Treadmill exercise ameliorates chemotherapy-induced memory impairment through Wnt/ß-catenin signaling pathway.

Doxorubicin (DOX) is a widely used chemotherapy drug for various cancers and it is known to induce cognitive impairment. The aim of this study was to investigate the effect of treadmill exercise on chemotherapy-induced memory impairment. We assessed whether DOX affects inflammation, mitochondrial Ca2+ retention capacity, and Wnt/ß-catenin signaling. Male Sprague-Dawley rats were divided into control group, exercise group, DOX-injection group, and DOX-injection and exercise group. To create a DOX-induced memory impairment model, animals were injected intraperitoneally with DOX (2 mg/kg) dissolved in saline solution once a week for 4 weeks. Treadmill exercise was performed once a day, 5 days a week, for 8 consecutive weeks. Short-term memory was determined using the step-down avoidance test. Western blot was performed for the proinflammatory cytokines, Wnt/ß-catenin signaling, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) in the hippocampus. Mitochondrial Ca2+ retention capacity in the hippocampus was also measured. DOX-injection rats showed deterioration of short-term memory along with decreased expression of BDNF and TrkB in the hippocampus. Levels of the proinflammatory cytokines, tumor necrosis factor-α and interleukin-6, were increased in the DOX-injection rats. Wnt/ß-catenin signaling was activated and mitochondrial Ca2+ retention capacity was decreased in the DOX-injection rats. However, treadmill exercise alleviated short-term memory impairment, decreased proinflammatory cytokines, increased BDNF and TrkB expression, and enhanced mitochondrial Ca2+ retention capacity. Treadmill exercise restorated Wnt/ß-catenin signaling pathway. This study demonstrated that treadmill exercise can be used for patients undergoing chemotherapy with DOX.

The effects of exercise and diet on mental status, insulin signaling pathway, and microbiome in obese mice.

The aim of this study was to investigate the effects of exercise and diet on mental status, insulin signaling pathway, serotonin synthesis, and microbiome in high-fat-induced obesity mice. Before the start of this experiment, obesity groups made obese mice by administering a high-fat diet containing 60% fat for 12 weeks. In the obesity with exercise group, after a high-fat diet for 12 weeks, exercise was performed with high-fat diet for 8 weeks. In the obesity with diet group, a high-fat diet for 12 weeks followed by a normal diet for 8 weeks. Depression and anxiety were determined by open field test and elevated plus maze test. Immunohistochemistry for tryptophan hydroxylase (TPH) in the dorsal raphe, western blot analysis for phosphorylated protein kinase B (p-ATK), total AKT (t-AKT), phosphorylated phosphoinositide 3-kinase (p-PI3K), and total PI3K (t-PI3K) in the hippocampus were performed. Analysis of microbiome was also conducted. Obesity-induced depression and anxiety status, suppressed ratio of p-AKT/t-AKT and p-PI3K/t-PI3K, and inhibited TPH synthesis. Exercise and diet improved depression and anxiety status, activated p-AKT/t-AKT and p-PI3K/t-PI3K, and increased TPH synthesis. Exercise and diet improved depression and anxiety status by increasing the insulin signaling pathway and promoting serotonin production. These effects of exercise and diet were almost similar. In addition, exercise and diet regulated the composition of gut microbiota.

Pep-1 Peptide-modified liposomal carriers for intracellular delivery of gold nanoparticles.

A Pep-1 peptide-modified liposomal (Pep1-Lipo) carrier system was investigated to increase the intracellular delivery of gold nanoparticles (Au NPs). Au NPs with a mean diameter of 13 nm were successfully encapsulated into the inner aqueous compartment of the novel carrier using an ethanol injection technique, reserving the distinctive optical characteristics of the surface plasmon resonance peak around 530 nm. The Au NP-loaded liposomal carrier was physically characterized as 150-170 nm in size and 45 mV in zeta potential. Dark field microscopic observation demonstrated that in vitro cellular association and/or translocation of the nanoprobes into the cells was increased by Pep1-Lipo carriers compared to bare Au NPs. In conclusion, this novel liposomal formulation is a promising platform for the intracellular delivery of metallic nanoprobes including Au NPs.

