Astroglia-Microglia Cross Talk during Neurodegeneration in the Rat Hippocampus

Abstract

Brain injury triggers a progressive inflammatory response supported by a dynamic astroglia-microglia interplay. We investigated the progressive chronic features of the astroglia-microglia cross talk in the perspective of neuronal effects in a rat model of hippocampal excitotoxic injury. N-Methyl-D-aspartate (NMDA) injection triggered a process characterized within 38 days by atrophy, neuronal loss, and fast astroglia-mediated S100B increase. Microglia reaction varied with the lesion progression. It presented a peak of tumor necrosis factor-α (TNF-α) secretion at one day after the lesion, and a transient YM1 secretion within the first three days. Microglial glucocorticoid receptor expression increased up to day 5, before returning progressively to sham values. To further investigate the astroglia role in the microglia reaction, we performed concomitant transient astroglia ablation with L-α-aminoadipate and NMDA-induced lesion. We observed a striking maintenance of neuronal death associated with enhanced microglial reaction and proliferation, increased YM1 concentration, and decreased TNF-α secretion and glucocorticoid receptor expression. S100B reactivity only increased after astroglia recovery. Our results argue for an initial neuroprotective microglial reaction, with a direct astroglial control of the microglial cytotoxic response. We propose the recovery of the astroglia-microglia cross talk as a tissue priority conducted to ensure a proper cellular coordination that retails brain damage.

Histomorphological evaluations on the frontal cortex extrapyramidal cell layer following administration of N-Acetyl cysteine in aluminum induced neurodegeneration rat model

“…Aluminum caused extensive expression of astrocytes (gliosis) a condition seen in neurodegenerative conditions such as AD and PD (Raza et al 2014;Sharhripour et al, 2014) in Aluminum treated (Fig.5B) This is attributed to a sustained inflammatory response a crucial fact for the progression of neuron loss in AD (Wang et al 2015), this is term neuro-inflammation characterized by specialized response by activated glial cells (reactive gliosis) an oxidative stress mechanism (McGeer and McGeer 2008;Miller et al 2009). According to Deepmala et al (2015) and Batlle et al (2015) astrocytes are active during neuroinflammation to help neuron repair, support it during injury or toxic assault and restore cerebral homeostasis. However, N-acetylcysteine (NAC) in vivo treatment due to glutathione synthesis, feds glutathione into the neuron milieu thereby regulating redox activating mechanism leading to a reduction in astrocytes expression seen in Fig.…”

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

“…In addition, chronically activated microglia may become increasingly dysfunctional and may directly participate in the development of secondary tissue injury [143]. In contrast, M2 neurorestorative microglia activity includes the production of high levels of anti-inflammatory cytokines like IL-4, IL-10, neurotrophic factors, and proteins such as insulin-like growth factor (IGF)-1, arginase-1 and Ym-1 [144][145][146].…”

“…Rather, microglia become reactive through expression changes in a wide range of genes that mediate the acquisition of new cell functions. This means that, at each moment, the balance of secreted molecules from the 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 F o r R e v i e w O n l y microenvironment determines a spectrum of microglial phenotypes that also vary with the time and intensity of neuron damage [112,145]. However these phenotypes are classified, microglia respond with a large diversity of signals, some of them detrimental and others restorative, which modulate neuroinflammation and thus interfere with ALS progression (Figure 3).…”

Diazoxide enhances excitotoxicity-induced neurogenesis and attenuates neurodegeneration in the rat non-neurogenic hippocampus

“…Half of the animals (6 rats in each group) were used for biochemical studies and the other half were used for histological investigations (Figure 1). The Dzx and NMDA doses were chosen according to previous studies (Virgili et al, 2011;Rodríguez et al, 2013;Batlle et al, 2015).…”

“…The selected Dzx dose did not affect glycemia in rats ( Figure 2A). As they were used at low concentrations, the anesthetics did not interfere with the function of the NMDA receptors (Batlle et al, 2015). 7…”