Spontaneous Motor Activity Research Articles

DNA methylation profiles of transgenerational rat hyperactivity primed by silver nanoparticles: Comparison with valproate model rats of autism

There is an increasing body of evidence suggesting that a single exposure to certain chemicals can have transgenerational effects, with the underlying mechanism believed to be epigenetic. However, it remains largely unknown whether psychiatric conditions like ADHD or autism, induced by environmental chemicals, can be inherited across generations. Pregnant rats were purchased from a commercial breeder. On the 7th day of gestation (E7), they were divided into two groups: one group was orally exposed to silver nanoparticles (AgNP; 4 mg/kg), while the control group received vehicle alone. The subsequent generation (F1) underwent spontaneous motor activity (SMA) measurements at 8–11 weeks of age. For breeding at 26 weeks of age, rats with higher SMA were selected from hyperactive litters, while untreated rats were randomly selected. This process was continued for four generations in both groups. The AgNP-primed rats at 4th generation displayed significantly higher SMA, 1.8 times greater than that of untreated rats. Intraperitoneal injection of valproic acid (150 mg/kg), an epigenetic modifier to 5-day-old rats causes adult hyperactivity (1.4-fold), suggesting that epigenetic modification contributes to rat hyperactivity. Global DNA methylation profiles in the mesencephalon were positively correlated in both groups of hyperactive rats. Furthermore, there were 7–8 common genes showing both hypermethylation and hypomethylation, which are involved in neuronal development, neuronal function, transcriptional activity, DNA binding activity, cell differentiation, ubiquitination processes, or histone modification, including Pax 6 and Mecp 2. Thus, it is most likely that rats retain hyperactivity through mesencephalic DNA methylation status across transgeneration.

In Vitro and in vivo characterization of nasal pH-Responsive in-situ hydrogel of Candesartan-loaded invasomes as a potential stroke treatment.

Candesartan (CDN) is a useful anti-stroke medication because it lowers blood pressure, inflammation, oxidative stress, angiogenesis and apoptosis. However, CDN has limited efficacy due to its low solubility and poor bioavailability. This study set out to develop nasal pH-responsive in situ hydrogel of CDN-loaded invasomes a (PRHCLI) for enhancing CDN's release, penetration, bioavailability, and effectiveness as a possible treatment for stroke. Based on the results of the pre-formulation investigation, the optimum CLI formulation for intravasomal delivery of CDN was determined to be 3% of phospholipid, 0.16% of cholesterol, 3% of ethanol, and 1% of cineole. The optimum formulation significantly enhanced CDN permeation and release by 2.06-fold and 59.06%, respectively. The CLI formulation was added to a mixture of chitosan (0.67%w/v) and glyceryl monooleate (0.27%v/v) to develop PRHCLI. The PRHCLI formulation enhanced the release and permeation of CDN relative to free CDN by 2.15 and 2.76 folds, respectively. An experimental rat stroke model was utilized for in vivo studies to evaluate the bioavailability, effectiveness, and toxicity of the PRHCLI formulation. The nasal PRHCLI drops increased the CDN's bioavailability by 3.20-fold compared to oral free CDN. Increased grip strength and decreased flexion, spontaneous motor activity, and Morris Water Maze scores in comparison to oral free CDN showed that nasal PRHCLI drops have better anti-stroke activity. The toxicity evaluation revealed the safety of nasal PRHCLI. Hence, nasal PRHCLI drops may represent a promising avenue as a stroke therapy.

Impaired mitochondrial quality control in fibromyalgia: Mechanisms involved in skeletal muscle alteration