Study on the pathogenesis of liver injury caused by alcohol and drugs.

In the present study, alcohol, lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were administered to experimental mice. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 concentrations, and collagen type 1alpha (COL-1A) and fibronectin expressions were measured to evaluate pathophysiology of liver injury. Levels of ALT and AST were significantly increased by alcohol treatment. Alcohol with LPS treatment increased ALT and AST levels more than alcohol alone treatment, but it was not statistically significant. Alcohol with CCL4 treatment significantly increased ALT and AST levels more than alcohol alone treatment. Alcohol with LPS and CCL4 treatment significantly increased ALT and AST levels more than alcohol with CCL4 treatment. Concentrations of TNF-α, IL-1ß, and IL-6 were significantly enhanced by alcohol treatment. Alcohol with LPS treatment significantly enhanced concentrations of TNF-α, IL-1ß, and IL-6 more than alcohol alone treatment. Alcohol with CCL4 treatment significantly enhanced TNF-α, IL-1ß, and IL-6 concentrations more than alcohol alone treatment. Alcohol with LPS and CCL4 treatment increased TNF-α, IL-1ß, and IL-6 concentrations more than alcohol with CCL4 treatment, but it was not statistically significant. COL-1A and fibronectin expressions were significantly increased by alcohol treatment. Alcohol with LPS treatment significantly increased COL-1A and fibronectin expressions more than alcohol alone treatment. Alcohol with CCL4 treatment significantly increased COL-1A and fibronectin expressions more than alcohol alone treatment. Alcohol with LPS and CCL4 treatment increased COL-1A and fibronectin expressions more than alcohol with CCL4 treatment, but it was not statistically significant.

Treadmill exercise in obese maternal rats during pregnancy improves spatial memory through activation of phosphatidylinositol 3-kinase pathway in the hippocampus of rat pups.

Maternal nutrition is necessary for the growth of the fetus, and excessive intake of nutrients interferes with brain development in offspring. In the current study, the effect of treadmill running during pregnancy in obese maternal rats on spatial learning memory and spatial working memory in rat pups was investigated. Phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and extracellular signal-regulated kinase 1 and 2 (ERK1/2) was also identified in rat pups. Female rats were divided into the normal diet group and the high-fat diet group for 7 weeks, including pregnancy and lactation. Maternal treadmill running was performed for 4 weeks. The born rat pups were classified into a control group, a treadmill exercise group, a high-fat diet group, a high-fat diet and treadmill exercise group according to the status of maternal rats. Radial 8-arm maze task for spatial learning memory and Morris water maze task for spatial working memory were done. Western blot analysis was conducted to determine the expressions of PI3K, Akt, ERK1/2. In the current results, maternal treadmill running during pregnancy improved spatial learning memory and spatial working memory in rat pups born to obese maternal rats. This improving effect of memory was due to the enhanced phosphorylation of PI3K, Akt, and ERK1/2 by treadmill running.

Tadalafil improves short-term memory by suppressing ischemia-induced apoptosis of hippocampal neuronal cells in gerbils.

