Epigallocatechin-3-gallate as a modulator of motor coordination, repetitive behavior, and sensory function in autism spectrum disorder

Background:The cause of autism spectrum disorder (ASD) is currently still unclear. Research on the etiology and biomolecular aspects of autism is needed to develop further prevention and therapy strategies. Animal models of autism are needed for further research.Aim:This study aimed to investigate the effect of valproic acid administration on motor coordination and sensory function in Mus musculus as an animal model of autism.Methods:This study used M. musculus that were ready to be mated and waited until they were pregnant. Randomization was carried out using the website random.org, and the participants were divided into two groups: the control and experimental groups. On embryo day 12.5, the control group was injected intraperitoneally with normal saline, and the experimental group was injected intraperitoneally with 600 mg/kg body weight of valproic acid. The offspring of the mice underwent autism symptom behavior test, motor coordination, and pain response.Results:There were significant differences in the negative geotropism test and hot plate test between the control and experimental groups (p < 0.05). The experimental group that was intraperitoneally injected with valproic acid takes longer to reorient on an inclined plane as part of motor coordination skills. The experimental group also provided a longer response time to heat stimuli on a hot plate, indicating an abnormal response to pain stimuli.Conclusion:Intraperitoneally injected M. musculus with valproic acid showed symptoms of autism, especially disorders in motor coordination and response to pain stimuli.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social deficits, restricted interests, and repetitive behaviors. Although aripiprazole and risperidone are FDA-approved for ASD, they primarily target comorbid symptoms and are associated with significant side effects. This study aimed to investigate the effects of 6-bromoindirubin-3'-oxime (6BIO), a glycogen synthase kinase 3β (GSK3β) inhibitor, in a VPA model of ASD. Pregnant Wistar rat dams received a single intraperitoneal (ip) injection of VPA (600 mg/kg) or an equal volume of saline on GD 12.5. Offspring prenatally exposed to VPA showed impairments in early age observations, such as nervous reflex, motor coordination, sensory function, and developmental milestones. On postnatal day (PND), 23 male and female offspring were separated and randomly assigned to receive either risperidone (2.5 mg/kg, po) or 6BIO (15 or 30 μg/kg, ip) daily until PND 82. Systemic postnatal administration of 6BIO dose-dependently ameliorated anxiety-like behavior, exploratory, social deficit, repetitive behavior, spatial cognition, recognition memory, motor coordination, gastrointestinal motility, brain edema, and blood-brain barrier functions. Furthermore, chronic 6BIO postnatal treatment significantly attenuated VPA-induced neuronal damage in the prefrontal cortex, hippocampus, and cerebellum. 6BIO also significantly suppressed the upregulated cytosolic GSK3β phosphorylation, as determined by immunohistochemistry and Western blotting. Additionally, 6BIO modulated mRNA expression levels of Wnt, CHD8, SHANK3, GAD65, and 67, and transcriptional factors such as β-catenin and NLGN3 were altered by prenatal VPA exposure. In conclusion, these findings suggest that 6BIO may exert neuroprotective effects via GSK3β inhibition, indicating its potential as a candidate compound for therapeutic intervention in ASD.

Prenatal alcohol exposure (PAE) refers to fetal exposure to alcohol during pregnancy through placental barrier transfer from maternal blood. The postnatal outcomes of PAE differ among exposed individuals and range from overt (serious) alcohol-related behavioral and neurophysiological impairments to covert (silenced) symptoms. The aims of the present investigation were to assess the postnatal neurobehavioral disturbances, particularly, motor coordination and sensory-motor function in mice with PAE. Female mice with positive vaginal plugs were divided into three groups: group 1: Et + Pyr: received two i.p injections of ethanol (1 g/kg) followed by pyrazole (100 mg/kg). Group 2: Pyr: received an i.p injection of pyrazole (100 mg/kg). Group 3: C: of saline controls received, in equal volume, saline solution (NaCl 0.9%). After birth, mice pups were weighed and subjected to behavioral tests for motor function screening using the motor ambulation test, cliff aversion, surface righting, and negative geotaxis, while at the adult stage, mice were subjected to the open field, rotarod, parallel bars, and static rods tests. Our data show an obvious decrement of body weight from the first post-natal day (P1) and continues over the adult stage. This was accompanied by an obvious impaired sensory-motor function which was maintained even at the adult stage with alteration of the locomotor and coordination abilities. The current data demonstrate the powerful neurotoxic effect of prenatal ethanol exposure on the sensory-motor and coordination functions, leading to suppose possible structural and/or functional neuronal disturbances, particularly the locomotor network.