Fibromyalgia (FMS) is a persistent syndrome marked by widespread musculoskeletal pain and behavioural symptoms. Given the hypothesis linking FMS aetiology to mitochondrial dysfunction and oxidative stress, we examined the biochemical correlation among these factors by studying specific proteins associated with mitochondrial homeostasis in muscle. Additionally, this study investigated the role of Boswellia serrata gum resin extract (BS), known for its various functions, including the potent induction of antioxidant enzymes, in determining protective or reparative mechanisms in the muscle cells. Sprague–Dawley rats were injected with reserpine to induce FMS.These animals exhibited moderate changes in hind limb skeletal muscles, experiencing mobility difficulties. Additionally, there were noteworthy morphological and ultrastructural alterations, along with the expression of myogenin, mitochondrial enzymes and oxidative stress markers in the gastrocnemius muscle. Interestingly, BS demonstrated a reduction in spontaneous motor activity difficulties. Moreover, BS showed a positive impact on musculoskeletal morphostructural aspects, as well as a decrease in oxidative stress and mitochondrial alterations. In particular, BS restored the mRNA expression of citrate synthase and cytochrome-c oxidase subunit II and the activity of electron transfer chain complexes. BS also influenced mitochondrial biogenesis, upregulating PGC-1α expression and the related transcription factors (Nrf1, Tfam, Nrf2, FOXO3a, SIRT3, GCLC, NQO1, SOD2 and GPx4), oxidative stress (lipid peroxidation, GSH levels and GSH-Px activity) and mitochondrial dynamics and function (Mnf2 expression and CoQ10 levels). Overall, this study underlined the key role of the mitochondrial alteration in FMS and that BS had a very high antioxidant effect in these organelles and also in the cells.

Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature

Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

Modified Effect of Peptide Preparations on Spontaneous Motor Activity in Male Rats under the Conditions of Light Desynchronosis

This study examined the effect of peptide extracts from the epiphysis-pituitary gland of Reindeer (Rangifer tarandus) and a delta sleep-inducing peptide, simulating a modified release of drugs, on the spontaneous motor activity of male rats under the conditions of light desynchronosis. The study revealed changes in spontaneous motor activity under the influence of extracts of a peptide nature and a delta sleep-inducing peptide under the following polar light regimes. Under the conditions of constant lighting and constant darkness, an increase and a decrease in activity was observed, respectively. Under normal lighting, peptide extracts showed increased efficacy. This method of pharmacological adjustment of the body’s circadian oscillators using modified-release peptides can be used to develop a scheme for correcting light desynchronosis.

CNS DEPRESSANT ACTIVITY OF KASHAYA OF ASOKA – SARACA ASOCA ROXB. DE (WILDE.)

Ayurveda explains chikitsa (treatment – mode to attain health) as a conglomeration of chatushpada’s (four limbs). Pharmacological categorization of drugs can be explored for the first time from the Charaka Samhita, Shadvirechana Shatasriteeya Adhyaya. Asoka - Saraca asoca [Roxb] de Wilde has been included in the Vedanasthapana mahakashaya (group of drugs which alleviates a specific sensation) mentioned by Acharya Charaka, which is explained as streenam uchrokanashanaya by the Nighantukaara’s. The etymology of soka is chittavikalatha, which is a ‘lead’ to the action of a drug on “manasika bhava’s”. In clinical experience, apart from the pain, associated symptoms like nausea, vomiting, delirium, insomnia, emotional instability, nervousness, irritability, anger, and fear are also relieved by its usage. Till now, the pharmacological action of Asoka on “manasika bhava’s” remains unexplored. Hence, a preliminary experimental study has been undertaken on the reverse pharmacological aspect to assess the action of this drug on CNS. The depressant action of drugs on CNS is mediated through both neural and hormonal mechanisms. The immediate reduction in spontaneous motor activity was achieved through the neural mechanism, and the prolonged effect was achieved through the hormonal action. The drug possesses bitter principles. The functional bitter taste is expressed in brain cells by bitter taste receptors T2R’s. T2R-4, T2R-107, and T2R-38 transcripts are found in the brain stem, cerebral cortex and cerebellum. The drug is a potent source of phytoestrogen, which has oestrogen-mimicking action. The drug significantly reduces spontaneous motor activity in the CNS depressant activity study on all assessment days, with a p-value.

Non-fibril form but not fibril form of human islet amyloid polypeptide 8-20 changes brain functions in mice.

Whether fibril formation increases or decreases cytotoxicity remains unclear. Aggregation of human islet amyloid polypeptide (hIAPP), a pivotal regulator of glucose homeostasis, impairs the function and viability of pancreatic β cells. Evidence suggests that low-order oligomers of hIAPP are more toxic to β cells than fibril. However, it remains unclear whether non-fibril form of hIAPP specifically alters brain functions. This study produced fibril and non-fibril forms from a single hIAPP 8-20 peptide. The non-fibril form-injected mice showed changes in spontaneous motor activities, preference for location in the open field and social behavior. In contrast, the fibril-injected mice showed no changes in these behavioral tests. In line with the behavioral changes, the non-fibril form led to impaired neurite outgrowth of cultured neuron-like cells and the loss of neurons in the mouse hippocampus. These findings suggest that non-fibril form but not fibril form of hIAPP changes brain functions.