Cerebral ischemia resulting from transient or permanent cerebral artery occlusion leads to neuronal cell death, and eventually causes neurological impairments. Tadalafil (Cialis)is a long-acting phosphodiesterase type-5 (PDE-5) inhibitor used to treat erectile dysfunction. The therapeutic effects of PDE-5 inhibitors on chronic obstructive pulmonary disease, prostate hyperplasia, hypertension, and coronary heart disease have been reported. The present study investigated the effects of tadalafil on short-term memory, cyclic guanosine monophosphate (cGMP) level, apoptotic neuronal cell death, and cell proliferation in the hippocampus following transient global ischemia in gerbils. For this study, a step-down avoidance task, cGMP assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, and immunohistochemistry for caspase-3 and 5-bromo-2'-deoxyuridine were performed. The results revealed that ischemic injury increased apoptotic neuronal cell death in the hippocampal CA1 region, impaired short-term memory, and decreased cGMP level. Ischemic injury enhanced cell proliferation in the hippocampal dentate gyrus. Tadalafil treatment improved short-term memory by suppressing ischemia-induced apoptotic neuronal cell death in the hippocampal CA1 region, and decreased cGMP level. Also, tadalafil suppressed the ischemia-induced increase in cell proliferation in the hippocampal dentate gyrus. We showed that tadalafil can overcome ischemia-induced apoptotic neuronal cell death, thus facilitates recovery following ischemic cerebral injury.

Vardenafil increases cell proliferation in the dentate gyrus through enhancement of serotonin expression in the rat dorsal raphe.

This study was conducted to evaluate the effects of vardenafil (Levitra), a phosphodiesterase-5 (PDE-5) inhibitor, on cell proliferation in the hippocampal dentate gyrus and on 5-hyroxytryptamine (5-HT, serotonin) synthesis and tryptophan hydroxylase (TPH) expression in the rat dorsal raphe nucleus. Male Sprague-Dawley rats were divided into 6 groups (n=5 in each group): a control group, a 0.5 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-1 day vardenafil-treated group, a 2 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-3 day vardenafil-treated group, and a 1 mg/kg-7 day vardenafil-treated group. 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry was then performed to evaluate cell proliferation in the dentate gyrus. In addition, 5-HT and TPH immunohistochemistry was conducted to evaluate serotonin expression in the dorsal raphe. The results revealed that treatment with vardenafil increased cell proliferation in the dentate gyrus and enhanced 5-HT synthesis and TPH expression in the dorsal raphe in a dose- and duration-dependent manner. The findings demonstrate that the increasing effect of vardenafil on cell proliferation is closely associated with the enhancing effect of vardenafil on serotonin expression under normal conditions.

Effects of sildenafil citrate on peripheral fatigue and exercise performance after exhaustive swimming exercise in rats.

Sildenafil citrate is a potent and selective inhibitor of phosphodiesterase type-5 used to treat erectile dysfunction. We investigated the effects of sildenafil citrate treatment on peripheral fatigue and exercise performance after exhaustive swimming exercise in rats. The rats in the sildenafil citrate-treated groups received sildenafil citrate orally once a day for 14 consecutive days at respective dosage. On the 14 days after starting experiment, each animal was submitted to swimming test with intensity equivalent to overload. The exhaustion was defined as a state in which coordinated movements did not return to the water surface for breathing within 10 sec. Western blot for monocarboxylate transporter (MCT)1, MCT4, and neuronal nitric oxide synthase (nNOS) were performed. Exhaustive swimming exercise decreased time of exhaustion and increased lactate concentration, however, sildenafil citrate enhanced time of exhaustion and decreased lactate concentration. Exhaustive swimming exercise increased MCT1 and MCT4 expressions in the gastrocnemius muscles and sildenafil citrate further enhanced MCT1 and MCT4 expressions in the exhaustive swimming exercise rats. Exhaustive swimming exercise decreased nNOS expression in the gastrocnemius muscles and sildenafil citrate enhanced nNOS expression in the exhaustive swimming exercise rats. The most potent effect appeared in the 20-mg/kg sildenafil citrate. Sildenafil citrate might be proposed as a potential ergogenic aid through antiperipheral fatigue.

Effect of sildenafil citrate on brain central fatigue after exhaustive swimming exercise in rats.

