Astrocytic glutamate transporter 1 (GLT1) deficient mice exhibit repetitive behaviors

Jia, Yun Fang; Wininger, Katheryn; Peyton, Lee; Ho, Ayy; Choi, Doo Sup

doi:10.1016/j.bbr.2020.112906

Cited by 14 publications

(11 citation statements)

References 41 publications

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“…That should not be very surprising knowing that GLT-1 accounts for more than 90% of glutamate uptake in the brain. These findings were recently confirmed by another research group [ 78 , 79 ]. Furthermore, postnatal disturbance of glia proliferation may lead to hyperactive behaviour in open field tests and alterations of social interactions in rats [ 80 ].…”

Section: Astrocytes As Important Players In the Cnssupporting

confidence: 75%

Astroglia in Autism Spectrum Disorder

Gzieło

Nikiforuk

2021

IJMS

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Autism spectrum disorder (ASD) is an umbrella term encompassing several neurodevelopmental disorders such as Asperger syndrome or autism. It is characterised by the occurrence of distinct deficits in social behaviour and communication and repetitive patterns of behaviour. The symptoms may be of different intensity and may vary in types. Risk factors for ASD include disturbed brain homeostasis, genetic predispositions, or inflammation during the prenatal period caused by viruses or bacteria. The number of diagnosed cases is growing, but the main cause and mechanism leading to ASD is still uncertain. Recent findings from animal models and human cases highlight the contribution of glia to the ASD pathophysiology. It is known that glia cells are not only “gluing” neurons together but are key players participating in different processes crucial for proper brain functioning, including neurogenesis, synaptogenesis, inflammation, myelination, proper glutamate processing and many others. Despite the prerequisites for the involvement of glia in the processes related to the onset of autism, there are far too little data regarding the engagement of these cells in the development of ASD.

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Section: Astrocytes As Important Players In the Cnssupporting

confidence: 75%

Astroglia in Autism Spectrum Disorder

Gzieło

Nikiforuk

2021

IJMS

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“…Hence, attenuated astrocytic Ca 2+ signaling decreases striatal MSN inhibition, via altered GABA levels resulting in repetitive behavior (Yu et al, 2018 ) ( Figure 5 ). Moreover, astrocytic GLT1 deficient mice show increased grooming, rearing, and jumping behavior, suggesting reduced synaptic glutamate clearance resulting in glutamatergic dysfunction underlying these behaviors (Jia et al, 2021 ). Hence, astrocytes regulate striatal activity and associated stereotypic behavior.…”

Section: Astrocytic Calcium Signaling Regulating Striatal Circuitrymentioning

confidence: 99%

Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders

Gandhi

Lee

2021

Front. Cell. Neurosci.

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Autism spectrum disorder (ASD) is comprised of several conditions characterized by alterations in social interaction, communication, and repetitive behaviors. Genetic and environmental factors contribute to the heterogeneous development of ASD behaviors. Several rodent models display ASD-like phenotypes, including repetitive behaviors. In this review article, we discuss the potential neural mechanisms involved in repetitive behaviors in rodent models of ASD and related neuropsychiatric disorders. We review signaling pathways, neural circuits, and anatomical alterations in rodent models that display robust stereotypic behaviors. Understanding the mechanisms and circuit alterations underlying repetitive behaviors in rodent models of ASD will inform translational research and provide useful insight into therapeutic strategies for the treatment of repetitive behaviors in ASD and other neuropsychiatric disorders.

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“…Serotonin and dopamine deficiency impairs the motivational circuit related to the CSTC pathway and regulates behavioral characteristics [92][93][94][95][96]. Glutamate was reduced and serotonin was elevated by 8-OH-DPAT in this study, resulting in repetitive and compulsive behavior.…”

Section: Discussionmentioning

confidence: 53%

Smo-Shh Agonist Purmorphamine Prevents Neurobehavioral and Neurochemical Defects in 8-OH-DPAT-Induced Experimental Model of Obsessive-Compulsive Disorder

et al. 2022

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Obsessive-compulsive disorder is a mental disorder characterized by repetitive, unwanted thoughts and behavior due to abnormal neuronal corticostriatal-thalamocortical pathway and other neurochemical changes. Purmorphamine is a smoothened-sonic-hedgehog agonist that has a protective effect against many neurological diseases due to its role in maintaining functional connectivity during CNS development and its anti-inflammatory and antioxidant properties. As part of our current research, we investigated the neuroprotective effects of PUR against behavioral and neurochemical changes in 8-hydroxy-2-(di-n-propylamino)-tetralin-induced obsessive-compulsive disorder in rats. Additionally, the effect of PUR was compared with the standard drug for OCD, i.e., fluvoxamine. The intra-dorsal raphe-nucleus injection of 8-OH-DPAT in rats for seven days significantly showed OCD-like repetitive and compulsive behavior along with increased oxidative stress, inflammation, apoptosis, as well as neurotransmitter imbalance. These alterations were dose-dependently attenuated by long-term purmorphamine treatment at 5 mg/kg and 10 mg/kg i.p. In this study, we assessed the level of various neurochemical parameters in different biological samples, including brain homogenate, blood plasma, and CSF, to check the drug’s effect centrally and peripherally. These effects were comparable to the standard oral treatment withfluvoxamine at 10 mg/kg. However, when fluvoxamine was given in combination with purmorphamine, there was a more significant restoration of these alterations than the individualtreatmentswithfluvoxamine and purmorphamine. All the above findings demonstrate that the neuroprotective effect of purmorphamine in OCD can be strong evidence for developing a new therapeutic target for treating and managing OCD.

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Astrocytic glutamate transporter 1 (GLT1) deficient mice exhibit repetitive behaviors

Cited by 14 publications

References 41 publications

Astroglia in Autism Spectrum Disorder

Astroglia in Autism Spectrum Disorder

Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders

Smo-Shh Agonist Purmorphamine Prevents Neurobehavioral and Neurochemical Defects in 8-OH-DPAT-Induced Experimental Model of Obsessive-Compulsive Disorder

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