Metabolic profile associated with glucose and cholesterol lowering effects of berberine in Sprague–Dawley rats

In this study, we present an integrated strategy to deconvolute the metabolic signatures associated with the cholesterol lowering effect of berberine in the livers of Sprague?CDawley rats. The rats were dosed with berberine at 50?mg/kg. Urine samples and liver tissues were collected for the analysis of metabolite contents, while livers and kidneys were collected for histopathology. Metabolites such as fatty acids, cholesterol, glucose and others in liver were analyzed by gas chromatography/mass spectrometry. The urinary metabolites were analyzed using targeted profiling with liquid chromatography/tandem mass spectrometry and non-targeted profiling with proton nuclear magnetic resonance (¹H NMR). Our results demonstrated that analysis of metabolites in rat urine samples using liquid chromatography/mass spectrometry (LC/MS) and ¹H NMR produced complementary, consistent and reliable results. The administration of berberine resulted in a reduction of glucose, maltose, fatty acids (saturated and unsaturated) and cholesterol in the rat liver samples. The analysis of urinary metabolic profiles on different days showed that before the cholesterol reduction in the rat livers, a high rate of carbohydrate usage was found to be an early event (day 2). The results suggested that the animals utilized alternative energy sources by altering the synthesis and consumption of amino acids and fatty acids. In addition, changes in the level of glutamine for the treated animals on day 2 suggested that glutamine and glutamate metabolism could be affected. Since glutamine is a precursor for nucleotides synthesis and nucleotides are required for cell growth and replication, the results are consistent with the observed cholesterol lowering effect and weight reduction. Finally, our results demonstrated that the combination of LC/MS and ¹H NMR provided a unique metabolic profile associated with the cholesterol lowering effect of berberine in rat livers.     

Mutagenic activity of metabolites contained in the plasma of Sprague—Dawley rats treated with cyclophosphamide

In the present study we have tried to add some new results to those data previously obtained by Natarajan et al. (1983) and Darroudi and Natarajan (1985), where they have used in vivo metabolization and cytogenetic testing for in vitro analysis of xenobiotic compounds. Sprague-Dawley rats were treated intraperitoneally with 2.5, 5.0, 10.0 and 20.0 mg/kg b.w. of cyclophosphamide in order to obtain plasma containing active metabolites of the drug. The mutagenic activity was assessed by estimating the frequencies of sister-chromatid exchanges (SCE) in human and rat lymphocytes. No influence of animal age was observed on the metabolism of cyclophosphamide, which could be detected by SCE analysis. The increase in SCE frequencies in both human and rat lymphocytes was dependent on the doses applied. SCE frequencies are highly variable among individuals, showing statistically significant differences. The same effect, but to a lesser extent, was also found in rats. Rat lymphocytes can be assumed to be good biological material for chemical mutagenesis, as the animals can be maintained at almost constant experimental conditions. However, rat lymphocytes do not grow well in in vitro cultures. These data contribute to the preview proposal that combining metabolism in vivo and chromosome SCE analysis in vitro can be regarded as an important and very sensitive system to detect the mutagenic activity of low-dose exposure to chemical compounds requiring metabolic activation.     

Short-term but not long-term hypoglycaemia enhances plasma levels and hepatic expression of HSP72 in insulin-treated rats: an effect associated with increased IL-6 levels but not with IL-10 or TNF–α

The inducible expression of the 70-kDa heat shock proteins (HSP70) is associated with homeostatically stressful situations. Stresses involving sympathetic nervous system (SNS) activation, including α₁-adrenergic agonists and physical exercise, are capable of inducing HSP70 expression and release of the HSP70 inducible form, HSP72. However, whether hypoglycaemia is capable of influencing HSP70 status under a stressful situation such as insulin-induced hypoglycaemia (IIH), which also involves SNS activation, is unsettled. Hence, we decided to investigate whether the predominant signal for HSP70 expression and delivery into the blood comes from either low glucose, high insulin, or both during short-term IIH (STIIH) and long-term IIH (LTIIH). Our data indicated that low glucose level (up to 1.56 ± 0.14 mM), but not insulin, is the triggering factor responsible for a dramatic rise in HSP72 plasma concentrations (from 0.15 ± 0.01 in fed state to 0.77 ± 0.13 ng/mL during hypoglycaemic episodes). This was observed in parallel with up to 7-fold increases in interleukin-6 (IL–6) but not interleukin-10 (IL–10) or tumour necrosis factor-α (TNF–α) at STIIH. Together, the observations may suggest that HSP72 is released under hypoglycaemic conditions as a part of the homeostatic stress response, whereas at long-term, both hypoglycaemia and insulin may influence HSP72 expression in the liver, but not in kidneys. Secreted extracellular HSP72 (eHSP72) may be purely a danger signal to all the tissues of the body for the enhancement of immune and metabolic surveillance state or actively participates in glycaemic control under stressful situations.     