Functional candesartan loaded lipid nanoparticles for the control of diabetes-associated stroke: In vitro and in vivo studies

Diabetes mellitus is a metabolic disease that raises the odds of developing stroke. Candesartan has been used to prevent stroke due to its inhibitory effects on blood pressure, angiogenesis, oxidative damage, and apoptosis. However, oral candesartan has very limited bioavailability and efficacy due to its weak solubility and slow release. The study aimed to develop a nasal formulation of candesartan-loaded liposomes containing ethanol and propylene glycol (CLEP) to improve candesartan's delivery, release, permeation, and efficacy as a potential diabetes-associated stroke treatment. Using design expert software, different CLEP formulations were prepared and evaluated in vitro to identify the optimum formulation, which.The selected optimum formulation composed of 3.3% phospholipid, 10% ethanol, and 15% propylene glycol significantly increased the release and permeation of candesartan relative to free candesartan by a factor of 1.52 and 1.47, respectively. The optimum formulation significantly reduced the infarction after stroke in rats; decreased flexion, spontaneous motor activity, and time spent in the target quadrant by 70%, 64.71%, and 92.31%, respectively, and enhanced grip strength by a ratio of 2.3. Therefore, nasal administration of the CLEP formulation could be a potential diabetes-associated stroke treatment.

Inhaled Litsea glaucescens K. (Lauraceae) leaves’ essential oil has anxiolytic and antidepressant-like activity in mice by BDNF pathway activation.

Ethnopharmacological relevanceLitsea glaucescens K. (Lauraceae) is a small tree from the Mexican and Central American temperate forests, named as “Laurel”. Its aromatic leaves are ordinarily consumed as condiments, but also are important in Mexican Traditional Medicine, and among the most important non wood forest products in this area. The leaves are currently used in a decoction for the relief of sadness by the Mazahua ethnic group. Interestingly, “Laurel” has a long history. It was named as “Ehecapahtli” (wind medicine) in pre-Columbian times and applied to heal maladies correlated to the Central Nervous System, among them depression, according to botanical texts written in the American Continent almost five centuries ago. Aim of the studyDepression is the first cause of incapacity in the world, and society demands alternative treatments, including aromatherapy. We have previously demonstrated the antidepressant-like activity of L. glaucescens leaves’ essential oil (LEO), as well as their monoterpenes linalool, and beta-pinene by intraperitoneal route in a mice behavioral model. Here we now examined if LEO and linalool exhibit this property and anxiolytic activity when administered to mice by inhalation. We also investigated if these effects occur by BDNF pathway activation in the brain. Materials and methodsThe LEO was prepared by distillation with water steam and analyzed by gas chromatography-mass spectrometry (GC-MS). The monoterpenes linalool, eucalyptol and β-pinene were identified and quantified. Antidepressant type properties were determined with the Forced Swim Test (FST) on mice previously exposed to LEO or linalool in an inhalation chamber. The spontaneous locomotor activity and the sedative effect were assessed with the Open Field Test (OFT), and the Exploratory Cylinder (EC), respectively. The anxiolytic properties were investigated with the Elevated Plus Maze Apparatus (EPM) and the Hole Board Test (HBT). All experiments were video documented. The mice were subjected to euthanasia, and the brain hippocampus and prefrontal cortex were dissected. ResultsThe L. glaucescens essential oil (LEO) contains 31 compounds according to GC/MS, including eucalyptol, linalool and beta-pinene. The LEO has anxiolytic effect by inhalation in mice, as well as linalool, and β-pinene, as indicated by OFT and EC tests. The LEO and imipramine have antidepressant like activity in mice as revealed by the FST; however, linalool and ketamine treatments didn't modify the time of immobility. The BDNF was increased in FST in mice treated with LEO in both areas of the brain as revealed by Western blot; but did not decrease the level of corticosterone in plasma. The OFT indicated that LEO and imipramine didn't reduce the spontaneous motor activity, while linalool and ketamine caused a significant decrease. ConclusionHere we report by the first time that L. glaucescens leaves essential oil has anxiolytic effect by inhalation in mice, as well as linalool, and β-pinene. This oil also maintains its antidepressant-like activity by this administration way, similarly to the previously determined intraperitoneally. Since inhalation is a common administration route for humans, our results suggest L. glaucescens essential oil deserve future investigation due to its potential application in aromatherapy.

