Lithium chloride administration prevents spatial learning and memory impairment in repeated cerebral ischemia-reperfusion mice by depressing apoptosis and increasing BDNF expression in hippocampus

Fan, Mingyue; Jin, Wei; Zhao, Haifeng; Xiao, Yining; Jia, Yanqiu; Yin, You; Jiang, Xin; Xu, Jing; Meng, Nan; Lv, Peiyuan

doi:10.1016/j.bbr.2015.05.047

Cited by 35 publications

(25 citation statements)

References 40 publications

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“…An increase in caspase-3 protein expression was also observed in the voluntary exercise group. These findings are in accordance with numerous studies that have suggested that BDNF represses cell apoptosis in ischemia (Yao et al, 2012;Fan et al, 2015;Asadi et al, 2018) and it is surmised that the underlying mechanism of suppressed apoptosis might be related to BDNF. Furthermore, the voluntary running model is implemented in rat home cages, and this method may involve the effect of enriched environment.…”

Section: Discussionsupporting

confidence: 92%

Voluntary exercise promotes neurotrophic factor and suppresses apoptosis in hippocampal ischemia

2019

J. Integr. Neurosci.

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J o u r n a l o f I n t e g r a t i v e N e u r o s c i e n c eThis is an open access article under the CC BY-NC 4.0 license (https://creativecommons.org/licenses/by-nc/4.0/) Previous studies have demonstrated that exercise facilitates recovery from ischemia. However, the mechanisms need to be further elucidated. The current investigation was designed to study the effect of voluntary exercise on cerebral ischemia and discuss possible mechanisms usingmiddle cerebral artery occlusion model. Rats were randomly allocated to three groups: control, middle cerebral artery occlusion, and middle cerebral artery occlusion plus exercise. The middle cerebral artery occlusion plus exercise group was preconditioned by three weeks of voluntary wheel running prior to surgery. The accelerated rotarod test was employed to evaluate motor performance. Infarct volumes were analyzed to detect the neuroprotective effect of voluntary exercise. Brain-derived neurotrophic factor, Bax, Bcl-2, and caspase-3 protein expressions were measured by Western blot. Behavior evaluation showed the middle cerebral artery occlusion plus exercise group achieved significantly longer time on a rotarod than the unexercised group. Additionally, voluntary exercise reduced cerebral infarction and increased brain derived neurotrophic factor expression. Exercise downregulated the apoptotic Bax/Bcl-2 ratio and caspase-3 protein expression. Results indicate that voluntary wheel running promote hippocampal brain derived neurotrophic factor and inhibit cell apoptosis in ischemia-induced impairment. KeywordsHippocampal ischemia; voluntary exercise; brain-derived neurotrophic factor; apoptosis; rodent Abbreviations BDNF Brain-derived neurotrophic factor CCA Common carotid artery ECA External carotid artery ICA Internal carotid artery MCA Middle cerebral artery MCAO Middle cerebral artery occlusion TTC 2,3,5-Triphenyl-tetrazolium chloride solution

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Section: Discussionsupporting

confidence: 92%

Voluntary exercise promotes neurotrophic factor and suppresses apoptosis in hippocampal ischemia

2019

J. Integr. Neurosci.

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“…It is a known target of lithium [37], a medication that could be used for memory disorders improvement and prevention of AD, particularly in individuals with mood disorders earlier in life. Lithium is known to have anti-apoptotic roles [38,39], so it is possible that it may prevent the neuronal loss of viability that is a precursor and part of AD, and which in turn triggers and is accentuated by the scar-like deposition of MAPT and APP.…”

Section: Pathophysiological Insightsmentioning

confidence: 99%

Blood biomarkers for memory: toward early detection of risk for Alzheimer disease, pharmacogenomics, and repurposed drugs