Special Report: Autism Spectrum Disorder and Inflexible Thinking—Affecting Patients Across the Lifespan

Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation. Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6-30years), cognitive ability (60-140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil-dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures. We observed decreased saccade duration (∆M=-0.50, CI [-0.21, -0.78]) and amplitude (∆M=-0.42, CI [-0.12, -0.72]), which was independent of human video content. We observed null findings concerning fixation and pupil-dilation features (POWER=.81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior. We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo-)motor coordination and attention function in ASD.

Abstract: MSG can caused obesity that can affect metabolism in the body. The administration of EGCG can increase energy expenditure and metabolism. This study aimed to determine the effect of epigallocatechin 3-gallate (EGCG) on body weight and the percentage of abdominal fat of white rats (Rattus norvegicus) exposed to monosodium glutamate (MSG). Twenty-five rats were divided into five treatment groups. The C- group was given only aquadest and Sodium carboxymethyl cellulose (CMC-Na) 1%. The C+, T1, T2, and T3 groups were given MSG 120 mg/kg/BW and CMC-Na 1%, and EGCG at 4, 8, and 16 mg/kg/BW, respectively. All treatments were given orally for 28 days. The results showed that administration of MSG tends to be followed by an increase in body weight, except in group T2 where body weight was relatively stable. The administration of MSG 120 (to the C+ group) increased significantly (p&lt;0.05) the percentage of epididymal fat and peritoneal fat. The administration of EGCG 8 (to the T2 group) significantly reduced (p&lt;0.05) the percentage of retroperitoneal, epididymal, and peritoneal fat, compared to the group exposed to (C+ group). The percentage of retroperitoneal fat and epididymal fat was significantly lower (p&lt;0.05), but the percentage of peritoneal fat was not significantly different (p&gt;0.05) compared to normal mice (C-). The administration of EGCG 16 (to the T3 group) followed a significant increase (p&lt;0.05) in retroperitoneal fat and epididymal fat, but the percentage of peritoneal fat was not significantly different (p&gt;0.05), compared to (T2 group). It could be concluded that the administration of EGCG 8 mg/kg BW/day reduced the weight of retroperitoneal fat, epididymal fat, and peritoneal fat compared to mice given MSG alone. This research is expected to become the main reference for product processed from the substance EGCG which can reduce body weight and abdominal fat. Keywords: cardiovascular disease, epididymal, obesity, peritoneal, retroperitoneal.

This study examined the neuropsychological functioning in autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and comorbid ASD and ADHD (ASD + ADHD), using five domains of the Developmental Neuropsychological Assessment (NEPSY): Attention and Executive Functions, Language, Visuospatial Processing, Sensorimotor Functions, and Memory and Learning. The participants were 6- to 12-year-old Egyptian children with ASD (n = 17), ASD + ADHD (n = 15), ADHD (n = 37), and typical development (TD; n = 29). TD children scored highest on the NEPSY domains, then children with ADHD, followed by children with ASD and ASD + ADHD. Children with ASD or ASD + ADHD performed significantly poorer than TD children on all NEPSY domains. Children with ADHD exhibited significantly poorer performance than TD children on NEPSY domains of Attention and Executive Function, Language, and Memory and Learning. Also, both ASD and ASD + ADHD groups scored significantly lower than ADHD group on all other NEPSY domains except Visuospatial Processing. There were no significant differences between ASD and ASD + ADHD groups on NEPSY. Compared to TD children, our results suggest that ADHD symptoms in children with ASD may worsen the ability to plan, hand motor coordination, and memorizing names. Nevertheless, the presence of ADHD symptoms may mitigate the difficulties that children with ASD exhibit in other neuropsychological areas, such as verbal fluency, hand praxis, finger gnosis, and face memory.

Autism spectrum disorder, one of the most common neurodevelopmental disorders, is a lifelong condition, especially with difficulties in social communication, limited interest, and repetitive behavior. Working memory, as a basic executive function, is a cognitive process also associated with impulse control, inhibition, organization, mental flexibility, focusing on one&#039;s attention, planning, responding to new situations, initiating and monitoring actions, problem solving, and goal-directed behaviors. Studies suggest that working memory impairments are associated with repetitive behaviors, and the risk for academic failure observed in autism spectrum disorder, and other neurodevelopmental disorders. From this point of view, working memory deficits are often found in neurodevelopmental disorders, especially in autism spectrum disorder. In the current study, following an introduction to autism and working memory, working memory functions associated with autism spectrum disorder were reviewed in detail. In this context, brain imaging studies highlighting the importance of frontal lobe functions, links between repetitive behaviors and working memory, and age differences in working memory functions were summarized. Next, working memory deficits in other neurodevelopmental disorders, such as attention deficit/hyperactivity disorder and pervasive developmental disorder were discussed in comparison with autism. Finally, the conclusion part of the current review tried to provide a contribution to future studies.