Extracts from Dendropanax morbifera leaves ameliorates cerebral ischemia-induced hippocampal damage by reducing oxidative damage in gerbil

AimIn this study, we investigated the effects of Dendropanax morbifera extract (DME) on neuroprotection against ischemic damage in gerbils. MethodsDME (100 or 300 mg/kg) was orally administered to gerbils for three weeks, and 2 h after the last DME treatment, transient forebrain ischemia in the common carotid arteries was induced for 5 min. The forebrain ischemia-related cognitive impairments were assessed by spontaneous motor activity and passive avoidance test one and four days after ischemia, respectively. In addition, surviving and degenerating neurons were morphologically confirmed by neuronal nuclei immunohistochemical staining and Fluoro-Jade C staining, respectively, four days after ischemia. Changes of glial morphology were visualized by immunohistochemical staining for each marker such as glial fibrillary acidic protein and ionized calcium-binding protein. Oxidative stress was determined by measurements of dihydroethidium, O2· (formation of formazan) and malondialdehyde two days after ischemia. In addition, glutathione redox system such as reduced glutathione, oxidized glutathione levels, glutathione peroxidase, and glutathione reductase activities were measured two days after ischemia. ResultsSpontaneous motor activity monitoring and passive avoidance tests showed that treatment with 300 mg/kg DME, but not 100 mg/kg, significantly alleviated ischemia-induced memory impairments. In addition, approximately 67 % of mature neurons survived and 29.3 % neurons were degenerated in hippocampal CA1 region four days after ischemia, and ischemia-induced morphological changes in astrocytes and microglia were decreased in the CA1 region after 300 mg/kg DME treatment. Furthermore, treatment with 300 mg/kg DME significantly ameliorated ischemia-induced oxidative stress, such as superoxide formation and lipid peroxidation, two days after ischemia. In addition, ischemia-induced reduction of the glutathione redox system in the hippocampus, assessed two days after the ischemia, was ameliorated by treatment with 300 mg/kg DME. These suggest that DME can potentially reduce ischemia-induced neuronal damage through its antioxidant properties.

The influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents

Anxiety disorders represent one of the most prevalent categories of psychiatric illnesses, affecting individuals regardless of gender, age, or social standing. They result in substantial personal and societal costs. The pursuit of novel pharmacological approaches for treating these disorders is driven by the increasing medical necessity to enhance the effectiveness and safety profiles of anxiolytic medications. Due to the fact that benzodiazepines and their derivatives have anti-anxiety, hypnotic-sedative, antidepressant, anticonvulsant, and muscle relaxant properties, they occupy a leading place in the treatment of anxiety disorders. An essential aspect of investigating the pharmacological activity of new triazolobenziazepine derivatives is assessing their impact on rodent muscle tone and coordination of movements. The aim of the work is to find out the influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents in the “vertical grid” test and coordination of movements using the rotarod test. Materials and methods. The objects of the study were 5 new derivatives of 1,2,3-triazolo-1,4-benzodiazepines. Before conducting in vivo experiments, these derivatives were mixed with lactose at a ratio of 1:1000. The “vertical grid” test and rotarod test (rotating rod test) were used to reproduce the model of motor behavior of rodents. Results. The presence of a tendency to the manifestation of a myorelaxant effect in the “vertical grid” test was established. The indicator of the total duration of detention at the facilities was similar and did not differ significantly in the control and experimental groups at doses of 0.50 mg/kg and 0.75 mg/kg. Derivatives MA-252, MA-253 and MA-254 at a dose of 1 mg/kg reduced the total duration of retention on the vertical grid, which indicates their mild muscle relaxant effect. In the rotating rod test, MA-253 derivative at a dose of 1 mg/kg increased the retention time on the rotarod, which demonstrates greater physical endurance of the animals of these experimental groups. Conclusions. The study’s findings indicated that the 1,2,3-triazolo-1,4-benzodiazepine derivatives did not exhibit an adverse impact on movement coordination. Some of these derivatives demonstrated a mild muscle relaxant effect. These results support the need for further research into their influence on spontaneous motor activity. Additionally, there’s a necessity to determine the dosage regimen, establish an effective dose, and adapt it for human use.

