increased density of hippocampal neurons in hippocampal tissues of sevoflurane-induced rats. Suppression of MALAT1 can reduce the apoptosis of hippocampal neurons induced by sevoflurane anesthesia, improve the capability of spatial learning, and memory function and alleviate the loss of hippocampal nerve cells in developing rats. To a certain extent, it plays the role of protecting brain nerve cells.

Inhibition of microRNA-103a inhibits the activation of astrocytes in hippocampus tissues and improves the pathological injury of neurons of epilepsy rats by regulating BDNF

BackgroundThe aim of this study is to explore the effect of microRNA-103a (miR-103a) on astrocytes activation and hippocampal neuron injury in epilepsy rats by targeting brain-derived neurotrophic factor (BDNF).MethodsThe epilepsy rat model was induced by intraperitoneal injection of lithium chloride-pilocarpine. Successful modeled rats were intralateroventricularly microinjected with miR-103a inhibitors, inhibitors negative control (NC), siRNA-NC and BDNF-siRNA, respectively. The RT-qPCR and western blot analysis were used to detect the expression of miR-103a, BDNF and glial fibrillary acidic protein (GFAP) in hippocampus tissues of rats. TUNEL staining was used to detect the apoptosis of hippocampal neurons. The RT-PCR and ELISA was used to detect the levels of TNF-α and IL-6 in hippocampal tissues and in serum, respectively.ResultsIncreased expression of miR-103a, GFAP, and number of apoptotic neurons, decreased expression of BDNF and number of surviving neurons were found in hippocampus tissues of epilepsy rats. After miR-103a inhibitors interfered with epilepsy rats, there showed decreased expression of miR-103a and GFAP, increased expression of BDNF and decreased number of apoptotic neuron as well as increased number of surviving neurons. Compared with miR-103a inhibitors alone, epilepsy rats treated with BDNF-siRNA combined with miR-103a inhibitors significantly increased expression of GFAP in hippocampal tissues of epilepsy rats, increased number of apoptotic neurons and significantly decreased the number of surviving neurons.ConclusionOur study provides evidence that the inhibition of miR-103a can inhibit the activation of astrocytes in hippocampus tissues and improve the pathological injury of neurons of epilepsy rats by regulating BDNF gene.

Effects of Sleep Deprivation (SD) on Rats via ERK1/2 Signaling Pathway

BackgroundSleep deprivation (SD) is common in humans, and sleep loss has a significant influence on health and produces related diseases. Orexin-A has been demonstrated to play a role in physiological processes, including feeding, sleep/wake cycle, and energy metabolism. The aim of this study was to investigate the effect of SD on rats and to define the underlying mechanism.Material/MethodsWe constructed an SD rat model. The Morris water maze test was used to assess rat learning and memory. Imaging of hippocampus and hippocampal tissue in rats were captured by magnetic resonance imaging or electron microscopy. We used the CCK-8 kit to assess cell viability. The level of protein was measured using Western blot analysis, and qRT-PCR was used to evaluate mRNA level.ResultsSD rats had poorer learning and memory and had damage to the hippocampus. SD resulted in shrinkage of hippocampal volume and encephalocele size. SD increased the expression of Orexin-A, OX1R, OX2R, and PARP-1, and decreased the expression of ERK1/2 and p-ERK1/2. Orexin-A (0–10 μM) improved neuron viability, whereas orexin-A (10–100 μM) attenuated neuron viability. SB334867 treatment reduced the viability of neurons treated with orexin-A. NU1025 treatment increased cell viability, especially in neurons treated with orexin-A. SB334867 treatment decreased the p-ERK1/2 levels in neurons treated with orexin-A. NU1025 increased the expression of p-ERK1/2 in neurons treated with orexin-A.ConclusionsSD decreases learning and memory through damage to the hippocampus. Higher concentrations of orexin-A had a major negative effect on hippocampal neurons via OX1R and PARP-1 through inhibition of the ERK1/2 signaling pathway.