Background: Chronic hypertension during pregnancy is a significant concern, associated with increased risks of maternal-fetal morbidity and mortality. Epigallocatechin gallate (EGCG), a compound known for its cardioprotective properties, has gained attention as a potential health supplement due to its favorable safety profile. Objective: This study aims to investigate the effects of maternal EGCG supplementation on elevated blood pressure and pregnancy outcomes in a rodent model of chronic hypertension, specifically using spontaneously hypertensive rats (SHR). Furthermore, the study explores the influence of maternal EGCG supplementation on the blood pressure of SHR offspring during early postnatal development. Methods: SHR dams received oral EGCG at 30 mg/kg body weight. Systolic blood pressure (SBP) monitored weekly throughout gestation period and until postpartum day 21. Pregnancy outcomes - litter size, pup viability, and birth weights - were recorded. SBP in weaned SHR offspring was monitored from 5 to 13 weeks of age to assess long-term effects of maternal EGCG treatment. Daily cage-side observations evaluated general health, behavior, and signs of toxicity. Plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine were analyzed to evaluate liver and kidney function. Results: EGCG treatment in SHR dams progressively reduced maternal SBP throughout gestation and the postpartum period. However, EGCG administration did not affect pregnancy outcomes (gestation duration, litter size, and birth weights). Markers of liver and kidney function (ALT, AST, urea, and creatinine) showed no signs of organ injury in EGCG-treated groups. Contrary to expectations, SBP in SHR offspring exposed to perinatal EGCG did not decrease compared to control groups, indicating maternal EGCG did not alter the offspring's hypertension predisposition. Conclusion: Maternal EGCG supplementation effectively lowered blood pressure in hypertensive dams without compromising pregnancy outcomes or causing liver and kidney damage. These findings suggest that EGCG may be a safe cardioprotective supplement during pregnancy. However, perinatal EGCG exposure did not alter the inherent genetic predisposition to hypertension in SHR offspring. Keywords: Theaceae; Camellia sinensis; green tea; catechins, EGCG; hypertension, pregnancy outcomes, perinatal, spontaneously hypertensive rats, chronic hypertension during pregnancy

Heightened interest in sensory function in persons with autism spectrum disorder (ASD) presents an unprecedented opportunity for impactful, interdisciplinary work between neuroscientists and clinical practitioners for whom sensory processing is a focus. In spite of this promise, and a number of overlapping perspectives on sensory function in persons with ASD, neuroscientists and clinical practitioners are faced with significant practical barriers to transcending disciplinary silos. These barriers include divergent goals, values, and approaches that shape each discipline, as well as different lexical conventions. This commentary is itself an interdisciplinary effort to describe the shared perspectives, and to conceptualize a framework that may guide future investigation in this area. We summarize progress to date and issue a call for clinical practitioners and neuroscientists to expand cross-disciplinary dialogue and to capitalize on the complementary strengths of each field to unveil the links between neural and behavioral manifestations of sensory differences in persons with ASD. Joining forces to face these challenges in a truly interdisciplinary way will lead to more clinically informed neuroscientific investigation of sensory function, and better translation of those findings to clinical practice. Likewise, a more coordinated effort may shed light not only on how current approaches to treating sensory processing differences affect brain and behavioral responses to sensory stimuli in individuals with ASD, but also on whether such approaches translate to gains in broader characteristics associated with ASD. It is our hope that such interdisciplinary undertakings will ultimately converge to improve assessment and interventions for persons with ASD. Autism Res 2016, 9: 920-925. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

The postsynaptic side of excitatory synapses contains multiprotein complexes, termed the postsynaptic density, which contains receptors, scaffolding/adaptor proteins, and signaling molecules. Shank2 is an excitatory postsynaptic scaffolding protein implicated in the formation and functional coordination of the postsynaptic density and has been linked to autism spectrum disorders. Using Shank2-null mice and Shank2-conditional knock-out mice with a gene deletion restricted to cerebellar Purkinje cells, we explored functions of Shank2 in the cerebellum. We found that Shank2 regulates excitatory synapse density, motor coordination, and specific repetitive and anxiety-like behaviors, but is not associated with autistic-like social deficits or repetitive behaviors.