Chloroquine attenuates diet-induced obesity and glucose intolerance through a mechanism that might involve FGF-21, but not UCP-1-mediated thermogenesis and inhibition of adipocyte autophagy

Chloroquine diphosphate (CQ), a weak base used to inhibit autophagic flux and treat malaria and rheumatoid diseases, has been shown, through unknown mechanisms, to improve glucose and lipid homeostasis in patients and rodents. We investigate herein the molecular mechanisms underlying these CQ beneficial metabolic actions in diet-induced obese mice. For this, C57BL6/J mice fed with either a chow or a high-fat diet (HFD) and uncoupling protein 1 (UCP-1) KO and adipocyte Atg7-deficient mice fed with a HFD were treated or not with CQ (60 mg/kg of body weight/day) during 8 weeks and evaluated for body weight, adiposity, glucose homeostasis and brown and white adipose tissues (BAT and WAT) UCP-1 content. CQ reduced body weight gain and adipose tissue and liver masses in mice fed with a HFD, without altering food intake, oxygen consumption, respiratory exchange ratio, spontaneous motor activity and feces caloric content. CQ attenuated the insulin intolerance, hyperglycemia, hyperinsulinemia, hypertriglyceridemia and hypercholesterolemia induced by HFD intake, such effects that were associated with increases in serum and liver fibroblast growth factor 21 (FGF-21) and BAT and WAT UCP-1 content. Interestingly, CQ beneficial metabolic actions of reducing body weight and adiposity and improving glucose homeostasis were preserved in HFD-fed UCP-1 KO and adipocyte Atg7 deficient mice. CQ reduces body weight gain and adiposity and improves glucose homeostasis in diet-induced obese mice through mechanisms that might involve FGF-21, but not UCP1-mediated nonshivering thermogenesis or inhibition of adipocyte autophagy.

Typological Variants of Spontaneous Physical Activities, Morph Functional Status and Vegetative Homeostasis for Newborns in Late Neonatal Period

The authors present systematic interactions of spontaneous physical activities, morph functional status and vegetative homeostasis for newborns in late neonatal period. The methodological basis is conception of typological variability for physiological human individuality. There are 137 newborns (71 boys and 66 girls) in late neonatal period (10–14 days). The methods are the complex evaluation of physical child development according to the tables of centile types, the determination of spontaneous motor activity (SMA) during daily cycle, the evaluation of main cardiovascular system data and daily monitoring Heart Rate, the data of heart rhythm variability, the study of phsyco-motor status on muscles tonus basis which are responsible for reflexes and movement. The results of research show the typological variability of spontaneous physical activities among health population newborns in neonatal period and presents three functional types: children with low, medium, high spontaneous physical activities. Complex evaluation of morph functional data, vegetative homeostasis, phsyco-motor status among children with different SMA identify three variants of physiological norm for development: tonic (low SMA), harmonic (medium SMA) and kinetic (high SMA).

Modulation of chicken gut contractility by Melissa officinalis—ex vivo study

Melissa officinalis (lemon balm) has a long history of being used in traditional medicine for the treatment of gastrointestinal tract disorders in human thanks to its spasmolytic and stress reducing effects. These pharmacological properties have been confirmed in laboratory animals. Unfortunately, in the case of veterinary medicine, the effect of lemon balm on gut contractility has been never subjected to a detailed investigation. On the other hand, there is urgent need of new drugs that could be safely used in animals for both, causative and symptomatic treatment. In broiler chicken, one of the major health concerns includes gastrointestinal disorders with gut hypermotility. Thus, it is crucial to verify the potential utility of Melissa officinalis extract in gastrointestinal dysmotilities. The aim of the study was to analyze the effect of lemon balm extract and some of its active ingredients on chicken intestine motility. The study was performed on isolated proximal and distal jejunum preparations collected from broiler chicken which underwent routine slaughter procedure. The effect of lemon balm and 3 phenolic acids (rosmarinic, chlorogenic, and lithospermic) was verified under isometric conditions, toward spontaneous and acetylcholine (ACh)-induced smooth muscle activity. Surprisingly, M. officinalis turned out to be rather a myocontractile agent as it increased ACh-provoked contractility of proximal and distal jejunum strips and also intensified the spontaneous activity of distal jejunum. Only in the case of proximal intestine lemon balm extract diminished the force of spontaneous motoric activity up to approx. Sixty-seven percent of the control conditions. None of the tested phenolic acids displayed analog effect with the whole plant extract. In fact in the case of ACh-induced contractility, the acids had the opposite, that is, myorelaxant, effect than the extract, with a small exception of lithospermic acid in distal jejunum. Thus, it is impossible to assign one or more individual constituents to the effect of the whole Melissa officinalis extract. The obtained results do not support the use of lemon balm extract in broiler diseases which are accompanied by gut motility disturbances, including diarrhea.

