PMID- 29141671 OWN - NLM STAT- MEDLINE DCOM- 20180724 LR - 20211204 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 14 IP - 1 DP - 2017 Nov 15 TI - Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation. PG - 222 LID - 10.1186/s12974-017-0998-z [doi] LID - 222 AB - BACKGROUND: Sleep 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. METHODS: Male 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. RESULTS: Minocycline 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. CONCLUSION: The 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. Microglial activation is involved in SD-induced changes in inflammatory molecules, neurogenesis, and spatial memory. FAU - Wadhwa, Meetu AU - Wadhwa M AD - Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Lucknow Road, Timarpur, Delhi, India. FAU - Prabhakar, Amit AU - Prabhakar A AD - Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Lucknow Road, Timarpur, Delhi, India. FAU - Ray, Koushik AU - Ray K AD - Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Lucknow Road, Timarpur, Delhi, India. FAU - Roy, Koustav AU - Roy K AD - Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Lucknow Road, Timarpur, Delhi, India. FAU - Kumari, Punita AU - Kumari P AD - Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Lucknow Road, Timarpur, Delhi, India. FAU - Jha, Prabhash Kumar AU - Jha PK AD - Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Lucknow Road, Timarpur, Delhi, India. FAU - Kishore, Krishna AU - Kishore K AD - Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Lucknow Road, Timarpur, Delhi, India. FAU - Kumar, Sanjeev AU - Kumar S AD - Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Lucknow Road, Timarpur, Delhi, India. FAU - Panjwani, Usha AU - Panjwani U AD - Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Lucknow Road, Timarpur, Delhi, India. neurophysiolab.dipas@gmail.com. AD - Neurophysiology Division, Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), Lucknow Road, Timarpur, Delhi, -110 054, India. neurophysiolab.dipas@gmail.com. LA - eng PT - Journal Article DEP - 20171115 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 SB - IM MH - Animals MH - Cognition Disorders/immunology MH - Doublecortin Protein MH - Hippocampus/*immunology/pathology MH - Male MH - Maze Learning MH - Microglia/immunology/*pathology MH - Neurogenesis/*immunology MH - Rats MH - Rats, Sprague-Dawley MH - Sleep Deprivation/*complications/immunology MH - Spatial Memory/*physiology PMC - PMC5688670 OTO - NOTNLM OT - Cytokines OT - Microglia OT - Minocycline OT - Neurogenesis OT - Neuroinflammation OT - Sleep deprivation OT - Spatial memory COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Human volunteers did not participate in the study. Animal experiments were conducted after the approval from the Animal Ethics Committee. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/11/17 06:00 MHDA- 2018/07/25 06:00 PMCR- 2017/11/15 CRDT- 2017/11/17 06:00 PHST- 2017/07/21 00:00 [received] PHST- 2017/11/08 00:00 [accepted] PHST- 2017/11/17 06:00 [entrez] PHST- 2017/11/17 06:00 [pubmed] PHST- 2018/07/25 06:00 [medline] PHST- 2017/11/15 00:00 [pmc-release] AID - 10.1186/s12974-017-0998-z [pii] AID - 998 [pii] AID - 10.1186/s12974-017-0998-z [doi] PST - epublish SO - J Neuroinflammation. 2017 Nov 15;14(1):222. doi: 10.1186/s12974-017-0998-z.