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Autism and rats

Veronica Cartocci, Claudia Tonini, Tiziana Di Pippo, Florenzia Vuono, Sara Schiavi, Maria Marino, Viviana Trezza, Valentina Pallottini
Here, we investigated the protein network regulating cholesterol metabolism in the liver and brain of adolescent and adult male and female rats prenatally exposed to valproate (VPA), a well validated experimental model of autism spectrum disorders (ASD). We were aimed at studying whether prenatal VPA exposure affected the proteins involved in cholesterol homeostasis in a sex-dependent manner. To this aim the protein network of cholesterol metabolism, in term of synthesis and plasma membrane trafficking, was analyzed by western blot in the liver and different brain areas (amygdala, cerebellum, cortex, hippocampus, nucleus accumbens, and dorsal striatum) of adolescent and adult male and female rats prenatally exposed to VPA...
October 20, 2018: Journal of Cellular Physiology
Serena B Gumusoglu, Hanna E Stevens
Early disruptions to neurodevelopment are highly relevant to understanding both psychiatric risk and underlying pathophysiology that can be targeted by new treatments. Much convergent evidence from the human literature associates inflammation during pregnancy with later neuropsychiatric disorders in offspring. Preclinical models of prenatal inflammation have been developed to examine the causal maternal physiological and offspring neural mechanisms underlying these findings. Here we review the strengths and limitations of preclinical models used for these purposes and describe selected studies that have shown maternal immune impacts on the brain and behavior of offspring...
August 27, 2018: Biological Psychiatry
Jun Liu, Zeng-Yu Zhang, Hong Yu, Ai-Ping Yang, Ping-Fang Hu, Zhuo Liu, Min Wang
Previous studies have revealed that long noncoding RNA (lncRNA) and microRNA play a crucial role in autism, which is a childhood neurodevelopmental disorder with complicated genetic origins. Hence, the study concerns whether lncRNA C21orf121/bone morphogenetic proteins 2 (BMP2)/miR-140-5p gene network affects directed differentiation of stem cells from human exfoliated deciduous teeth (SHED) to neuronal cells in rats with autism. Autism models were successfully established. The neuron cells that differentiated from SHED cell were identified...
October 14, 2018: Journal of Cellular Biochemistry
Caihong Sun, Mingyang Zou, Ling Li, Dexin Li, Yongjuan Ma, Wei Xia, Lijie Wu, Huan Ren
Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders involving structural and functional impairment of the brain. Inwardly rectifying potassium (Kir) channels may contribute to the etiology of ASD by altering brain function. This study investigated the associations between genetic variants of KCNJ2 and KCNJ10 genes (encoding Kir2.1 and Kir4.1, respectively) and ASD risk in patients, and Kir channel expression in ASD model rats. This case-control study involved a cohort of 269 Chinese children with ASD and 243 unrelated healthy controls...
October 7, 2018: Life Sciences
Marika Matousova, Radko Soucek, Eva Tloustova, Barbora Slavikova, Hana Chodounska, Helena Mertlikova-Kaiserova, Eva Kudova
Neurosteroids are endogenous steroidal compounds that can modulate neuronal receptors. N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated, calcium-permeable ion channels that are of particular interest, as they participate in synaptic transmission and are implicated in various processes, such as learning, memory, or long-term neuronal potentiation. Positive allosteric modulators that increase the activity of NMDARs may provide a therapeutic aid for patients suffering from neuropsychiatric disorders where NMDAR hypofunction is thought to be involved, such as intellectual disability, autism spectrum disorder, or schizophrenia...
October 5, 2018: Steroids
Hanan Alfawaz, Mona Al-Onazi, Sarah I Bukhari, Manal Binobead, Nashwa Othman, Norah Algahtani, Ramesa Shafi Bhat, Nadine M S Moubayed, Haya S Alzeer, Afaf El-Ansary
Metabolites of proper fatty acids modulate the inflammatory response and are essential for normal brain development; equally, abnormal fatty acid metabolism plays a critical role in the pathology of autism. Currently, dietary supplements are often used to improve the core symptoms of Autism spectrum disorder (ASD). The present study analyzed the effects of orally supplemented omega-3 (ω-3) and vitamin B12 on ameliorating oxidative stress and impaired lipid metabolism in a propionic acid (PPA)-induced rodent model of autism, together with their effect on the gut microbial composition, where great fluctuations in the bacterial number and strains were observed; interestingly, polyunsaturated fatty acids such as omega-3 induced higher growth of the gram-positive bacterium Staphylococcus aureus and decreased the survival rates of Clostridia sp...
October 4, 2018: Journal of Molecular Neuroscience: MN
Kelly A Jones, Yue Luo, Lynn Dukes-Rimsky, Deepak P Srivastava, Richa Koul-Tewari, Theron A Russell, Lauren P Shapiro, Anand K Srivastava, Peter Penzes
Dendritic spine morphology and dendritic arborization are key determinants of neuronal connectivity and play critical roles in learning, memory and behavior function. Recently, defects of ZBTB20, a BTB and zinc finger domain containing transcriptional repressor, have been implicated in a wide range of neurodevelopmental disorders, including intellectual disability and autism. Here we show distinct effects of expression of two major isoforms, long and short, of ZBTB20, and its neurodevelopmental disorder-linked variants, on dendritic architecture of cultured rat cortical pyramidal neurons...