AMPD2 plays important roles in regulating hepatic glucose and lipid metabolism

Dysregulation of hepatic glucose and lipid metabolism can instigate the onset of various metabolic disorders including obesity, dyslipidemia, insulin resistance, type 2 diabetes, and fatty liver disease. Adenosine monophosphate (AMP) deaminase (AMPD), which converts AMP to inosine monophosphate, plays a key role in maintaining adenylate energy charge. AMPD2 is the major isoform present in the liver. However, the mechanistic link between AMPD2 and hepatic glucose and lipid metabolism remains elusive. In this study, we probed into the hepatic glucose and lipid metabolism in AMPD2-deficient (A2−/−) mice. These mice exhibited reduced body weight, fat accumulation, and blood glucose levels, coupled with enhanced insulin sensitivity while maintaining consistent calorie intake and spontaneous motor activity compared with wild type mice. Furthermore, A2−/− mice showed mitigated obesity and hyper-insulinemia induced by high-fat diet (HFD) but elevated levels of the serum triglyceride and cholesterol. The hepatic mRNA levels of several fatty acid and cholesterol metabolism-related genes were altered in A2−/− mice. RNA sequencing unveiled multiple alterations in lipid metabolic pathways due to AMPD2 deficiency. These mice were also more susceptible to fasting or HFD-induced hepatic lipid accumulation. The liver exhibited elevated AMP levels but unaltered AMP/ATP ratio. In addition, AMPD2 deficiency is not associated with the adenosine production. In summary, this study established a link between purine metabolism and hepatic glucose and lipid metabolism via AMPD2, providing novel insights into these metabolic pathways.

Differential local field potential oscillations in the dorsal striatum and locomotor activity induced by morphine and haloperidol in mice.

Dopamine (DA) depletion in the dorsal striatum underlies symptoms of basal ganglia pathologies, including Parkinson's disease (PD). Various drug compounds are used to enhance DA levels for therapeutic purposes. Understanding neural signaling and movement patterns associated with over‑ and under‑stimulation of the DA system is essential. This study investigated striatal local field potential (LFP) oscillation and locomotor activity following treatments with morphine, a DA release enhancer, and haloperidol (HAL), a DA D2 receptor (D2R) antagonist in mice. After intracranial electrodes were placed into the dorsal striatum of male Swiss albino ICR mice, intraperitoneal injections of morphine or HAL were administered. LFP signals and spontaneous motor activity were recorded simultaneously. The results showed that morphine significantly increased locomotor speed, both low (30.3-44.9 Hz) and high (60.5-95.7 Hz) LFP gamma powers and delta (1-4 Hz)‑gamma (30.3-95.7 Hz) phase‑amplitude coupling. In contrast, HAL treatments were found to significantly decrease these parameters. Moreover, regression analyses also revealed significant positive correlations between locomotor speed and high gamma powers. Taken together, these results demonstrate opposite LFP oscillations in the dorsal striatum with low and high gamma activities, and delta‑gamma couplings in response to a DA release enhancer and D2R antagonist by morphine and HAL, respectively. These parameters reflect fluctuation of neuronal activity in the dorsal striatum that might be useful for pathological research and drug discovery for PD.

Mean 3D Dispersion for Automatic General Movement Assessment of Preterm Infants.