Sildenafil citrate, a potent and selective inhibitor of phosphodiesterase type-5, is used clinically to treat erectile dysfunction and pulmonary arterial hypertension. We investigated the effect of sildenafil citrate on brain central fatigue through serotonin (5-hydroxytryptamine, 5-HT) synthesis after exhaustive swimming exercise in rats. The rats in the sildenafil citrate-treated groups received sildenafil citrate orally once a day for 14 consecutive days at respective dosage. On the 14 days after starting experiment, each animal was submitted to swimming test with intensity equivalent to overload. The exhaustion was defined as a state in which coordinated movements did not return to the water surface for breathing within 10 sec. Immunohistochemistry for 5-HT, tryptophan hydroxylase (TPH), and western blot for serotonergic type 1A (5-HT1A) receptor and 5-HT transporter (5-HTT) were performed. Exhaustive swimming exercise increased 5-HT and TPH expressions in the dorsal raphe and sildenafil citrate suppressed 5-HT and TPH expressions in the exhaustive swimming exercise rats. Exhaustive swimming exercise increased 5-HT1A receptor and 5-HTT expressions in the dorsal raphe and sildenafil citrate suppressed 5-HT1A receptor and 5-HTT expressions in the exhaustive swimming exercise rats. The significant suppressing effect appeared in the 20-mg/kg sildenafil citrate. Sildenafil citrate might be proposed as a potential ergogenic aid through anticentral fatigue.

Tailored Black Phosphorus for Erythrocyte Membrane Nanocloaking with Interleukin-1α siRNA and Paclitaxel for Targeted, Durable, and Mild Combination Cancer Therapy.

Several therapeutic nanosystems have been engineered to remedy the shortcomings of cancer monotherapies, including immunotherapy (stimulating the host immune system to eradicate cancer), to improve therapeutic efficacy with minimizing off-target effects and tumor-induced immunosuppression. Light-activated components in nanosystems confer additional phototherapeutic effects as combinatorial modalities; however, systemic and thermal toxicities with unfavorable accumulation and excretion of nanoystem components now hamper their practical applications. Thus, there remains a need for optimal multifunctional nanosystems to enhance targeted, durable, and mild combination therapies for efficient cancer treatment without notable side effects. Methods: A nanosystem constructed with a base core (poly-L-histidine [H]-grafted black phosphorus [BP]) and a shell (erythrocyte membrane [EM]) is developed to offer a mild photoresponsive (near-infrared) activity with erythrocyte mimicry. In-flight electrostatic tailoring to extract uniform BP nanoparticles maintains a hydrodynamic size of <200 nm (enabling enhanced permeability and retention) after EM cloaking and enhances their biocompatibility. Results: Ephrin-A2 receptor-specific peptide (YSA, targeting cancer cells), interleukin-1α silencing small interfering RNA (ILsi, restricting regulatory T cell trafficking), and paclitaxel (X, inducing durable chemotherapeutics) are incorporated within the base core@shell constructs to create BP-H-ILsi-X@EM-YSA architectures, which provide a more intelligent nanosystem for combination cancer therapies. Conclusion: The in-flight tailoring of BP particles provides a promising base core for fabricating <200 nm EM-mimicking multifunctional nanosystems, which could be beneficial for constructing smarter nanoarchitectures to use in combination cancer therapies.

Regulatory T Cells Tailored with pH-Responsive Liposomes Shape an Immuno-Antitumor Milieu against Tumors.

Cell-based delivery platforms have received great interest in recent years and have been indicated as a promising strategy for cancer immunotherapy. Despite their wide applications in the clinical and preclinical stages, their concomitant viability and efficacy remain major issues. Herein, a strategy for harnessing regulatory T (Treg) cells is developed as an actively targeting drug-delivery system to transport drug-loaded liposomes to the desired tumor sites via conjugating liposomes on the surface of Treg cells. Under the guidance of tumor-oriented chemokines, liposome-anchored Treg cells can be leveraged to migrate and infiltrate the acidic tumor microenvironment, where pH-sensitive liposomes release the loaded cargos [comprising interleukin-2, programmed cell death ligand 1 antibody (PD-L1), and imiquimod], provoke dramatic dendritic cell maturation, block the PD-1/PD-L1 immune-checkpoint, elevate the frequency of infiltrating CD8+ effector T cells, and collectively contribute to potent inhibition of in situ and metastatic tumors. Here, the findings suggest a potential approach that offers a simple, robust, and safe insight into the tuning of Treg cells as an encouraging vector for augmenting cancer immunotherapy.

