Adenosine A1 receptor antagonist mitigates deleterious effects of sleep deprivation on adult neurogenesis and spatial reference memory in rats

Chauhan, Garima; Ray, Koushik; Sahu, Shilpi; Roy, Koustav; Jain, Vishal; Wadhwa, Meetu; Panjwani, Usha; Kishore, Krishna; Singh, Shashi Bala

doi:10.1016/j.neuroscience.2016.09.007

Cited by 28 publications

(13 citation statements)

References 60 publications

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“…Spatial memory is a navigational memory depending on the spatial orientation and generally tested using MWM test procedure. The environmental conditions (temperature, humidity, light, and sound) were properly maintained, and the test was performed as per the protocol of Chauhan et al [ 34 ]. The test apparatus comprised of a black painted circular pool (210 cm diameter and 53 cm height), and a transparent platform.…”

Section: Methodsmentioning

confidence: 99%

RETRACTED ARTICLE: Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation

Wadhwa

Prabhakar

Ray

et al. 2017

J Neuroinflammation

187

159

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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.

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Section: Methodsmentioning

confidence: 99%

RETRACTED ARTICLE: Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation

Wadhwa

Prabhakar

Ray

et al. 2017

J Neuroinflammation

187

159

View full text Add to dashboard Cite

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“…Even though the molecular mechanisms underlying the effects of sleep loss are largely unknown, some molecular players have been identified. For example, SD decreases levels of brain-derived neuro-trophic factor (BDNF), a molecule essential for memory retrieval and long-term potentiation, in the hippocampus, and importantly, specifically in the DG (Chauhan et al, 2016; Guzman-Marin et al, 2006; Zagaar et al, 2016). In this same special issue Delorme et al show that ARC, a protein critical for synaptic plasticity like BDNF, is also reduced in the dentate gyrus after 3 h of SD (Delorme et al, in press).…”

Section: Discussionmentioning

confidence: 99%

A brief period of sleep deprivation causes spine loss in the dentate gyrus of mice

Raven

Meerlo

Zee

et al. 2019

Neurobiology of Learning and Memory

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Sleep and sleep loss have a profound impact on hippocampal function, leading to memory impairments. Modifications in the strength of synaptic connections directly influences neuronal communication, which is vital for normal brain function, as well as the processing and storage of information. In a recently published study, we found that as little as five hours of sleep deprivation impaired hippocampus-dependent memory consolidation, which was accompanied by a reduction in dendritic spine numbers in hippocampal area CA1. Surprisingly, loss of sleep did not alter the spine density of CA3 neurons. Although sleep deprivation has been reported to affect the function of the dentate gyrus, it is unclear whether a brief period of sleep deprivation impacts spine density in this region. Here, we investigated the impact of a brief period of sleep deprivation on dendritic structure in the dentate gyrus of the dorsal hippocampus. We found that five hours of sleep loss reduces spine density in the dentate gyrus with a prominent effect on branched spines. Interestingly, the inferior blade of the dentate gyrus seems to be more vulnerable in terms of spine loss than the superior blade. This decrease in spine density predominantly in the inferior blade of the dentate gyrus may contribute to the memory deficits observed after sleep loss, as structural reorganization of synaptic networks in this subregion is fundamental for cognitive processes.

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“…Briefly, the male Sprague-Dawley rats were sleep deprived for 48 h in the automated SD apparatus according to the well-established SD protocol of our lab (Wadhwa et al, 2015 ; Chauhan et al, 2016 ). The exposure paradigm made the rats awake on providing the SD stimulus such as sound, light, and vibration.…”

Section: Methodsmentioning

confidence: 99%

Caffeine and Modafinil Ameliorate the Neuroinflammation and Anxious Behavior in Rats during Sleep Deprivation by Inhibiting the Microglia Activation

Wadhwa

Chauhan

Roy

et al. 2018

Front. Cell. Neurosci.

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Background: Sleep deprivation (SD) plagues modern society due to the professional demands. It prevails in patients with mood and neuroinflammatory disorders. Although growing evidence suggests the improvement in the cognitive performance by psychostimulants during sleep-deprived conditions, the impending involved mechanism is rarely studied. Thus, we hypothesized that mood and inflammatory changes might be due to the glial cells activation induced modulation of the inflammatory cytokines during SD, which could be improved by administering psychostimulants. The present study evaluated the role of caffeine/modafinil on SD-induced behavioral and inflammatory consequences.Methods: Adult male Sprague-Dawley rats were sleep deprived for 48 h using automated SD apparatus. Caffeine (60 mg/kg/day) or modafinil (100 mg/kg/day) were administered orally to rats once every day during SD. Rats were subjected to anxious and depressive behavioral evaluation after SD. Subsequently, blood and brain were collected for biochemical, immunohistochemical and molecular studies.Results: Sleep deprived rats presented an increased number of entries and time spent in closed arms in elevated plus maze test and decreased total distance traveled in the open field (OF) test. Caffeine/modafinil treatment significantly improved these anxious consequences. However, we did not observe substantial changes in immobility and anhedonia in sleep-deprived rats. Caffeine/modafinil significantly down-regulated the pro- and up-regulated the anti-inflammatory cytokine mRNA and protein expression in the hippocampus during SD. Similar outcomes were observed in blood plasma cytokine levels. Caffeine/modafinil treatment significantly decreased the microglial immunoreactivity in DG, CA1 and CA3 regions of the hippocampus during SD, however, no significant increase in immunoreactivity of astrocytes was observed. Sholl analysis signified the improvement in the morphological alterations of astrocytes and microglia after caffeine/modafinil administration during SD. Stereological analysis demonstrated a significant improvement in the number of ionized calcium binding adapter molecule I (Iba-1) positive cells (different states) in different regions of the hippocampus after caffeine or modafinil treatment during SD without showing any significant change in total microglial cell number. Eventually, the correlation analysis displayed a positive relationship between anxiety, pro-inflammatory cytokines and activated microglial cell count during SD.Conclusion: The present study suggests the role of caffeine or modafinil in the amelioration of SD-induced inflammatory response and anxious behavior in rats.Highlights- SD induced mood alterations in rats.- Glial cells activated in association with the changes in the inflammatory cytokines.- Caffeine or modafinil improved the mood and restored inflammatory changes during SD.- SD-induced anxious behavior correlated with the inflammatory consequences.

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Adenosine A1 receptor antagonist mitigates deleterious effects of sleep deprivation on adult neurogenesis and spatial reference memory in rats

Cited by 28 publications

References 60 publications

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

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

A brief period of sleep deprivation causes spine loss in the dentate gyrus of mice

Caffeine and Modafinil Ameliorate the Neuroinflammation and Anxious Behavior in Rats during Sleep Deprivation by Inhibiting the Microglia Activation

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