et al. 2019

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Short-term memory dysfunction is a key early feature of Alzheimer's disease (AD). Psychiatric patients may be at higher risk for memory dysfunction and subsequent AD due to the negative effects of stress and depression on the brain. We carried out longitudinal within-subject studies in male and female psychiatric patients to discover blood gene expression biomarkers that track short term memory as measured by the retention measure in the Hopkins Verbal Learning Test. These biomarkers were subsequently prioritized with a convergent functional genomics approach using previous evidence in the field implicating them in AD. The top candidate biomarkers were then tested in an independent cohort for ability to predict state short-term memory, and trait future positive neuropsychological testing for cognitive impairment. The best overall evidence was for a series of new, as well as some previously known genes, which are now newly shown to have functional evidence in humans as blood biomarkers: RAB7A, NPC2, TGFB1, GAP43, ARSB, PER1, GUSB, and MAPT. Additional top blood biomarkers include GSK3B, PTGS2, APOE, BACE1, PSEN1, and TREM2, well known genes implicated in AD by previous brain and genetic studies, in humans and animal models, which serve as reassuring de facto positive controls for our whole-genome gene expression discovery approach. Biological pathway analyses implicate LXR/RXR activation, neuroinflammation, atherosclerosis signaling, and amyloid processing. Co-directionality of expression data provide new mechanistic insights that are consistent with a compensatory/scarring scenario for brain pathological changes. A majority of top biomarkers also have evidence for involvement in other psychiatric disorders, particularly stress, providing a molecular basis for clinical co-morbidity and for stress as an early precipitant/risk factor. Some of them are modulated by existing drugs, such as antidepressants, lithium and omega-3 fatty acids. Other drug and nutraceutical leads were identified through bioinformatic drug repurposing analyses (such as pioglitazone, levonorgestrel, salsolidine, ginkgolide A, and icariin). Our work contributes to the overall pathophysiological understanding of memory disorders and AD. It also opens new avenues for precision medicine-diagnostics (assement of risk) as well as early treatment (pharmacogenomically informed, personalized, and preventive).

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“…Additionally, low brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus may contribute to deteriorative apoptosis of a subpopulation of hippocampal neurons, decreasing neuronal survival as well as impairing spatial learning and memory after cerebral ischemia (Fan et al, 2015; Soares et al, 2017). Despite advances in revealing the pathophysiology of cerebral ischemia at the molecular, cellular, and animal levels, the challenge of finding therapeutic options remains striking due to the serious side effects of drugs accompanied by a very short therapeutic window (≤6 h post-stroke) as well as secondary damage from ischemia and reperfusion injury (Donnan et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Danshen-Chuanxiong-Honghua Ameliorates Cerebral Impairment and Improves Spatial Cognitive Deficits after Transient Focal Ischemia and Identification of Active Compounds

et al. 2017

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Previously, we only apply a traditional Chinese medicine (TCM) Danshen-Chuanxiong-Honghua (DCH) for cardioprotection via anti-inflammation in rats of acute myocardial infarction by occluding coronary artery. Presently, we select not only DCH but also its main absorbed compound ferulic acid (FA) for cerebra protection via similar action of mechanism above in animals of the transient middle cerebral artery occlusion (tMCAO). We investigated whether oral administration of DCH and FA could ameliorate MCAO-induced brain lesions in animals. By using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we analyzed four compounds, including tanshinol, salvianolic acid B, hydroxysafflor yellow A and especially FA as the putative active components of DCH extract in the plasma, cerebrospinal fluid and injured hippocampus of rats with MCAO. In our study, it was assumed that FA played a similar neuroprotective role to DCH. We found that oral pretreatment with DCH (10 or 20 g/kg) and FA (100 mg/kg) improved neurological function and alleviated the infarct volume as well as brain edema in a dose-dependent manner. These changes were accompanied by improved ischemia-induced apoptosis and decreased the inflammatory response. Additionally, chronic treatment with DCH reversed MCAO-induced spatial cognitive deficits in a manner associated with enhanced neurogenesis and increased the expression of brain-derived neurotrophic factor in lesions of the hippocampus. These findings suggest that DCH has the ability to recover cognitive impairment and offer neuroprotection against cerebral ischemic injury via inhibiting microenvironmental inflammation and triggering of neurogenesis in the hippocampus. FA could be one of the potential active compounds.

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Lithium chloride administration prevents spatial learning and memory impairment in repeated cerebral ischemia-reperfusion mice by depressing apoptosis and increasing BDNF expression in hippocampus

Cited by 35 publications

References 40 publications

Voluntary exercise promotes neurotrophic factor and suppresses apoptosis in hippocampal ischemia

Voluntary exercise promotes neurotrophic factor and suppresses apoptosis in hippocampal ischemia

Blood biomarkers for memory: toward early detection of risk for Alzheimer disease, pharmacogenomics, and repurposed drugs

Danshen-Chuanxiong-Honghua Ameliorates Cerebral Impairment and Improves Spatial Cognitive Deficits after Transient Focal Ischemia and Identification of Active Compounds

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