Development of Folate-Functionalized PEGylated Zein Nanoparticles for Ligand-Directed Delivery of Paclitaxel.

In this study, we investigated the active targeted delivery of a hydrophobic drug, paclitaxel (PTX), via receptor-mediated endocytosis by folate receptors expressed on cancer cells using a protein-based nanoparticle system. PTX was loaded on zein nanoparticles and conjugated with folate (PTX/Zein-FA) to estimate its chemotherapeutic efficacy in folate receptor-expressing KB cancer cells. PTX/Zein-FA nanoparticles were successfully developed, with a nanoparticle size of ~180 nm and narrow polydispersity index (~0.22). Accelerated release of PTX in an acidic environment was observed for PTX/Zein-FA. An in vitro cellular study of PTX/Zein-FAs in KB cells suggested that PTX/Zein-FA improved the cytotoxic activity of PTX on folate receptors overexpressed in cancer cells by inducing proapoptotic proteins and inhibiting anti-apoptotic proteins. In addition, PTX/Zein-FA exhibited anti-migratory properties and could alter the cell cycle profile of KB cells. A549 cells, which are folate receptor-negative cancer cells, showed no significant enhancement in the in vitro cellular activities of PTX/Zein-FA. We describe the antitumor efficacy of PTX/Zein-FA in KB tumor-bearing mice with minimum toxicity in healthy organs, and the results were confirmed in comparison with free drug and non-targeted nanoparticles.

Effects of treadmill exercise on memory and c-Fos expression in the hippocampus of the rats with intracerebroventricular injection of streptozotocin.

Alzheimer's disease is a progressive neurodegenerative disease clinically characterized by dementia and neurobehavioral deterioration. Hippocampal neurons are vulnerable to injury induced by Alzheimer's disease. The immediate early gene c-Fos has been used as a marker of neuronal activity. In the present study, we investigated the effects of treadmill exercise on long-term memory capacity and c-Fos expression in the hippocampus of rats with Alzheimer's disease. The rat model of Alzheimer's disease used in the present study was induced by the intracerebroventricular (ICV) injection of streptozotocin (STZ) using a stereotaxic instrument. The rats in the exercise group were forced to run on a treadmill for 30 min once daily for 14 consecutive days starting at 3 days after the ICV injection of STZ. The results of the present study showed that ICV injection of STZ impaired long-term memory capacity and decreased the number of c-Fos-positive cells in several regions of the rat hippocampus. However, treadmill exercise alleviated long-term memory deficits and enhanced c-Fos expression in the rats with ICV injection of STZ. The results of the present study showed that treadmill exercise could be a useful strategy for treating several neurodegenerative diseases.

Effect of postnatal treadmill exercise on c-Fos expression in the hippocampus of rat pups born from the alcohol-intoxicated mothers.

Maternal alcohol-intoxication during pregnancy exerts detrimental effects on fetal development and is known to influence learning ability and memory capability by altering neuronal activity in the hippocampus. c-Fos expression represents neuronal activity and plays a crucial role in the brain development. Physical exercise is known to enhance neuronal plasticity and activity. In the present study, we investigated the influence of postnatal treadmill running on the c-Fos expression in the hippocampus of rat pups born from the alcohol-intoxicated mothers. The results obtained show that maternal alcohol-intoxication suppressed c-Fos expression in the hippocampus of rat pups and that postnatal treadmill exercise enhanced c-Fos expression in the hippocampus of these rat pups. The present study suggests that exercise should be considered as a therapeutic means of countering the effects of maternal alcohol-intoxication, and that it may provide a useful strategy for enhancing the neuronal activity of children born from the mothers who abuse alcohol during pregnancy.

Aqueous extract of Anemarrhena rhizome increases cell proliferation and neuropeptide Y expression in the hippocampal dentate gyrus on streptozotocin-induced diabetic rats.

