Objective To explore the change in heme oxygenase-1 (HO-1) level in cerebrospinal fluid(CSF)and serum in patients with mild cognitive impairment(MCI),and the correlation between HO-1 and the rating scale,to provide a new marker for the diagnosis of MCI.Methods The HO-1 levels in CSF and serum in 45 MCI patients (MCI group) and 85 normal cases (control group) were analyzed with sensitive enzyme linked immunosorbent assays (ELISA).MMSE and MoCA scores were evaluated.Results The level of HO-1 was higher in MCI group than in control group both in CSF [(631.38±32.17)vs(480.75±17.98)ng/ L,P＜0.05],and in serum [(612.52±111.48)vs.(384.16±56.86)ng/ L,P＜0.05].The MCI and normal people HO-1 level had no significant difference between CSF group and serum group (P＞0.05).In MCI group,the levels of serum and CSF HO-1 had a positive correlation with MMSE scores (P＜0.05),but had no obvious correlation with MoCA scores (P＞0.05).In the normal group,the level of HO-1 was negatively related with MMSE scores in serum and CSF,and with MoCA scores in CSF (P＜0.05),but no obvious correlation in serum (P＞0.05).The levels of serum and CSF HO-1 had no obvious correlation with age in both groups (P＞0.05).Conclusions HO-1 concentration in both CSF and serum is significantly higher in MCI group than in normal group,and positively related with MMSE score.Thus the increase of HO-1concentration in both CSF and/or serum might be a new marker for the diagnosis of MCI.

OBJECTIVES: Cerebral infarction is a subtype of stroke with high incidence and disability rate. Ischemia reperfusion injury (IRI) is the key point of cerebral infarction treatment. UbiA prenyltransferase domain containing 1 (UBIAD1) is a kind of enzyme with various biological functions including electron transport in mitochondrial respiratory chain, lipid metabolism, and oxidative stress which are related to IRI. The purpose of this study aims to determine the neuroprotective effects and the underlying mechanisms of UBIAD1 in cerebral IRI. METHODS: We employed oxygen-glucose deprivation/reoxygenation (OGD/R) model in mouse neuroblastoma Neuro2a (N2a) cells to mimic cerebral IRI. Lentivirus vector over-expressed UBIAD1 was transfacted into N2a cells to maintain high and stable expression of UBIAD1. In the first part of the experiment, N2a cells were divided into 5 groups: A non-OGD (N2a cells without exposure to OGD) group, groups of reoxygenation 0, 4, 12 and 24 h after 4 h of OGD, respectively. In the second part of the experiment, N2a cells were divided into 6 groups: A Con (normal cell)+non-OGD group, an EV (cell transfected with empty vector)+non-OGD group, an OE (over-expressed UBIAD1)+non-OGD group, a Con+OGD/R group, an EV+OGD/R group, and an OE+OGD/R group. In the third part, the N2a cells were divided into 8 groups: A Con+non-OGD group, an OE+non-OGD group, a Con+non-OGD+nNOS inhibitior 7-nitroindazole (7-NI) group, an OE+non-OGD+7-NI group, a Con+OGD/R group, an OE+OGD/R group, a Con+OGD/R+7-NI group, and an OE+OGD/R+7-NI group. The morphological changes of Golgi apparatus were observed under the confocal laser scanning microscope. The mRNA and protein levels of UBIAD1, secretory pathway Ca²⁺-ATPase isoform 1 (SPCA1), and NOS were determined by real-time PCR and Western blotting, respectively. Cell apoptosis rate was detected with flow cytometry; cell viability was detected with MTT assay, and NO release was determined with Griess assay. RESULTS: Compared with the non-OGD group, the expression levels of UBIAD1 mRNA and protein in N2a cells in the groups of 0, 4, 12 and 24 h reoxygenation after OGD 4 h decreased significantly (P<0.05 or P<0.01), and the longer the reoxygenation time, the more significant the reduction of UBIAD1 expression. Compared with the Con+OGD/R group and the EV+OGD/R group, mRNA and protein levels of UBIAD1 and SPCA1 were increased (P<0.05 or P<0.01), the apoptosis rate was decreased (all P<0.01), and the cell viability was increased (all P<0.01) in the OE+OGD/R group. The Golgi fragmentation was less in the OE+OGD/R group than that in the Con+ OGD/R group and the EV+OGD/R group. The mRNA and protein levels of endothelial NOS (eNOS) and neuronal NOS (nNOS) were decreased (P<0.05 or P<0.01), and the level of NO was decreased (all P<0.01) in the groups over-expressed UBIAD1 (OE+non-OGD group vs Con+non-OGD group, OE+OGD/R group vs Con+OGD/R group). The level of NO and apoptosis rate of N2a cells were decreased (all P<0.01) in the the groups pretreated with 7-NI (Con+OGD/R+7-NI group vs Con+OGD/R group, OE+OGD/R+7-NI group vs OE+OGD/R group). CONCLUSIONS UBIAD1 may exerts protective effects on OGD/R induced N2a cells by ameliorating Golgi apparatus dysfunction via the nNOS/NO pathway.
Animals ; Mice ; Cell Survival ; Cerebral Infarction ; Dimethylallyltranstransferase ; Glucose ; Lipid Metabolism ; Oxygen ; Nitric Oxide/metabolism*