Bergmann Glia LongTerm Depression and Autism Sp

Authors: Adrian Andrzej Chrobak Zbigniew Soltys

Publish Date: 2016/01/26

Volume: 54, Issue: 2, Pages: 1156-1166

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Abstract

Bergmann glia BG a specific type of radial astrocytes in the cerebellum play a variety of vital functions in the development of this structure However the possible role of BG in the development of abnormalities observed in individuals with autism spectrum disorder ASD seems to be underestimated One of the most consistent findings observed in ASD patients is loss of Purkinje cells PCs Such a defect may be caused by dysregulation of glutamate homeostasis which is maintained mainly by BG Moreover these glial cells are involved in longterm depression LTD a form of plasticity which can additionally subserve neuroprotective functions The aim of presented review is to summarize the current knowledge about interactions which occur between PC and BG with special emphasis on those which are relevant to the survival and proper functioning of cerebellar neuronsThe cerebellum is well known for its role in motor behavior Moreover there is growing evidence that this part of the brain is involved in various cognitive and affective processes 1 2 and that its dysfunctions may be linked to various psychiatric disorders 3 including autism spectrum disorder ASD 4 5The characteristic features of this syndrome such as deficit in social interactions or hypersensitivity to sensory stimuli 6 indicate the cerebral cortex as a potential locus of pathology Nevertheless significant anatomical pathology can also be seen in the cerebellum of ASD patients including a reduction in the total volume atrophy of the folia 7 8 and small foci of dysplasia 9 Loss of Purkinje cells PCs the principal neurons in the cerebellum is the most consistent cellular abnormality found in ASD 10 11 Importantly this deficit has not resulted from decreased proliferation but from the loss of the PC in the later stages of development 12Bergmann glia BG is a type of radial glia specific for the cerebellum While BG somata are localized in the Purkinje cell layer their processes form a dense palisade extending through molecular layer of the cortex Similar to protoplasmic astrocytes in other parts of the brain BG processes cover synapses on Purkinje neuron dendrites 13 what suggests its participation in the regulation of synaptic transmission Paradoxically BG is the most ignored population of cerebellar cells It is hard to find these cells in the textbook diagrams depicting the structure of the cerebellar cortex connections Although each PC is linked to BG the number of publications related to this glia is only 5–6  of those on PC according to Pubmed and Google Scholar searchIn this paper we will present arguments in favor of the hypothesis that abnormalities in the interaction between BG and PC may lead to the emergence of autism spectrum disorders First of all we will briefly summarize our knowledge about the role of BG in the development and maintenance of the proper functioning of the cerebellum with particular focus on glutamatergic transmission Then we will discuss the involvement of these cells in longterm depression LTD This phenomenon is usually regarded as a basic mechanism of cerebellardependent learning however it was also proposed that LTD serves a neuroprotective functions 14 In the last part we consider the possible causes of abnormal interactions between cerebellar cells and the effects of these anomalies for the functioning of the entire brainOn the other hand BG requires continuous association with PC for the development of its own normal phenotype For example the presence of PC is necessary to maintain high levels of snglycerol3phosphate dehydrogenase—an enzyme involved in several metabolic pathways including lipid synthesis and energy metabolism 21 Dynamic transformation of BG fibers and the expression of the glutamate transporter GLAST correlate with dendritic outgrowth and synapse formation of cerebellar PC 22 Neuronderived fibroblast growth factor 9 neuronspecific Delta/Notchlike EGFrelated receptor and sonic hedgehog protein are vital for mediating neuronglia interaction and promote differentiation of BG and its GLAST expression 23 24 25 26

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