High intensity interval training decreases the expressions of KIF5B and Dynein in Hippocampus of Wistar male rats

Although exercise training (ET) with low to moderate intensity improves several physiological aspects of brain, the effects of high intensity interval training (HIIT) are less clear on brain plasticity and cytoplasmic transport. The present study examined the effects of HIIT on the gene and protein expressions of kinesin family member 5B (KIF5B) and Dynein in the Wistar male rat hippocampal tissue. Fourteen male Wistar rats were separated into 2 groups: (1) the training group (TG: n = 7) and (2) the control group (CG: n = 7). The exercise protocol was carried out on a rodent treadmill (5 days a week for 6 weeks). The protein contents of KIF5B and Dynein were determined by the immunohistochemical analysis. Moreover, the Real-Time polymerase chain reaction (Real-Time PCR) procedure was done to measure the KIF5B mRNA and Dynein mRNA expressions. It was observed that HIIT resulted in a significant decrease in the gene expressions of KIF5B and Dynein (P = 0.001), and also the results showed that HIIT leads to a significant decrease in KIF5B (P = 0.001) and Dynein (P = 0.02) protein content of the hippocampal tissue in comparison with sedentary rats. Our findings demonstrated that HIIT is associated with the down-regulation of gene and protein levels of KIF5B and Dynein in the rat hippocampal tissue, although the underlying mechanisms have remained unknown. These changes suggest that HIIT may have negative effects on both the anterograde and retrograde cytoplasmic transports because the cytoplasmic transport is mediated by KIF5B and Dynein.

Difference between natural and artificial sweeteners: Histopathological studies on male albino rat’s brain (hippocampus)

The present work is a trial to compare effect of short and long term administrations of sucrose as a natural widely used sweetener, aspartame as a synthetic non-caloric sweetener and stevia as a novel natural non-caloric sweetener on rats' brain hippocampus. This was achieved using 64 male albino rats. Rats were divided into four groups. The first group served as control group receiving distilled water. The second group represented the sucrose group receiving 10% sucrose solution (weight /volume). The third group served as aspartame group receiving aspartame (75 mg/kg body weight /day).The fourth group represented the stevia group and received (40 mg/kg body weight/day).Animals received different experimental treatments by oral gavage and they were dissected after a short duration of 30 days and long experimental duration of 90 days. Histological investigation of hippocampal sections of hippocampus revealed neuronal degeneration with pyknotic nuclei, dilatation and congestion in blood vessels and spongiform changes in the neuropil after both sucrose and aspartame treatments. On the other hand, stevia treatment to rats showed near to normal pattern of the granular and the neuropil. Histochemical, stained sections of Bromophenol blue stain to hippocampal tissue recorded significant decrease in protein content in hippocampus in sucrose group and aspartame groups respectively after 90 days compared with stevia and control rats. Staining hippocampus tissue of rats treated with sucrose or aspartame with Congo red stain revealed cellular homogenous pink deposits of amyloid throughout the hippocampus tissue. This was decreased and observed as limited or few amyloid depositions in stevia group compared to controls. In conclusion, Stevia, a non-calorific sweetener, is a better alternative to the synthetic sweetener aspartame because stevia has the potential to assist individuals in regulating their weights without any recognized side effects on hippocampus tissue besides its health benefits as a natural antioxidant.

Diosmetin Suppresses Neuronal Apoptosis and Inflammation by Modulating the Phosphoinositide 3-Kinase (PI3K)/AKT/Nuclear Factor-κB (NF-κB) Signaling Pathway in a Rat Model of Pneumococcal Meningitis.

Bacterial meningitis has a high mortality rate and can be challenging to diagnose and manage. This study aimed to evaluate the effect of diosmetin in a rat model of Streptococcus pneumoniae meningitis and to investigate the mechanism of action.Forty rats included a treatment group (n=30) that underwent intracisternal injection with S. pneumoniae, and a sham group (n=10) that underwent intracisternal injection with normal saline. In the treatment group, four days before the inoculation of the bacteria, rats were pre-treated with oral diosmetin 100 mg/kg (n=10) and 200 mg/kg (n=10), and the negative control was pre-treated with normal saline (n=10). Bacterial meningitis was confirmed one day after inoculation by cerebrospinal fluid (CSF) bacterial titer and neurological score. In rat brain tissue, levels of inflammatory mediators were determined by enzyme-linked immunosorbent assay (ELISA) and western blot for protein kinase B (Akt), phosphoinositide 3-kinase (PI3K), myeloid differentiation primary response 88 (MyD88), and nuclear factor-κB (NF-κB), and the TUNEL assay for apoptosis was performed.In the diosmetin-treated group compared with negative control group, the CSF bacterial titer and the level of pro-inflammatory mediators, and the neurological score, were significantly reduced (p<0.01). In the rat hippocampal tissue, levels of Akt, PI3K, MyD88 and NF-κB, and the number of TUNEL-positive apoptotic cells were significantly reduced in the diosmetin-treated group compared with negative control group (p<0.01).In a rat model of bacterial meningitis due to S. pneumoniae, diosmetin reduced neuroinflammation, and neuronal apoptosis by modulating the PI3K/AKT/NF-κB signaling pathway.