In this study, the effects of the aqueous extract of Anemarrhena rhizome on cell proliferation and neuropeptide Y expression in the dentate gyrus of streptozotocin-induced diabetic rats were investigated via immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU) and neuropeptide Y. The results showed that the treatment with 50 to 200 microg/kg/day for 7 days of the aqueous extract of Anemarrhena rhizome increased new cell formation and neuropeptide Y expression in the dentate gyrus of diabetic rats reduced by the treatment with streptozotocin in rat.

Late starting treadmill exercise improves spatial leaning ability through suppressing CREP/BDNF/TrkB signaling pathway following traumatic brain injury in rats.

Traumatic brain injury (TBI) causes deficit in spatial learning and memory function. Physical activity ameliorates neurological dysfunction after TBI. We investigated the effect of late starting treadmill exercise on spatial learning ability in relation with cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway using TBI rats. For this study, radial 8-arm maze test, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) staining, caspase-3 immunohistochemistry, and western blot for Bax, Bcl-2, BDNF, tyrosine kinase B (TrkB), CREB, and phosphorylated CREP (p-CREB) were performed. TBI was induced by an electromagnetic-controlled cortical impact. The rats in the exercise groups were scheduled to run on a treadmill for 30 min once a day for 8 weeks starting 3 weeks after TBI. TBI impaired spatial learning ability and increased caspase-3 expression in the hippocampal dentate gyrus. TBI enhanced Bax expression and suppressed Bcl-2 expression in the hip-pocampus. TBI increased BDNF and TrkB expressions, resulted in the enhancement of p-CREB/CREB ratio in the hippocampus. However, treadmill exercise improved spatial learning ability, decreased caspase-3 expression, suppressed Bax expression, and increased Bcl-2 expression. Treadmill exercise alleviated TBI-induced over-expression of BDNF and TrkB, which suppressed phosphorylation of CREB in the hippocampus. In the present study, late starting treadmill exercise improved spatial learning ability through suppressing TBI-induced activation of CREB/BDNF/TrkB signaling pathway after TBI.

Low-frequency electroacupncture improves locomotor function after sciatic crushed nerve injury in rats.

Sciatic crushed nerve injury (SCI) causes pain-related gait and swelling in the affected limb. Electroacupuncture (EA) is a modified acupuncture technique, and analgesic effect of EA on different types of pain has been documented. Scientific functional index (SFI) is a mathematical formula to represent parameters of normal and experimental footprints. We investigated the effect of low-frequency EA on functional recovery following SCI in rats. For this study, immunohistochemistry for c-Fos in the ventral lateral periaqueductal gray (vlPAG) and paraventricular nucleus (PVN) and western blot for neurofilament (NF) and brain-derived neurotrophic factor (BDNF) in the sciatic nerve were conducted. To induce crush injury on the sciatic nerve, sciatic nerve was crushed for 30 sec using a surgical clip. The rats in the acupuncture groups received acupuncture bilaterally at respective site, once a day for 14 days. The rats in the EA group received 100-Hz electrical stimulation for 10 min once a day during 14 days. SCI decreased SFI value, in contrast, EA increased SFI value. c-Fos expression in the vlPAG and PVN was increased following SCI, in contrast, EA suppressed c-Fos expression. NF expression in the sciatic nerve was decreased by SCI, in contrast, EA increased NF expression. BDNF expression in the sciatic nerve was increased by SCI, in contrast, EA suppressed BDNF expression. In the present study, EA showed effectiveness on functional recovery from SCI.

Treadmill exercise suppresses nigrostriatal dopaminergic neuronal loss in 6-hydroxydopamine-induced Parkinson's rats.

