Complement activation sustains neuroinflammation and deteriorates adult neurogenesis and spatial memory impairment in rat hippocampus following sleep deprivation

Wadhwa, Meetu; Prabhakar, Amit; Anand, Jag Pravesh; Ray, Koushik; Prasad, Dipti; Kumar, Bhuvnesh; Panjwani, Usha

doi:10.1016/j.bbi.2019.08.004

Cited by 56 publications

(25 citation statements)

References 64 publications

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“…Studies have shown that the complement pathway is activated during wakefulness [273,274]. Measuring the immunoglobulins and complement levels in serum can help us to assess the function of the immune system and study the impairment and restorative processes that happen during wakefulness and sleep and the consequences due to sleep loss.…”

Section: Complementsmentioning

confidence: 99%

The effect of insomnia on development of Alzheimer’s disease

Sadeghmousavi

Eskian

Rahmani

et al. 2020

J Neuroinflammation

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Alzheimer’s disease (AD) is the most common type of dementia and a neurodegenerative disorder characterized by memory deficits especially forgetting recent information, recall ability impairment, and loss of time tracking, problem-solving, language, and recognition difficulties. AD is also a globally important health issue but despite all scientific efforts, the treatment of AD is still a challenge. Sleep has important roles in learning and memory consolidation. Studies have shown that sleep deprivation (SD) and insomnia are associated with the pathogenesis of Alzheimer’s disease and may have an impact on the symptoms and development. Thus, sleep disorders have decisive effects on AD; this association deserves more attention in research, diagnostics, and treatment, and knowing this relation also can help to prevent AD through screening and proper management of sleep disorders. This study aimed to show the potential role of SD and insomnia in the pathogenesis and progression of AD.

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Section: Complementsmentioning

confidence: 99%

The effect of insomnia on development of Alzheimer’s disease

Sadeghmousavi

Eskian

Rahmani

et al. 2020

J Neuroinflammation

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“…Using a mouse model devoid of C5 complement signaling, rhythmic HPSC recruitment could be entirely blocked, implicating the importance of circadian complement pathway activation in immune surveillance (Massberg et al, 2007;Janowska-Wieczorek et al, 2012;Ratajczak et al, 2012;Budkowska et al, 2018). While this study implicates rhythmic complement activation in the context of circulating HPSCs, other studies have shown a sleep-dependent increases in C3, C4, C3a, C5a, and complement factor I (CFI) ultimately resulting in dysregulated cytokines production (Reis et al, 2011;Manzar et al, 2016;Horvath et al, 2018;Wadhwa et al, 2019). Using the Pittsburgh Sleep Quality Index (PSQI) in a relatively small number of male university students, Manzar et al demonstrated that poor sleep quality correlates with decreased proinflammatory C3 and C4 in the serum and increased levels of anti-inflammatory CFI during early bedtime and daytime (Manzar et al, 2015), suggesting that regular sleep patterns may be important for the normal cycling of complement factors.…”

Section: Co-regulatory Roles Of Complement and Sleep On Immunosurveilmentioning

confidence: 71%

“…C3a and C5a peptides are potent cytokines that signal through their respective receptors, C3aR and C5aR1 on myeloid and non-myeloid cells, thereby increasing inflammation and chemotaxis (Markiewski and Lambris, 2007 ; Dunkelberger and Song, 2010 ; Holers, 2014 ). Although the alternate complement pathway acts as a surveillance mechanism in healthy tissues, dysregulation of the alternate complement pathway can result in chronic inflammatory conditions including, but not limited to, inflammatory bowel diseases (IBD), cardiac inflammation, autoimmune diseases, and glomerulonephropathies (Aiyaz et al, 2012 ; Carter, 2012 ; Fearn and Sheerin, 2015 ; Wadhwa et al, 2019 ). These conditions usually arise in part from uncontrolled production of complement anaphylatoxins of the alternate complement pathway.…”

Section: Introductionmentioning

confidence: 99%

Circadian Clock and Complement Immune System—Complementary Control of Physiology and Pathology?

Shivshankar

Fekry

Eckel‐Mahan

et al. 2020

Front. Cell. Infect. Microbiol.