Anticonvulsant and Neuroprotective Effects of Dexmedetomidine on Pilocarpine-Induced Status Epilepticus in Rats Using a Metabolomics Approach.

BackgroundStatus epilepticus (SE) is the most extreme form of seizure. It is a medical and neurological emergency that requires prompt and appropriate treatment and early neuroprotection. Dexmedetomidine (DEX) is mainly used for its sedative, analgesic, anxiolytic, and neuroprotective effects with light respiratory depression. The purpose of this study was to comprehensively analyze the metabolic events associated with anticonvulsion and neuroprotection of DEX on pilocarpine-induced status epilepticus rats by LC-MS/MS-based on metabolomics methods combined with histopathology.Material/MethodsIn this research, rats were divided into 3 groups: a normal group, an SE group, and an SE+DEX group. Hippocampus of rats from each group were collected for further LC-MS/MS-based metabolomic analysis. We collected brains for HE staining and Nissl staining. Multivariate analysis and KEGG enrichment analysis were performed.ResultsResults of metabolic profiles of the hippocampus tissues of rats proved that dexmedetomidine relieved rats suffering from the status epilepticus by restoring the damaged neuromodulatory metabolism and neurotransmitters, reducing the disturbance in energy, improving oxidative stress, and alleviating nucleic acid metabolism and amino acid in pilocarpine-induced status epilepticus rats.ConclusionsThis integral metabolomics research provides an extremely effective method to access the therapeutic effects of DEX. This research will further development of new treats for status epilepticus and provide new insights into the anticonvulsive and neuroprotective effects of DEX on status epilepticus.

Silencing lncRNA PVT1 inhibits activation of astrocytes and increases BDNF expression in hippocampus tissues of rats with epilepsy by downregulating the Wnt signaling pathway.

The aim of this study is to investigate the effects of long-chain noncoding RNA plasmacytoma variant translocation 1 (PVT1) on the activation of astrocytes and the expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissues of epileptic rats. The epilepsy rat model was induced by intraperitoneal injection of lithium chloride-pilocarpine. Successfully modeled rats were grouped, and their spatial learning and memory, neuronal loss, number of TdT-mediated dUTP nick labeling (TUNEL)-positive cells, and the expression of cleaved-caspase-3, pro-caspase-3, Bax, Bcl-2, GFAP, BDNF, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, axin, and cyclin D1 in hippocampus tissues were evaluated. Increased expression of PVT1 was found in hippocampus tissues of epileptic rats. Silencing of PVT1 improved spatial learning and memory, decreased neuronal loss, decreased the number of TUNEL-positive cell, decreased the expression of cleaved-caspase-3 and Bax while increased pro-caspase-3 and Bcl-2 expression, decreased the expression of GFAP, increased the expression of BDNF, decreased the expression of TNF-α, IL-1β, and IL-6, and decreased the expression of axin and cyclin D1 in hippocampus tissues in epileptic rats. Our study provides evidence that the inhibition of PVT1 may decrease the loss of neurons, inhibit the activation of astrocytes, and increase the expression of BDNF in hippocampus by downregulating the Wnt signaling pathway.

Transit phases of β-amyloid and tau proteins formation and re-solubilisation in AD rat hippocampus tissue as probed by ATR-IR spectroscopy

ObjectivesAlzheimer's disease (AD) was believed to be mainly due to the accumulation of free radicals that trigger the membrane peroxidation and protein oxidation in brain tissue. The mechanism of β-amyloid (Aβ) formation, aggregation in AlCl3 induced AD in hippocampus rat brain tissue, the curative and the protective effects of Lepedium sativum (LS) water extract as a natural anti-inflammatory, antioxidant and as acetylcholinesterase inhibitor were explored. Materials and methodsAdult Albino male Wistar rats rat divided into; control, AD, curative, protective, and LS groups (n = 20). Hippocampus tissue were studied histologically and spectroscopically by ATR-IR. ResultsMany significant changes in band position, area and half band width of the resultant decomposed bands between AD and the other tested groups. The α-helix band in the raw spectra was resolved into two distinct sub-bands around 1651 and 1659 cm−1 with different percentage areas in all tested groups and in the random coil sub-band as well. A hypothesis on how Aβ is formed and re-solubilized through transit α-helix and random coil formation was postulated in response to LS treatment. In AD rat hippocampus tissue, a significant marked degenerative change was observed in the hippocampal neurons. Most cells appeared smaller, shrunk, deformed and pyknotic nuclei that stained deeply by Congo red. In curative group, the amount of degenerated cells markedly decrease compared to AD group. The intensity of Congo red stained cells was decreased. ConclusionThis study gave a highlight on the therapeutic effect of LS that can manage Aβ formation and re-solubilisation on AD rat model.

