Abstract
Astrocytes are highly involved in regulation and homeostasis of the extracellular environment in the healthy brain. In pathological conditions, these cells play a major role in the inflammatory response seen in CNS tissues, which is called reactive astrogliosis and includes hypertrophy and proliferation of astrocytes. Here, we performed 3D confocal microscopy to evaluate the morphological response of reactive astrocytes positive for glial fibrillary acidic protein (GFAP) in rats, to the presence of Aβ1–40 in the rat brain before and after treatment with genistein. In 50 astrocytes per animal, we measured the volume and surface area for the nucleus, cell body, the entire cell, the tissue covered by single astrocytes and quantified the number and length of branches, the density of the astrocytes and the intensity of GFAP immunoreactivity. Injecting Aβ1–40 into the brain of rats caused astrogliosis indicated by increased values for all measured parameters. Mass spectrometric analysis of hippocampal tissue in Aβ1–40-injected brain showed decreased amounts of tubulins, enolases and myelin basic protein, and increased amounts of dihydropyrimidinase-related protein 2. In Aβ1–40-injected rats pretreated with genistein, GFAP intensity was decreased to the sham-operated group level, and Aβ1–40-induced astrogliosis was significantly ameliorated.
Highlights
Astrocytes are highly involved in the regulation of extracellular ion and neurotransmitter homeostasis in the healthy brain [1,2,3,4] and failure of astrocyte-dependent homeostasis leads to imbalance in neurotransmission in a wide range of diseases [5]
The occurrence of glial fibrillary acidic protein (GFAP)+ astrocytes increased from layer 1 towards layer 6 of the cortex and was most intense in corpus callosum and the polymorphic layer of the hippocampus (Figure 1B)
The cornuammonis 1 (CA1) subfield contained few GFAP+ astrocytes with long branches, and the cornuammonis 2 (CA2) subfield displayed a dense network of small astrocytes with overlapping short branches
Summary
Astrocytes are highly involved in the regulation of extracellular ion and neurotransmitter homeostasis in the healthy brain [1,2,3,4] and failure of astrocyte-dependent homeostasis leads to imbalance in neurotransmission in a wide range of diseases [5]. Astrocytes play a pivotal role in the modulation of synaptic plasticity that is important for mechanisms of cognition, learning, and memory [6,7] These glia cells respond to harmful stimuli by changing their molecular, cellular, and functional properties. Garwood and colleagues [11] recently observed that Aβ-induced neuronal death was accelerated by the presence of astrocytes in primary culture, and this neuronal loss was reduced when astrocyte activation was inhibited by treatment with an antiinflammatory drug. Such drugs have been used in patients as a therapeutic approach to delay the progression of AD, but, they have not achieved the desired effects. Knowledge regarding the role of astrogliosis in AD is limited
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