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Mammalian species contain an internal circadian (i.e., 24-h) clock that is synchronized to the day and night cycles. Large epidemiological studies, which are supported by carefully controlled studies in numerous species, support the idea that chronic disruption of our circadian cycles results in a number of health issues, including obesity and diabetes, defective immune response, and cancer. Here we focus specifically on the role of the complement immune system and its relationship to the internal circadian clock system. While still an incompletely understood area, there is evidence that dysregulated proinflammatory cytokines, complement factors, and oxidative stress can be induced by circadian disruption and that these may feed back into the oscillator at the level of circadian gene regulation. Such a feedback cycle may contribute to impaired host immune response against pathogenic insults. The complement immune system including its activated anaphylatoxins, C3a and C5a, not only facilitate innate and adaptive immune response in chemotaxis and phagocytosis, but they can also amplify chronic inflammation in the host organism. Consequent development of autoimmune disorders, and metabolic diseases associated with additional environmental insults that activate complement can in severe cases, lead to accelerated tissue dysfunction, fibrosis, and ultimately organ failure. Because several promising complement-targeted therapeutics to block uncontrolled complement activation and treat autoimmune diseases are in various phases of clinical trials, understanding fully the circadian properties of the complement system, and the reciprocal regulation by these two systems could greatly improve patient treatment in the long term.

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“…In particular, sleep disorders can cause many changes in endogenous regulatory factors, which in turn can cause hyperalgesia. For example, insufficient sleep leads to increased migration of B cells into the brain compartment [24], activation of complement [47], and increased levels of IL-1 [55], thus leading to the onset and aggravation of neuroinflammation, a key factors underlying pain. In addition, stress caused by sleep disorders can cause dysfunction of the HPA axis, causing cortisol dysfunction to trigger, exacerbate, or prolong pain, impair healing, and contribute to chronic disability [20].…”

Section: Discussionmentioning

confidence: 99%

Sleep deprivation of rats increases postsurgical expression and activity of L-type calcium channel in the dorsal root ganglion and slows recovery from postsurgical pain

Zhu

et al. 2019

acta neuropathol commun

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Perioperative sleep disturbance is a risk factor for persistent pain after surgery. Clinical studies have shown that patients with insufficient sleep before and after surgery experience more intense and long-lasting postoperative pain. We hypothesize that sleep deprivation alters L-type calcium channels in the dorsal root ganglia (DRG), thus delaying the recovery from post-surgical pain. To verify this hypothesis, and to identify new predictors and therapeutic targets for persistent postoperative pain, we first established a model of postsurgical pain with perioperative sleep deprivation (SD) by administering hind paw plantar incision to sleep deprivation rats. Then we conducted behavioral tests, including tests with von Frey filaments and a laser heat test, to verify sensory pain, measured the expression of L-type calcium channels using western blotting and immunofluorescence of dorsal root ganglia (an important neural target for peripheral nociception), and examined the activity of L-type calcium channels and neuron excitability using electrophysiological measurements. We validated the findings by performing intraperitoneal injections of calcium channel blockers and microinjections of dorsal root ganglion cells with adeno-associated virus. We found that short-term sleep deprivation before and after surgery increased expression and activity of L-type calcium channels in the lumbar dorsal root ganglia, and delayed recovery from postsurgical pain. Blocking these channels reduced impact of sleep deprivation. We conclude that the increased expression and activity of L-type calcium channels is associated with the sleep deprivation-mediated prolongation of postoperative pain. L-type calcium channels are thus a potential target for management of postoperative pain.

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Complement activation sustains neuroinflammation and deteriorates adult neurogenesis and spatial memory impairment in rat hippocampus following sleep deprivation

Cited by 56 publications

References 64 publications

The effect of insomnia on development of Alzheimer’s disease

The effect of insomnia on development of Alzheimer’s disease

Circadian Clock and Complement Immune System—Complementary Control of Physiology and Pathology?

Sleep deprivation of rats increases postsurgical expression and activity of L-type calcium channel in the dorsal root ganglion and slows recovery from postsurgical pain

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