Chronic oleoylethanolamide treatment improves spatial cognitive deficits through enhancing hippocampal neurogenesis after transient focal cerebral ischemia

Yang, Lichao; Guo, Hong-Fen; Zhou, Hai-Rong; Suo, Daqin; Li, Wenjun; Zhou, Yu; Zhao, Yun; Yang, Wu; Jin, Xin

doi:10.1016/j.bcp.2015.02.012

Cited by 57 publications

(46 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the PASAT test did not show any improvement, we found a positive effect of PEA treatment in the cognitive function and health in the MSQoL questionnaire. This result is in line with recent preclinical studies, showing that NAEs may exert a beneficial effect following cognitive impairments [45][46][47].…”

Section: Discussionsupporting

confidence: 92%

Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-β1a and Circulating Proinflammatory Cytokines in Relapsing–Remitting Multiple Sclerosis

et al. 2016

View full text Add to dashboard Cite

Palmitoylethanolamide (PEA) is an endogenous lipid mediator known to reduce pain and inflammation. However, only limited clinical studies have evaluated the effects of PEA in neuroinflammatory and neurodegenerative diseases. Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disease of the central nervous system. Although subcutaneous administration of interferon (IFN)-β1a is approved as first-line therapy for the treatment of relapsing-remitting MS (RR-MS), its commonly reported adverse events (AEs) such as pain, myalgia, and erythema at the injection site, deeply affect the quality of life (QoL) of patients with MS. In this randomized, double-blind, placebocontrolled study, we tested the effect of ultramicronized PEA (um-PEA) added to IFN-β1a in the treatment of clinically defined RR-MS. The primary objectives were to estimate whether, with um-PEA treatment, patients with MS perceived an improvement in pain and a decrease of the erythema width at the IFN-β1a injection site in addition to an improvement in their QoL. The secondary objectives were to evaluate the effects of um-PEA on circulating interferon-γ, tumor necrosis factor-α, and interleukin-17 serum levels, N-acylethanolamine plasma levels, Expanded Disability Status Scale (EDSS) progression, and safety and tolerability after 1 year of treatment. Patients with MS receiving um-PEA perceived an improvement in pain sensation without a reduction of the erythema at the injection site. A significant improvement in QoL was observed. No significant difference was reported in EDSS score, and um-PEA was well tolerated. We found a significant increase of palmitoylethanolamide, anandamide and oleoylethanolamide plasma levels, and a significant reduction of interferon-γ, tumor necrosis factor-α, and interleukin-17 serum profile compared with the placebo group. Our results suggest that um-PEA may be considered as an appropriate add-on therapy for the treatment of IFN-β1a-related adverse effects in RR-MS.

show abstract

Section: Discussionsupporting

confidence: 92%

Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-β1a and Circulating Proinflammatory Cytokines in Relapsing–Remitting Multiple Sclerosis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Neurogenesis and neuroregeneration promote functional recovery after ischemic stroke, which causes local hypoxia [31,43,44]. Here, we showed that after hypoxia, PFK-1 knockdown increased, and PFK-1 overexpression inhibited neurogenesis from NSCs, suggesting an important role for PFK-1 in the regulation of neurogenesis under pathological conditions.…”

Section: Discussionmentioning

confidence: 84%

“…Several lines of evidence have shown that increased neurogenesis after brain injury improves cognitive outcome and promotes repair [43,44]. Thus, if enhanced, neurogenesis may offer a better treatment alternative, and is poised to make another leap forward.…”

Section: Discussionmentioning

confidence: 98%

Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells

et al. 2016

View full text Add to dashboard Cite

Phosphofructokinase-1 (PFK-1), a major regulatory glycolytic enzyme, has been implicated in the functions of astrocytes and neurons. Here, we report that PFK-1 negatively regulates neurogenesis from neural stem cells (NSCs) by targeting pro-neural transcriptional factors. Using in vitro assays, we found that PFK-1 knockdown enhanced, and PFK-1 overexpression inhibited the neuronal differentiation of NSCs, which was consistent with the findings from NSCs subjected to 5 h of hypoxia. Meanwhile, the neurogenesis induced by PFK-1 knockdown was attributed to the increased proliferation of neural progenitors and the commitment of NSCs to the neuronal lineage. Similarly, in vivo knockdown of PFK-1 also increased neurogenesis in the dentate gyrus of the hippocampus. Finally, we demonstrated that the neurogenesis mediated by PFK-1 was likely achieved by targeting mammalian achaete-scute homologue-1 (Mash 1), neuronal differentiation factor (NeuroD), and sex-determining region Y (SRY)-related HMG box 2 (Sox2). All together, our results reveal PFK-1 as an important regulator of neurogenesis.

show abstract

“…The impairment of spatial memory tasks is generally considered to be induced by ischemia and reperfusion insults in the hippocampus (Yang et al, 2015a), and we thereby used the MWM to survey cognitive deficits. Interestingly, our results demonstrated that DCH-treatment for 4 weeks significantly reduced the escape latency during the training compared with that of vehicle treatment, suggesting that DCH decreased the ischemia-induced spatial learning deficits.…”

Section: Discussionmentioning

confidence: 99%

“…Every fifth coronal brain section throughout the hippocampus, which was 400 μm apart, was selected for BrdU immunofluorescence staining as previously described (Yang et al, 2015a). In brief, sections were pretreated with 2 N HCl at 37°C for 60 min followed by rinses in 0.1 M borate buffer for 10 min (pH 8.5).…”

Section: Methodsmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Chronic oleoylethanolamide treatment improves spatial cognitive deficits through enhancing hippocampal neurogenesis after transient focal cerebral ischemia

Cited by 57 publications

References 56 publications

Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-β1a and Circulating Proinflammatory Cytokines in Relapsing–Remitting Multiple Sclerosis

Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-β1a and Circulating Proinflammatory Cytokines in Relapsing–Remitting Multiple Sclerosis

Phosphofructokinase-1 Negatively Regulates Neurogenesis from Neural Stem Cells

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

Contact Info

Product

Resources

About