Whole blood n-3 fatty acids are associated with executive function in 2–6-year-old Northern Ghanaian children

Several studies demonstrate the importance of essential fatty acids (EFAs), and the long chain polyunsaturated FA docosahexaenoic acid (DHA), on cognition and brain development. The objective of this study was to investigate the relationship between whole-blood FAs and executive function in children from Northern Ghana. A total of 307, 2-to-6-year-old children attempted the dimensional change card sort (DCCS) task to assess executive function, and dried blood spot samples were collected and analyzed for FA content. Significant differences in mean % total whole-blood fatty acids were observed between children who could not follow directions on the DCCS test (49.8% of the sample) and those who could (50.2% of the sample). Positive associations with DCCS performance were observed for DHA (β=0.25, P=.06), total n-3 (β=0.17, P=.06) and dihomo-gamma-linolenic acid (DGLA; β=0.60, P=.06). Children with the highest levels of total n-3 and DHA were three and four times, respectively, more likely to pass at least one condition of the DCCS test of executive function than those with the lowest DHA levels. The results of this study indicate an association between n-3 FAs and high-level cognitive processes in children two to six years of age, providing impetus for further studies into possible interventions to improve EFA status of children in developing countries.     

Futile cycle of β-oxidation and de novo lipogenesis are associated with essential fatty acids depletion in lipoatrophy

Total absence of adipose tissue (lipoatrophy) is associated with the development of severe metabolic disorders including hepatomegaly and fatty liver. Here, we sought to investigate the impact of severe lipoatrophy induced by deletion of peroxisome proliferator-activated receptor gamma (PPARγ) exclusively in adipocytes on lipid metabolism in mice. Untargeted lipidomics of plasma, gastrocnemius and liver uncovered a systemic depletion of the essential linoleic (LA) and α-linolenic (ALA) fatty acids from several lipid classes (storage lipids, glycerophospholipids, free fatty acids) in lipoatrophic mice. Our data revealed that such essential fatty acid depletion was linked to increased: 1) capacity for liver mitochondrial fatty acid β-oxidation (FAO), 2) citrate synthase activity and coenzyme Q content in the liver, 3) whole-body oxygen consumption and reduced respiratory exchange rate in the dark period, and 4) de novo lipogenesis and carbon flux in the TCA cycle. The key role of de novo lipogenesis in hepatic steatosis was evidenced by an accumulation of stearic, oleic, sapienic and mead acids in liver. Our results thus indicate that the simultaneous activation of the antagonic processes FAO and de novo lipogenesis in liver may create a futile metabolic cycle leading to a preferential depletion of LA and ALA. Noteworthy, this previously unrecognized cycle may also explain the increased energy expenditure displayed by lipoatrophic mice, adding a new piece to the metabolic regulation puzzle in lipoatrophies.     

The effect of losartan and carvedilol on renal haemodynamics and altered metabolism in fructose-fed Sprague–Dawley rats

The aim of this study is to assess the effects of losartan and carvedilol on metabolic parameters and renal haemodynamic responses to angiotensin II (Ang II) and adrenergic agonists in the model of fructose-fed rat. Thirty-six Sprague-Dawley rats were fed for 8 weeks either 20% fructose solution (F) or tap water (C) ad libitum. F or C group received either losartan or carvedilol (10 mg/kg p.o.) daily for the last 3 weeks of the study (FL and L) and (FCV and CV), respectively, then in acute studies the renal vasoconstrictor actions of Ang II, noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) were determined. Data, mean±SEM were analysed using ANOVA with significance at P <0.05. Losartan and carvedilol decreased the area under the glucose tolerance curve of the fructose-fed group. The responses (%) to NA, PE, ME and Ang II in F were lower (P <0.05) than C (F vs. C, 17±2 vs. 38±3; 24±2 vs. 48±2; 12±2 vs. 34±2; 17±2 vs. 26±2), respectively. L had higher (P <0.05) responses to NA and PE while CV had blunted (P <0.05) responses to NA, PE and Ang II compared to C (L, CV vs. C, 47±3, 9±2 vs. 38±3; 61±3, 29±3 vs. 48±2; 16±3, 4±3 vs. 26±2), respectively. FL but not FCV group had enhanced (P <0.05) responses to NA, PE and ME compared to F (FL vs. F, 33±3 vs. 17±2; 45±3 vs. 24±2; 26±3 vs. 12±2), respectively. Losartan and carvedilol had an important ameliorating effect on fructose-induced insulin resistance. Losartan treatment could be an effective tool to restore normal vascular reactivity in the renal circulation of the fructose-fed rat.     