The General Movement assessment (GMA) is a validated assessment of brain maturation primarily based on the qualitative analysis of the complexity and the variation of spontaneous motor activity. The GMA can identify preterm infants presenting an early abnormal developmental trajectory before term-equivalent age, which permits a personalized early developmental intervention. However, GMA is time-consuming and relies on a qualitative analysis; these limitations restrict the implementation of GMA in clinical practice. In this study based on a validated dataset of 183 videos from 92 premature infants (54 males, 38 females) born <33 weeks of gestational age (GA) and acquired between 32 and 40 weeks of GA, we introduce the mean 3D dispersion (M3D) for objective quantification and classification of normal and abnormal GMA. Moreover, we have created a new 3D representation of skeleton joints which allows an objective comparison of spontaneous movements of infants of different ages and sizes. Preterm infants with normal versus abnormal GMA had a distinct M3D distribution (p <0.001). The M3D has shown a good classification performance for GMA (AUC=0.7723) and presented an accuracy of 74.1%, a sensitivity of 75.8%, and a specificity of 70.1% when using an M3D of 0.29 as a classification threshold.Clinical relevance- Our study paves the way for the development of quantitative analysis of GMA within the Neonatal Unit.

Protective Effect of a New Monophenolic Antioxidant TS-13 in a Mouse Model of Parkinson's Disease.

The development of means of the prevention and treatment of age-related neurodegenerative diseases, as well as geroprotectors, among other things, is based on the inflammatory and free radical theories of aging. In this context, we studied the effect of sodium monophenol 3-(3'-tert-butyl-4'-hydroxyphenyl)propyl thiosulfonate (TS-13) on the behavioral and locomotor activity of C57BL/6 mice in modeling Parkinson's disease by MPTP neurotoxin injection. TS-13 administration significantly improved orientation and exploratory activity and emotional response of the animals in the open field test, but did not affect the increase in anxiety caused by MPTP injection. Long-term (6 months) TS-13 administration did not suppress spontaneous motor activity in BALB/c mice and slightly increased their exploratory activity.

Pharmacological Evaluation of Benincasa Hispida Cogn. Fruit on Chronic Foot Shock Induced Stress in Mice

Stress can be defined as a brain-body reaction towards stimuli arising from the environment or from internal cues that are interpreted as a disruption of homeostasis. A number of reports indicated that treatment with herbal plant extracts could lead to a significant reduction in stress. The aim of this study was to evaluate the antistress activity through Inescapable electric chronic foot shock model in mice and to assess the effect of extract on stress induced behavioral changes in animals and to determine the efficiency of Benincasa hispida Cogn. Extract on Motor activity and Elevated plus maze to assess anxiety. In this study, mice were divided into five groups with five animals each. The first group received ip dose of the vehicle saline (2ml/kg). The second group received diazepam 1mg/kg ip along with foot shock. Third, fourth, and fifth groups received oral dose of 100, 200, and 400 mg /kg of fruit extract of Benincasa hispida along with foot shock. Inescapable electricFoot-shocks (intensity 0.8mA, interval: 10sec, duration:10sec) were delivered through a grid floor once daily for 21 days. The results showed that Benincasa hispida extract (200 and 400mg/kg) was found to have an antistress effect. The dose of Benincasa hispida extract (200 and 400mg/kg), increased entries into open arm and the time spend in open arm on the elevated plus maze test indicate that extract reduced the stress level and it significantly reduced the spontaneous motor activity and decreased the anxiety. The results suggest that the ethanolic extract of Benincasa hispida has potential antistress effect that can be explored for therapeutic advantage as an alternative treatment in medical conditions.

Anti-Inflammatory and Neuroprotective Effects of Standardized Fractions in Herniarin and Daphnoretin from Distictis buccinatoria.

Distictis buccinatoria is used for inflammatory-related diseases. From a dichloromethane extract were obtained five different fractions called F1 to F5, and sub-fractions F4-1, F5-1, F5-2, and F5-3; and were evaluated as anti-neuroinflammatory, antioxidant, and nootropic agents in mice exposed to lipopolysaccharide. Also, were isolated herniarin, daphnoretin, and fraction's terpenes with an anti-inflammatory activity using 12-O-tetradecanoylphorbol-13-acetate-induced auricular edema. The inhibition of local edema was: F1 (73.6 %), F2 (57 %), F3 (62.61 %), F4 (87.3 %), and F5 (93.57 %). Terpene fraction inhibited at 89.60 %, herniarin at 86.92 % (Emax 99.01 %, ED50 0.35 mg ear-1 ), and daphnoretin at 86.41 %. Fractions F4-1 and F5-2 (10 mg kg-1 ) enhancer spatial memory acquisition and spontaneous motor activity; reduced IL-1β, TNF-α, and IL-6; increased IL-10, enhanced the activity of CAT and GR. D. buccinatoria has neuroprotective activity and contains daphnoretin and herniarin, with anti-inflammatory activity.