To investigate the absorption and metabolism of an anticarcinogenic tea catechin, (-)-epigallocatechin-3-gallate (EGCg), in rats, a newly developed chemiluminescence-detection high-performance liquid chromatography (CL-HPLC) method was employed and the EGCg concentrations in blood plasma, liver, brain, small intestinal mucosa and colon mucosa were determined before and after EGCg administration. The recovery of EGCg, extracted consecutively with ethyl acetate and methanol, was 86.1% from plasma and 64.5-74.2% from the tissue samples. The EGCg concentrations of plasma and tissue samples from the control rat (before EGCg administration) were all below the detection limit (< 0.002 nmol/mL, 0.002 nmol/g), but 60 min after a single oral administration of EGCg (500 mg/kg body weight), the levels increased, reaching 12.3 nmol/mL in plasma, 48.4 nmol/g in liver, 0.5 nmol/g in brain, 565 nmol/g in small intestinal mucosa and 68.6 nmol/g in colon mucosa. The EGCg levels found in the tissues corresponded to 0.0003-0.45% of ingested EGCg. The results indicate that tea catechin, EGCg, is absorbed from the digestive tract, with the intestinal mucosa the most enriched of the organelles. This may explain the potent antioxidant function of EGCg in inhibiting colon mucosal phospholipid hydroperoxidation in the prevention of rat colonic carcinogenesis.

This study examines the influence of ascorbic acid pretreatment on ethanol clearance, toxicity, and behavioral impairment after an acute dose of ethanol in humans. Ascorbic acid or a placebo was given to 20 healthy male subjects for 2 weeks before ethanol consumption. The dose of ethanol was 0.95 gm/kg body weight and was consumed during a 2 1/2-hour period. Thirty minutes after ethanol consumption, motor coordination and intellectual function were assessed by Goldberg's "Finger-Finger" and "Serial Sevens" tests. In addition, color discrimination was measured with the use of the Farnsworth-Munsell 100 Hue Color Test. Hourly blood samples were taken for 10 hours after ethanol consumption to measure serum triglyceride levels, blood lactate/pyruvate ratios, and serum enzymes. Blood ethanol clearance was also determined. Ethanol consumption elevated serum triglyceride levels and blood lactate/pyruvate ratios and impaired performance of the behavioral tests but did not alter serum enzyme levels. Ascorbic acid pretreatment resulted in significant enhancement in blood ethanol clearance and an increase in serum triglyceride levels after ethanol consumption in half of the subjects. Ascorbic acid pretreatment also resulted in improved motor coordination and color discrimination after ethanol consumption in half of the subjects. Ascorbic acid pretreatment did not influence elevated blood lactate/pyruvate ratios or impaired intellectual function.

Environmental exposure to sodium fluoride (NaF) compounds is a worldwide health concern. Epigallocatechin gallate (EGCG) is a green tea catechin found in a variety of green tea preparations. The intention of this study was to investigate the hepatoprotective role of EGCG in NaF-intoxicated rats. Rats were orally treated with NaF alone (25 mg·(kg body mass)(-1)·day(-1)) or plus EGCG at different doses (20, 40, and 80 mg·(kg body mass)(-1)·day(-1)) for 4 weeks. Hepatotoxicity of NaF was determined by increased levels of serum hepatospecific markers and total bilirubin, along with increased levels of thiobarbituric acid reactive substances, lipid hydroperoxides, protein carbonyl content, and conjugated dienes. The hepatotoxic nature of NaF was further evidenced by the decreased activity of enzymatic and nonenzymatic antioxidant levels in liver. NaF-treated rats also showed increased DNA damage and fragmentation in hepatocytes. Administration of EGCG (40 mg·(kg body mass)(-1)) to NaF-intoxicated rats significantly recuperated the distorted biochemical indices, DNA damage, and pathological changes in the liver tissue. Thus, the results of the present study clearly demonstrate that EGCG has strong free radical scavenging, antioxidant, and antigenotoxic properties that protect against NaF-induced oxidative hepatic injury in rats.

Environmental exposure to sodium fluoride (NaF) compounds is a worldwide health concern. Epigallocatechin gallate (EGCG) is a green tea catechin found in a variety of green tea preparations. The intention of this study was to investigate the hepatoprotective role of EGCG in NaF-intoxicated rats. Rats were orally treated with NaF alone (25 mg·(kg body mass)(-1)·day(-1)) or plus EGCG at different doses (20, 40, and 80 mg·(kg body mass)(-1)·day(-1)) for 4 weeks. Hepatotoxicity of NaF was determined by increased levels of serum hepatospecific markers and total bilirubin, along with increased levels of thiobarbituric acid reactive substances, lipid hydroperoxides, protein carbonyl content, and conjugated dienes. The hepatotoxic nature of NaF was further evidenced by the decreased activity of enzymatic and nonenzymatic antioxidant levels in liver. NaF-treated rats also showed increased DNA damage and fragmentation in hepatocytes. Administration of EGCG (40 mg·(kg body mass)(-1)) to NaF-intoxicated rats significantly recuperated the distorted biochemical indices, DNA damage, and pathological changes in the liver tissue. Thus, the results of the present study clearly demonstrate that EGCG has strong free radical scavenging, antioxidant, and antigenotoxic properties that protect against NaF-induced oxidative hepatic injury in rats.