Bergmann Glia, Long-Term Depression, and Autism Spectrum Disorder

Chrobak, Adrian Andrzej; Sołtys, Zbigniew

doi:10.1007/s12035-016-9719-3

Cited by 23 publications

(18 citation statements)

References 136 publications

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“…Together these data indicated that in 16GsoT/T mice, PCs are generated in normal numbers and migrate to their final location, but do not develop normally and are lost as the animals age. This pathology is coupled to abnormalities of the Bergmann glia, the development of which is intimately linked to that of PCs (Chrobak and Soltys 2017; Yamada and Watanabe 2002).…”

Section: Resultsmentioning

confidence: 99%

A Mouse Mutation That Dysregulates NeighboringGalnt17andAuts2Genes Is Associated with Phenotypes Related to the Human AUTS2 Syndrome

Weisner

Chen

Sun

et al. 2019

G3 Genes|Genomes|Genetics

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AUTS2 was originally discovered as the gene disrupted by a translocation in human twins with Autism spectrum disorder, intellectual disability, and epilepsy. Since that initial finding, AUTS2-linked mutations and variants have been associated with a very broad array of neuropsychiatric disorders, sugg esting that AUTS2 is required for fundamental steps of neurodevelopment. However, genotype-phenotype correlations in this region are complicated, because most mutations could also involve neighboring genes. Of particular interest is the nearest downstream neighbor of AUTS2, GALNT17, which encodes a brain-expressed N-acetylgalactosaminyltransferase of unknown brain function. Here we describe a mouse (Mus musculus) mutation, T(5G2;8A1)GSO (abbreviated 16Gso), a reciprocal translocation that breaks between Auts2 and Galnt17 and dysregulates both genes. Despite this complex regulatory effect, 16Gso homozygotes model certain human AUTS2-linked phenotypes very well. In addition to abnormalities in growth, craniofacial structure, learning and memory, and behavior, 16Gso homozygotes display distinct pathologies of the cerebellum and hippocampus that are similar to those associated with autism and other types of AUTS2-linked neurological disease. Analyzing mutant cerebellar and hippocampal transcriptomes to explain this pathology, we identified disturbances in pathways related to neuron and synapse maturation, neurotransmitter signaling, and cellular stress, suggesting possible cellular mechanisms. These pathways, coupled with the translocation’s selective effects on Auts2 isoforms and coordinated dysregulation of Galnt17, suggest novel hypotheses regarding the etiology of the human “AUTS2 syndrome” and the wide array of neurodevelopmental disorders linked to variance in this genomic region.

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Section: Resultsmentioning

confidence: 99%

A Mouse Mutation That Dysregulates NeighboringGalnt17andAuts2Genes Is Associated with Phenotypes Related to the Human AUTS2 Syndrome

Weisner

Chen

Sun

et al. 2019

G3 Genes|Genomes|Genetics

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“…In Ngsk Prnp 0/0 mice, GFAP begins to increase gradually from 7 to 8 weeks of age 25 . GFAP is thought to be a significant factor needed for proper communication between Bergmann glia and PC, enabling occurrence of LTD 26 . Indeed, GFAP KO mice exhibited the impairments of cerebellar LTD and eyeblink conditioning 27 .…”

Section: Discussionmentioning

confidence: 99%

Impairment of cerebellar long-term depression and GABAergic transmission in prion protein deficient mice ectopically expressing PrPLP/Dpl

Kishimoto

Hirono

Atarashi

et al. 2020

Sci Rep

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Prion protein (PrPC) knockout mice, named as the “Ngsk” strain (Ngsk Prnp0/0 mice), show late-onset cerebellar Purkinje cell (PC) degeneration because of ectopic overexpression of PrPC-like protein (PrPLP/Dpl). Our previous study indicated that the mutant mice also exhibited alterations in cerebellum-dependent delay eyeblink conditioning, even at a young age (16 weeks of age) when neurological changes had not occurred. Thus, this electrophysiological study was designed to examine the synaptic function of the cerebellar cortex in juvenile Ngsk Prnp0/0 mice. We showed that Ngsk Prnp0/0 mice exhibited normal paired-pulse facilitation but impaired long-term depression of excitatory synaptic transmission at synapses between parallel fibres and PCs. GABAA-mediated inhibitory postsynaptic currents recorded from PCs were also weakened in Ngsk Prnp0/0 mice. Furthermore, we confirmed that Ngsk Prnp0/0 mice (7–8-week-old) exhibited abnormalities in delay eyeblink conditioning. Our findings suggest that these alterations in both excitatory and inhibitory synaptic transmission to PCs caused deficits in delay eyeblink conditioning of Ngsk Prnp0/0 mice. Therefore, the Ngsk Prnp0/0 mouse model can contribute to study underlying mechanisms for impairments of synaptic transmission and neural plasticity, and cognitive deficits in the central nervous system.

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“…Another observation in ASD is the loss of Purkinje neuron cells in the cerebellum (Becker & Stoodley, 2013;Kern, 2003;Whitney et al, 2009). Since high extracellular glutamate clearance can lead to neuronal apoptosis (Purcell et al, 2001), disruption of the Bergmann glia, which are radial astrocytes of the cerebellum, may be involved as they are responsible for maintaining extracellular glutamate homeostasis (Chrobak & Soltys, 2017).…”

Section: Neuropathologies With Underlying Functional Astrocytic Changes Regarding Inflammation Transporter Expression Synaptic Regulationmentioning

confidence: 99%

Astrocytes in rare neurological conditions: Morphological and functional considerations

et al. 2021

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Astrocytes are a population of central nervous system (CNS) cells with distinctive morphological and functional characteristics that differ within specific areas of the brain and are widely distributed throughout the CNS. There are mainly two types of astrocytes, protoplasmic and fibrous, which differ in morphologic appearance and location. Astrocytes are important cells of the CNS that not only provide structural support, but also modulate synaptic activity, regulate neuroinflammatory responses, maintain the blood–brain barrier, and supply energy to neurons. As a result, astrocytic disruption can lead to widespread detrimental effects and can contribute to the pathophysiology of several neurological conditions. The characteristics of astrocytes in more common neuropathologies such as Alzheimer's and Parkinson's disease have significantly been described and continue to be widely studied. However, there still exist numerous rare neurological conditions in which astrocytic involvement is unknown and needs to be explored. Accordingly, this review will summarize functional and morphological changes of astrocytes in various rare neurological conditions based on current knowledge thus far and highlight remaining neuropathologies where astrocytic involvement has yet to be investigated.

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Bergmann Glia, Long-Term Depression, and Autism Spectrum Disorder

Cited by 23 publications

References 136 publications

A Mouse Mutation That Dysregulates NeighboringGalnt17andAuts2Genes Is Associated with Phenotypes Related to the Human AUTS2 Syndrome

A Mouse Mutation That Dysregulates NeighboringGalnt17andAuts2Genes Is Associated with Phenotypes Related to the Human AUTS2 Syndrome

Impairment of cerebellar long-term depression and GABAergic transmission in prion protein deficient mice ectopically expressing PrPLP/Dpl

Astrocytes in rare neurological conditions: Morphological and functional considerations

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