Tropomodulin Isoform-Specific Regulation of Dendrite Development and Synapse Formation.

Neurons of the CNS elaborate highly branched dendritic arbors that host numerous dendritic spines, which serve as the postsynaptic platform for most excitatory synapses. The actin cytoskeleton plays an important role in dendrite development and spine formation, but the underlying mechanisms remain incompletely understood. Tropomodulins (Tmods) are a family of actin-binding proteins that cap the slow-growing (pointed) end of actin filaments, thereby regulating the stability, length, and architecture of complex actin networks in diverse cell types. Three members of the Tmod family, Tmod1, Tmod2, and Tmod3 are expressed in the vertebrate CNS, but their function in neuronal development is largely unknown. In this study, we present evidence that Tmod1 and Tmod2 exhibit distinct roles in regulating spine development and dendritic arborization, respectively. Using rat hippocampal tissues from both sexes, we find that Tmod1 and Tmod2 are expressed with distinct developmental profiles: Tmod2 is expressed early during hippocampal development, whereas Tmod1 expression coincides with synaptogenesis. We then show that knockdown of Tmod2, but not Tmod1, severely impairs dendritic branching. Both Tmod1 and Tmod2 are localized to a distinct subspine region where they regulate local F-actin stability. However, the knockdown of Tmod1, but not Tmod2, disrupts spine morphogenesis and impairs synapse formation. Collectively, these findings demonstrate that regulation of the actin cytoskeleton by different members of the Tmod family plays an important role in distinct aspects of dendrite and spine development.SIGNIFICANCE STATEMENT The Tropomodulin family of molecules is best known for controlling the length and stability of actin myofilaments in skeletal muscles. While several Tropomodulin members are expressed in the brain, fundamental knowledge about their role in neuronal function is limited. In this study, we show the unique expression profile and subcellular distribution of Tmod1 and Tmod2 in hippocampal neurons. While both Tmod1 and Tmod2 regulate F-actin stability, we find that they exhibit isoform-specific roles in dendrite development and synapse formation: Tmod2 regulates dendritic arborization, whereas Tmod1 is required for spine development and synapse formation. These findings provide novel insight into the actin regulatory mechanisms underlying neuronal development, thereby shedding light on potential pathways disrupted in a number of neurological disorders.

Mitochondrial damage in hippocampal neurons of rats with epileptic protein expression of Fas and caspase-3.

Epilepsy model in rats was established to observe the behavior and pathological changes, and to detect mitochondrial dysfunction, exploring its possible molecular mechanisms. The epileptic status of Sprague-Dawley (SD) rats was induced by intraperitoneal injection of lithium chloride, and the change of behavior was recorded. Electroencephalogram (EEG) was used to measure the abnormal discharge of neurons in rats. The brain tissue was fixed with polyformaldehyde and the paraffin sections were prepared, and the damage of the hippocampal neurons was observed with Nissl staining. Mitochondrial ATP and mitochondrial DNA were examined to assess mitochondrial dysfunction. Finally, qPCR and western blot analysis were used to detect mRNA and protein expression of fatty acid synthetase (Fas), Fas ligand (FasL) and caspase-3 in rat hippocampal neurons. The correlation between the mitochondrial dysfunction of rat hippocampal neurons and Fas and caspase-3 was analyzed. Compared with the normal group rats, the model group showed typical seizures, which were determined by the Racine attack score. EEG of the hippocampus of the model group was recorded in cluster in model group rats. Nissl staining showed a different degree of damage to the hippocampal neurons in the model group compared with normal rats. The mitochondrial ATP content and DNA content of rat hippocampal neurons in the model group were significantly lower than that of normal rats (P<0.01). The qPCR and western blot results showed that the mRNA and protein expression levels of Fas, FasL and caspase-3 were significantly increased in the hippocampus of rat model group (P<0.01). The expression level of Fas and caspase-3 in hippocampal tissues of rats was negatively correlated with mitochondrial DNA content. In conclusion, seizures cause damage of neuron mitochondria in rat hippocampus leading to death of hippocampal neurons, the mitochondrial damage of hippocampal neurons in epileptic rats was closely related to the expression of Fas and caspase-3.