RETRACTED ARTICLE: Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation

Abstract

BackgroundSleep deprivation (SD) leads to cognitive impairment. Neuroinflammation could be a significant contributing factor in the same. An increase in regional brain pro-inflammatory cytokines induces cognitive deficits, however, the magnitude of the effect under SD is not apparent. It is plausible that microglia activation could be involved in the SD-induced cognitive impairment by modulation of neuronal cell proliferation, differentiation, and brain-derived neuronal factor (BDNF) level. The present study aimed to evaluate the possible beneficial effect of minocycline in amelioration of spatial memory decline during SD by its anti-inflammatory and neuroprotective actions. We scrutinized the effect of minocycline on the inflammatory cytokine levels associated with glial cells (microglia and astrocytes) activity and neurogenesis markers crucial for behavioral functions during SD.MethodsMale Sprague-Dawley rats weighing 230–250 g were sleep deprived for 48 h using automated cage shaking apparatus. The spatial memory was tested using MWM apparatus immediately after completion of SD with and without minocycline. The animals were euthanized, blood was collected, and brain was extracted for neuroinflammation and neurogenesis studies. The set of experiments were also conducted with use of temozolomide, a neurogenesis blocker.ResultsMinocycline treatment increased the body weight, food intake, and spatial memory performance which declined during SD. It reduced the pro-inflammatory and increased the anti-inflammatory cytokine levels in hippocampus and plasma and inhibited the reactive gliosis in the hippocampus evidenced by improved cell count, morphology, and immunoreactivity. Additionally, minocycline administration promoted neurogenesis at different stages: proliferation (BrdU, Ki-67), differentiation (DCX) cells and growth factor (BDNF). However, no significant change was observed in maturation (NeuN) during SD. In addition, molecules related to behavior, inflammation, and neurogenesis were shown to be more affected after temozolomide administration during SD, and changes were restored with minocycline treatment. We observed a significant correlation of neurogenesis with microglial activation, cytokine levels, and spatial memory during SD.ConclusionThe present study demonstrated that the SD-induced decline in spatial memory, neuronal cells proliferation, differentiation, and BDNF level could be attributed to upregulation of neuroinflammatory molecules, and minocycline may be an effective intervention to counteract these changes.Graphical abstractMicroglial activation is involved in SD-induced changes in inflammatory molecules, neurogenesis, and spatial memory. Electronic supplementary materialThe online version of this article (10.1186/s12974-017-0998-z) contains supplementary material, which is available to authorized users.

Hippocampal microglial activation triggers a neurotoxic-specific astrocyte response and mediates etomidate-induced long-term synaptic inhibition

“…For example, cytokines (especially HMGB1, NFκB, and TNFα [30]) secreted from circulating or fixed mononuclear cells regulated microglial feedback reactions [31], upregulating MCP-1 expression and inflammatory cascade signaling pathways and triggering neuroinflammation in the hippocampus [32]. In addition, microglial elimination or inhibition suppressed hippocampal inflammatory responses and reduced the levels of cytokines such as IL-6, IL-1β, and TNFα following anesthesia and other pathological conditions [17,33,34]. Moreover, the level of inositol 1,4,5-triphosphate type 2 receptor-dependent calcium was reduced in astrocytes, even after a sedative dose of anesthetic [35], and long-term inhibition of astrocytes is consistent with synaptic suppression and cognitive deficiencies [24].…”

Treatment with Minocycline Suppresses Microglia Activation and Reverses Neural Stem Cells Loss after Simulated Microgravity

“…For example, microglia produce inflammatory cytokines to reduce the survival of newborn neurons after focal cerebral ischemia [26]. Inhibiting microglia activation improves spatial memory and adult neurogenesis in the rat hippocampus during 48 h of sleep deprivation [27]. Next, we investigated the function of microglia in neurogenesis after exposure to microgravity and found that the microglia were activated and the number of NSCs decreased strikingly in rat hippocampus after 7 d tail suspension.…”

Activation of the α2A adrenoceptor in microglia promotes LPS-induced TNF-α production and cognitive impairment in mice

“…It has been reported that inflammatory factors can affect the function of synaptic connections. In a mouse model of sleep deprivation, an upsurge in inflammatory factors such as TNF-α, IL-1β and IL-6 derived from activated microglia was found in the dentate gyrus and CA2-3 areas of the hippocampus, which was coupled by a significant decline in spatial memory function [38]. IL-1β can reduce the expression of synaptophysin in presynaptic membrane and PSD-95 in postsynaptic of septic rats model, thereby reducing LTP [39,40] through MAPK pathway.…”