2018: PloS One
Corey L Kamen, Danna L Zevy, Jordan M Ward, Indra R Bishnoi, Martin Kavaliers, Klaus-Peter Ossenkopp
Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by cognitive and sensorimotor deficits, among others. Hypo-sensitivity and hyper-sensitivity to different stimuli within the same sensory modality, a prominent symptom of ASD, can be assessed by acoustic startle response (ASR) and prepulse inhibition (PPI). Propionic acid (PPA) is a short-chain fatty acid and a by-product of the human gut microbiome. Rodents treated with PPA has been found to produce ASD-related behavioral abnormalities, gastrointestinal discomfort, and conditioned aversions...
September 27, 2018: Neurotoxicity Research
Han-Fang Wu, Yi-Ju Chen, Ming-Chia Chu, Ya-Ting Hsu, Ting-Yi Lu, I-Tuan Chen, Po See Chen, Hui-Ching Lin
Deep brain stimulation (DBS) is known to be a promising treatment for resistant depression, which acts via the serotonin (5-hydroxytryptamine, 5-HT) system in the infralimbic prefrontal cortex (ILPFC). Previous study revealed that dysfunction of brain 5-HT homeostasis is related to a valproate (VPA)-induced rat autism spectrum disorder (ASD) model. Whether ILPFC DBS rescues deficits in VPA-induced offspring through the 5-HT system is not known. Using VPA-induced offspring, we therefore explored the effect of DBS in autistic phenotypes and further investigated the underlying mechanism...
September 19, 2018: International Journal of Molecular Sciences
Katie N Murray, Michelle E Edye, Maurizio Manca, Anthony C Vernon, Joanna M Oladipo, Victoria Fasolino, Michael K Harte, Varsha Mason, Ben Grayson, Patrick C McHugh, Irene Knuesel, Eric P Prinssen, Reinmar Hager, Joanna C Neill
Maternal immune activation (mIA) in rodents is rapidly emerging as a key model for neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia. Here, we optimise a mIA model in rats, aiming to address certain limitations of current work in this field. Specifically, the lack of clear evidence for methodology chosen, identification of successful induction of mIA in the dams and investigation of male offspring only. We focus on gestational and early juvenile changes in offspring following mIA, as detailed information on these critical early developmental time points is sparse...
September 12, 2018: Brain, Behavior, and Immunity
Meghraj Singh Baghel, Brijendra Singh, Yogesh Kumar Dhuriya, Rajendra Kumar Shukla, Nisha Patro, Vinay Kumar Khanna, Ishan Kumar Patro, Mahendra Kumar Thakur
Viral infection during early stage of life influences brain development and results in several neurodevelopmental disorders such as schizophrenia, autism and behavioral abnormalities. However, the mechanism through which infection causes long-term behavioral defects is not well known. To elucidate this, we have used synthetic polyinosinic-polycytidylic acid [poly (I:C)] which acts as a dsRNA molecule and interacts with toll-like receptor-3 (TLR-3) of microglia cells to evoke the immune system, thus mimicking the viral infection...
September 6, 2018: Neurobiology of Learning and Memory
Qianling Hou, Yan Wang, Yingbo Li, Di Chen, Feng Yang, Shali Wang
Although studies have investigated the role of gamma-aminobutyric acid (GABA)ergic signaling in rodent neural development and behaviors relevant to autism, behavioral ontogeny, as underlain by the changes in GABAergic system, is poorly characterized in different brain regions. Here, we employed a valproic acid (VPA) rat model of autism to investigate the autism-like behaviors and GABAergic glutamic acid decarboxylase 67 (GAD67) expression underlying these altered behaviors in multiple brain areas at different developmental stages from birth to adulthood...
2018: Frontiers in Behavioral Neuroscience
Hanan Alfawaz, Ramesa Shafi Bhat, Manar Al-Mutairi, Osima M Alnakhli, Abeer Al-Dbass, Mona AlOnazi, Majidh Al-Mrshoud, Iman H Hasan, Afaf El-Ansary
BACKGROUND: Abnormal phospholipid metabolism is a major component of many neurodevelopmental disorders including autism. Oral administration of propionic acid (PPA) can produce behavioral abnormalities and biochemical features in rodents similar to those observed in autism and can thus be used as a model to understand impaired brain fatty acid metabolism in autism. METHODS: The present study was designed to understand alterations in phospholipid metabolism in the brain of a rodent model of autism and to explore omega-3 and vitamin B12 as remedies...
