Prophylactic lithium alleviates splenectomy-induced cognitive dysfunction possibly by inhibiting hippocampal TLR4 activation in aged rats

Lu, Shunmei; Gui, Bo; Dong, Huijuan; Zhang, Xiang; Zhang, Susu; Hu, Liu‐Qing; Liu, Hailing; Sun, Jie; Qian, Yian-Ning

doi:10.1016/j.brainresbull.2015.02.008

Cited by 37 publications

(33 citation statements)

References 64 publications

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“…Recently, TLR4 was also identified as a modulator of neurogenesis in the brain during injuries, cerebral ischemia, and cognitive decline [12], and it is recognized to contribute to neuroplasticity [13]. Studies demonstrated that cognitive dysfunction was alleviated possibly by inhibiting hippocampal TLR4 activation in aged rats [14]. Moreover, the improvement of cognitive deficits was accompanied by the attenuation of inflammatory injury and apoptosis via TLR4 activation and its downstream signaling pathways [15,16].…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

et al. 2020

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Toll-like receptor 4 (TLR4) is a crucial receptor in neuroinflammation and apoptotic neuronal death, and increasing evidences indicated that β2-microglobulin (B2M) is thought to be a major contributor to age-related cognitive decline. In present study, we designed to investigate the effects of TLR4 on B2M-induced age-related cognitive decline. Wild-type (WT) C57BL/6, TLR4 knockout (TLR4-KO) mice and hippocampal neurons from the two type mice were respectively divided into two groups: (1) Veh group; (2) B2M-treated group. The behavioral responses of mice were measured using Morris Water Maze. Hippocampal neurogenesis and neuronal damage, inflammatory response, apoptosis, synaptic proteins and neurotrophic factors, and TLR4/MyD88/NF-κB signaling pathway proteins were examined using molecular biological or histopathological methods. The results showed that WT mice received B2M in the DG exhibited age-related cognitive declines, increased TLR4 mRNA expression and high levels of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and apoptotic neuronal death in the hippocampus, which were partially attenuated in TLR4-KO mice. Moreover, in absence of TLR4, B2M treatment improved hippocampus neurogenesis and increased synaptic related proteins. Our cell experiments further demonstrated that deletion of TLR4 could significantly increase synaptic related protein, decrease neuroinflammatory fators, inhibited apoptotic neuronal death, and regulated MyD88/NF-κB signal pathway after B2M treatment. In summary, our results support the TLR4 contributes to B2M-induced age-related cognitive decline due to neuroinflammation and apoptosis through TLR4/MyD88/NF-κB signaling pathway via a modulation of hippocampal neurogenesis and synaptic function. This may provide an important neuroprotective mechanism for improving age-related cognitive decline.

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Section: Introductionmentioning

confidence: 99%

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

et al. 2020

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“…Lithium, an inhibitor of GSK3 β , exhibits neuroprotective effects in various models [ 25 – 27 ]. Therefore, we investigated whether lithium pretreatment can reverse isoflurane-induced learning and memory impairment.…”

Section: Resultsmentioning

confidence: 99%

Isoflurane Is More Deleterious to Developing Brain Than Desflurane: The Role of the Akt/GSK3βSignaling Pathway

Tao

Xue

Luo

et al. 2016

BioMed Research International

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Demand is increasing for safer inhalational anesthetics for use in pediatric anesthesia. In this regard, researchers have debated whether isoflurane is more toxic to the developing brain than desflurane. In the present study, we compared the effects of postnatal exposure to isoflurane with those of desflurane on long-term cognitive performance and investigated the role of the Akt/GSK3β signaling pathway. Postnatal day 6 (P6) mice were exposed to either isoflurane or desflurane, after which the phosphorylation levels of Akt/GSK3β and learning and memory were assessed at P8 or P31. The phosphorylation levels of Akt/GSK3β and learning and memory were examined after intervention with lithium. We found that isoflurane, but not desflurane, impaired spatial learning and memory at P31. Accompanied by behavioral change, only isoflurane decreased p-Akt (ser473) and p-GSK3β (ser9) expressions, which led to GSK3β overactivation. Lithium prevented GSK3β overactivation and alleviated isoflurane-induced cognitive deficits. These results suggest that isoflurane is more likely to induce developmental neurotoxicity than desflurane in context of multiple exposures and that the Akt/GSK3β signaling pathway partly participates in this process. GSK3β inhibition might be an effective way to protect against developmental neurotoxicity.

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“…The Maze's group reported this model initially in 2010 (Cibelli et al, 2010). Splenectomy (Lu et al, 2015), partial hepatectomy (Tian et al, 2017), exploratory laparotomy (Qiu et al, 2016), and right common carotid artery occlude (Sanches et al, 2013) were also utilized as POCD model. Maze group demonstrated that tibial fracture fixation impaired the performance of mice in the fear conditioning test (Cibelli et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Central cholinergic system mediates working memory deficit induced by anesthesia/surgery in adult mice

et al. 2018

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BackgroundPostoperative cognitive dysfunction (POCD) is consistently associated with increased morbidity and mortality, which has become a major concern of patients and caregivers. Although POCD occurs mainly in aged patients, it happens at any age. Previous studies demonstrated that anesthesia/surgery had no effects on reference memory of adult mice. However, whether it impairs working memory remains unclear. Working memory deficit would result in many deficits of executive function. We hypothesized that anesthesia/surgery impaired the working memory of adult mice and the central cholinergic system was involved.MethodTibial fracture internal fixation under the anesthesia of isoflurane was performed in two‐month‐old C57BL/6 mice. Two days later, the spatial reference memory and working memory were measured by a Morris Water Maze (MWM). Donepezil, an inhibitor of acetylcholinesterase (AChE), was administered in another cohort mice for 4 weeks. Then, the working memory was measured by MWM 2 days after anesthesia/surgery. Western blot was used to detect the protein levels of acetylcholine transferase (ChAT), AChE, vesicular acetylcholine transporter (VAChT), and choline transporter (ChT) in the prefrontal cortex (PFC).ResultsWe found that anesthesia/surgery had no effects on the reference memory, but it impaired the working memory in adult mice. Meanwhile, we also found that the protein level of ChAT in PFC decreased significantly compared with that in control group. Donepezil pretreatment prevented working memory impairment and the decrease of the protein levels of ChAT induced by anesthesia/surgery.ConclusionThese results suggest that anesthesia/surgery leads to working memory deficits in adult mice and central cholinergic system impairment is involved.

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Prophylactic lithium alleviates splenectomy-induced cognitive dysfunction possibly by inhibiting hippocampal TLR4 activation in aged rats

Cited by 37 publications

References 64 publications

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

Toll-like receptor 4 deficiency ameliorates β2-microglobulin induced age-related cognition decline due to neuroinflammation in mice

Isoflurane Is More Deleterious to Developing Brain Than Desflurane: The Role of the Akt/GSK3βSignaling Pathway

Central cholinergic system mediates working memory deficit induced by anesthesia/surgery in adult mice

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