In Parkinson's disease, the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra leads to debilitating motor dysfunction. In the present study, we investigated the effects of treadmill exercise on the dopaminergic neuronal cell death in the substantia nigra and on the dopaminergic fiber loss in the striatum of Parkinson's rats. Parkinson's rats were made by injecting 6-hydroxydopamine into the striatum with using a stereotaxic instrument. The rats in the exercise groups were put on the treadmill to run for 30 min once a day for 14 consecutive days after 6-hydroxydopamine administration into the striatum. Two weeks after the intrastriatal injection of 6-hydroxydopamine, the rats without treadmill exercise displayed rotational asymmetry following injection of apomorphine (0.5 mg/kg, s.c.). In contrast, the rats undergoing treadmill exercise showed a significant reduction of rotational asymmetry. Analysis via immunohistochemistry for the tyrosine hydroxylase expression revealed a substantial loss of cell bodies in the substantia nigra and their projected fibers in the striatum ipsilateral to the lesion following 6-hydroxydapamine injection into the striatum. However, treadmill running enhanced the survival of dopaminergic neurons in the substantia nigra and also their fibers projecting into the striatum. The results of the present study show that treadmill exercise may provide therapeutic value for the treatment of Parkinson's disease patients.

Music application alleviates short-term memory impairments through increasing cell proliferation in the hippocampus of valproic acid-induced autistic rat pups.

Autism is a neurodevelopmental disorder and this disorder shows impairment in reciprocal social interactions, deficits in communication, and restrictive and repetitive patterns of behaviors and interests. The effect of music on short-term memory in the view of cell proliferation in the hippocampus was evaluated using valproic acid-induced autistic rat pups. Animal model of autism was made by subcutaneous injection of 400-mg/kg valproic acid into the rat pups on the postnatal day 14. The rat pups in the music-applied groups were exposed to the 65-dB comfortable classic music for 1 hr once a day, starting postnatal day 15 and continued until postnatal day 28. In the present results, short-term memory was deteriorated by autism induction. The numbers of 5-bromo-2'-deoxyridine (BrdU)-positive, Ki-67-positive, and doublecortin (DCX)-positive cells in the hippocampal dentate gyrus were decreased by autism induction. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions in the hippocampus were also suppressed in the autistic rat pups. Music application alleviated short-term memory deficits with enhancing the numbers of BrdU-positive, Ki-67-positive, and DCX-positive cells in the autistic rat pups. Music application also enhanced BDNF and TrkB expressions in the autistic rat pups. The present study show that application of music enhanced hippocampal cell proliferation and alleviated short-term memory impairment through stimulating BDNF-TrkB signaling in the autistic rat pups. Music can be suggested as the therapeutic strategy to overcome the autism-induced memory deficits.

Postnatal treadmill exercise alleviates short-term memory impairment by enhancing cell proliferation and suppressing apoptosis in the hippocampus of rat pups born to diabetic rats.

During pregnancy, diabetes mellitus exerts detrimental effects on the development of the fetus, especially the central nervous system. In the current study, we evaluated the effects of postnatal treadmill exercise on short-term memory in relation with cell proliferation and apoptosis in the hippocampus of rat pups born to streptozotocin (STZ)-induced diabetic maternal rats. Adult female rats were mated with male rats for 24 h. Two weeks after mating, the pregnant female rats were divided into two groups: control group and STZ injection group. The pregnant rats in the STZ injection group were administered 40 mg/kg of STZ intraperitoneally. After birth, the rat pups were divided into the following four groups: control group, control with postnatal exercise group, maternal STZ-injection group, and maternal STZ-injection with postnatal exercise group. The rat pups in the postnatal exercise groups were made to run on a treadmill for 30 min once a day, 5 times per week for 2 weeks beginning 4 weeks after birth. The rat pups born to diabetic rats were shown to have short-term memory impairment with suppressed cell proliferation and increased apoptosis in the hippocampal dentate gyrus. Postnatal treadmill exercise alleviated short-term memory impairment by increased cell proliferation and suppressed apoptosis in the rat pups born to diabetic rats. These findings indicate that postnatal treadmill exercise may be used as a valuable strategy to ameliorate neurodevelopmental problems in children born to diabetics.