August 31, 2018: Lipids in Health and Disease
Thomas Maurin, Francesca Melancia, Marielle Jarjat, Liliana Castro, Lara Costa, Sébastien Delhaye, Anouar Khayachi, Sara Castagnola, Elia Mota, Audrey Di Giorgio, Michela Servadio, Malgorzata Drozd, Gwénola Poupon, Sara Schiavi, Lara Sardone, Stéphane Azoulay, Lucia Ciranna, Stéphane Martin, Pierre Vincent, Viviana Trezza, Barbara Bardoni
The fragile X mental retardation protein (FMRP) is an RNA-binding protein involved in translational regulation of mRNAs that play key roles in synaptic morphology and plasticity. The functional absence of FMRP causes the fragile X syndrome (FXS), the most common form of inherited intellectual disability and the most common monogenic cause of autism. No effective treatment is available for FXS. We recently identified the Phosphodiesterase 2A (Pde2a) mRNA as a prominent target of FMRP. PDE2A enzymatic activity is increased in the brain of Fmr1-KO mice, a recognized model of FXS, leading to decreased levels of cAMP and cGMP...
August 23, 2018: Cerebral Cortex
Dumitru A Iacobas, Libor Velíšek
Inflammation is an established etiopathogenesis factor of infantile spasms (IS), a therapy-resistant epileptic syndrome of infancy. We investigated the IS-associated transcriptomic alterations of neurotransmission in rat hypothalamic arcuate nucleus, how they are corrected by antiinflamatory treatments and whether there are sex differences. IS was triggered by repeated intraperitoneal administration of N-methyl-D-aspartic acid following anti-inflammatory treatment (adreno-cortico-tropic-hormone (ACTH) or PMX53) or normal saline vehicle to prenatally exposed to betamethasone young rats...
October 2018: Neural Regeneration Research
Kaela E Scott, Ashley L Schormans, Katharine Y Pacoli, Cleusa De Oliveira, Brian L Allman, Susanne Schmid
Sensory processing, and auditory processing in particular, is altered in individuals with neurodevelopmental disorders such as autism spectrum disorders (ASDs). The typical maturation of the auditory system is perturbed in these individuals during early development, which may underlie altered auditory reactivity that persists in later life. Of the many genes that regulate the auditory system development, loss-of-function mutations in the CNTNAP2 gene are strongly associated with language processing deficits and ASD...
October 3, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Shivali Kohli, Madeleine V King, Stuart Williams, Adele Edwards, Theresa M Ballard, Lucinda J Steward, Daniella Alberati, Kevin C F Fone
The pituitary neuropeptide oxytocin promotes social behavior, and is a potential adjunct therapy for social deficits in schizophrenia and autism. Oxytocin may mediate pro-social effects by modulating monoamine release in limbic and cortical areas, which was investigated herein using in vivo microdialysis, after establishing a dose that did not produce accompanying sedative or thermoregulatory effects that could concomitantly influence behavior. The effects of oxytocin (0.03-0.3 mg/kg subcutaneous) on locomotor activity, core body temperature, and social behavior (social interaction and ultrasonic vocalizations) were examined in adult male Lister-hooded rats, using selective antagonists to determine the role of oxytocin and vasopressin V1a receptors...
August 7, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Adrian A Franke, Xingnan Li, Ariane Menden, Mary R Lee, Jennifer F Lai
Oxytocin (OT) is a neurohormone that has gained interest recently due to its emerging role in cognition and social/emotional behaviors, including possibly depression and autism. OT is commonly measured using enzyme- or radio-based immunoassays (RIA, ELISA), which lack specificity or are complicated to perform and involve hazardous radioactive material. We have developed a high resolution accurate-mass (HRAM) liquid chromatography-mass spectrometry (LC-MS) method that separates interferences and selectively and accurately quantitates native OT from human serum, urine, and saliva after solid phase extraction...
August 9, 2018: Drug Testing and Analysis
Hao Zhou, Weiqing Zhao, Liu Ye, Zhihe Chen, Yuxia Cui
This study aimed to explore the effects of postnatal low-concentration arsenic exposure on learning, social skills and frontal cortex neurogenesis in rats. Water-based arsenic exposure rat models were established on postnatal days 4-10 (P4-P10). The experimental animals were divided into four groups: the control group, a 15 μg/L As2 O3 water group, a 30 μg/L As2 O3 water group, and a 45 μg/L As2 O3 water group. Cognitive function was examined with the Morris water maze, anxiety-like behavior with the open field test and light-dark box test, and social skills with a social interaction test...
September 2018: Environmental Toxicology and Pharmacology
Jamela Jouda, Markus Wöhr, Adriana Del Rey
Ultrasonic vocalizations (USVs) serve important communicative functions in rodents. Different types of USVs can be triggered in the sender, for example, by maternal separation, social interactions, or exposure to predators, and they evoke affiliative or alarming behaviors in recipients. This review focusses on studies evaluating possible links between immunity and USVs. Most studies have been performed in a murine model of maternal immune activation and subsequent evaluation of effects in the offspring. This model has received large attention in recent years because it mimics behavioral abnormalities observed in certain human neuropsychiatric disorders, including autism spectrum disorder...
July 31, 2018: Annals of the New York Academy of Sciences
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