Astrocytes conspire with neurons during progression of neurological disease
ABSTRACT As astrocytes are becoming recognized as important mediators of normal brain function, studies into their roles in neurological disease have gained significance. Across mouse models for neurodevelopmental and neurodegenerative diseases, astrocytes are considered key regulators of disease progression. In Rett syndrome and Parkinson's disease, astrocytes can even initiate certain disease phenotypes. Numerous potential mechanisms have been offered to explain these results, but research into the functions of astrocytes in disease is just beginning. Crucially, in vivo verification of in vitro data is still necessary, as well as a deeper understanding of the complex and relatively unexplored interactions between astrocytes, oligodendrocytes, microglia, and neurons.
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ABSTRACT: A growing body of research indicates a pivotal role for astrocytes at the developing synapse. In particular, astrocytes are dynamically involved in governing synapse structure, function, and plasticity. In the postnatal brain, their appearance at synapses coincides with periods of developmental plasticity when neural circuits are refined and established. Alterations in the partnership between astrocytes and neurons have now emerged as important mechanisms that underlie neuropathology. With overall synaptic function standing as a prominent link to the expression of the disease phenotype in a number of neurodevelopmental disorders and knowing that astrocytes influence synapse development and function, this paper highlights the current knowledge of astrocyte biology with a focus on their involvement in fragile X syndrome.Neural Plasticity 07/2012; 2012(2090-5904):197491. DOI:10.1155/2012/197491 · 3.60 Impact Factor
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ABSTRACT: Recent studies have implicated potentially significant roles for astrocytes in the pathogenesis of neurodevelopmental disorders. Astrocytes undergo a dramatic maturation process following early differentiation from which typical morphology and important functions are acquired. Despite significant progress in understanding their early differentiation, very little is known about how astrocytes become functionally mature. In addition, whether functional maturation of astrocytes is disrupted in neurodevelopmental disorders and the consequences of this disruption remains essentially unknown. In this review, we discuss our perspectives about how astrocyte developmental maturation is regulated, and how disruption of the astrocyte functional maturation process, especially alterations in their ability to regulate glutamate homeostasis, may alter synaptic physiology and contribute to the pathogenesis of neurodevelopmental disorders.Journal of Neurodevelopmental Disorders 08/2013; 5(1):22. DOI:10.1186/1866-1955-5-22 · 3.71 Impact Factor
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ABSTRACT: In the present study, we investigated the effects of hypothyroidism on the morphology of astrocytes and microglia in the hippocampus of Zucker diabetic fatty rats and Zucker lean control rats. To induce hypothyroidism, Zucker lean control and Zucker diabetic fatty rats at 7 weeks of age orally received the vehicle or methimazole, an anti-thyroid drug, treatment for 5 weeks and were sacrificed at 12 weeks of age in all groups for blood chemistry and immunohistochemical staining. In the methimazole-treated Zucker lean control and Zucker diabetic fatty rats, the serum circulating thyronine (T3) and thyroxine (T4) levels were significantly decreased compared to levels observed in the vehicle-treated Zucker lean control or Zucker diabetic fatty rats. This reduction was more prominent in the methimazole-treated Zucker diabetic fatty group. Glial fibrillary acidic protein immunoreactive astrocytes and ionized calcium-binding adapter molecule 1 (Iba-1)-immunoreactive microglia in the Zucker lean control and Zucker diabetic fatty group were diffusely detected in the hippocampal CA1 region and dentate gyrus. There were no significant differences in the glial fibrillary acidic protein and Iba-1 immunoreactivity in the CA1 region and dentate gyrus between Zucker lean control and Zucker diabetic fatty groups. However, in the methimazole-treated Zucker lean control and Zucker diabetic fatty groups, the processes of glial fibrillary acidic protein tive astrocytes and Iba-1 immunoreactive microglia, were significantly decreased in both the CA1 region and dentate gyrus compared to that in the vehicle-treated Zucker lean control and Zucker diabetic fatty groups. These results suggest that diabetes has no effect on the morphology of astrocytes and microglia and that hypothyroidism during the onset of diabetes prominently reduces the processes of astrocytes and microglia.Neural Regeneration Research 09/2013; 8(26):2458-67. DOI:10.3969/j.issn.1673-5374.2013.26.007 · 0.23 Impact Factor