Chronic citalopram treatment elevates serotonin synthesis in flinders sensitive and flinders resistant lines of rats,with no significant effect on Sprague–Dawley rats

The influence of citalopram on regional 5-hydroxytryptamine (serotonin, 5-HT) synthesis, one of the most important presynaptic parameters of serotonergic neurotransmission, was studied. Sprague–Dawley (SPD) rats were used as the controls, and Flinders Resistant Line (FRL) rats were used as auxiliary controls, to hopefully obtain a better understanding of the effects of citalopram on Flinders Sensitive Line (FSL; “depressed”) rats. Regional 5-HT synthesis was evaluated using a radiographic method with a labelled tryptophan analog tracer. In each strain of rats, the animals were treated with citalopram (10 mg/(kg day)) or saline for 14 days. The groups consisted of between fourteen and twenty rats. There were six groups of rats with citalopram (CIT) and saline (SAL) groups in each of the strains (SPD–SAL, SPD–CIT, FRL–SAL, FRL–CIT, FSL–SAL and FSL–CIT). A two-factor analysis of variance was used to evaluate the effect of the treatment c., SPD-SAL relative to SPD-CIT) followed by planned comparisons to evaluate the effect in each brain region. In addition, the planned comparison with appropriate contrast was used to evaluate a relative effects in SPD relative to FSL and FRL, and FSL relative to FRL groups. A statistical analysis was first performed in the a priori selected regions, because we had learned, from previous work, that it was possible to select the brain regions in which neurochemical variables had been altered by the disorder and subsequent antidepressant treatments. The results clearly show that citalopram treatment does not have an overall effect on synthesis in the control SPD rats; there was no significant (p > 0.05) difference between the SPD–SAL and SPD–CIT rats. In “depressed” FSL rats, citalopram produced a significant (p < 0.05) elevation of synthesis in seventeen out of thirty-four regions, with a significant (p < 0.05) reduction in the dorsal and median raphe. In the FRL rats, there was a significant (p < 0.05) elevation in the synthesis in twenty-two out of thirty-four brain regions, with a reduction in the dorsal raphe. In addition to these regions magnus raphe was different in the SPD and FSL groups, but it was on the statistical grounds identified as an outlier. There were significant changes produced in the FSL and FRL rats in thirteen out of seventeen a priori selected brain regions, while in the SPD rats, citalopram produced significant changes in only four out of seventeen a priori selected regions. The statistical evaluation also revealed that changes produced by citalopram in the FSL and FRL rats were significantly greater than those in the SPD rats and that there was no significant difference between the effect produced in the FSL and FRL rats. The presented results suggest that in “depressed” FSL rats, the antidepressant citalopram elevates 5-HT synthesis, which probably in part relates to the reported improved in behaviour with citalopram.     

Evaluation of acute corneal damage induced by 222-nm and 254-nm ultraviolet light in Sprague–Dawley rats

Two hundred twenty-two nanometres ultraviolet (UV) light produced by a krypton–chlorine excimer lamp is harmful to bacterial cells but not skin. However, the effects of 222-nm UV light exposure to the eye are not fully known. We evaluated acute corneal damage induced by 222- and 254-nm UV light in albino rats. Under deep anaesthesia, 6-week-old Sprague–Dawley albino rats were exposed to UV light. The exposure levels of corneal radiation were 30, 150, and 600?mJ/cm². Epithelial defects were detected by staining with fluorescein. Superficial punctate keratitis developed in corneas exposed to more than 150?mJ/cm² of UV light, and erosion was observed in corneas exposed to 600?mJ/cm² of UV light. Haematoxylin and eosin staining also showed corneal epithelial defects in eyes exposed to 254-nm UV light. However, no damage developed in corneas exposed to 222-nm UV light. Cyclobutane pyrimidine dimer-positive cells were observed only in normal corneas and those exposed to 254-nm UV light. Although some epithelial cells were stained weakly in normal corneas, squamous epithelial cells were stained moderately, and the epithelial layer that was detached from the cornea exposed to 600?mJ/cm² of light was stained intensely in corneas exposed to 254-nm UV light. In the current study, no corneal damage was induced by 222-nm UV light, which suggested that 222-nm UV light may not harm rat eyes within the energy range and may be useful for sterilising or preventing infection in the future.     

Role of saturated and unsaturated fatty acids on dicarbonyl–albumin derived advanced glycation end products in vitro

Amino Acids - Glycation is a non-enzymatic reaction that occurs between the free amino group of proteins and reducing sugars and/or lipids, leading to the formation of advanced glycation end...     

Green tea polyphenols modify gut-microbiota dependent metabolisms of energy,bile constituents and micronutrients in female Sprague–Dawley rats

Our recent metagenomics analysis has uncovered remarkable modifying effects of green tea polyphenols (GTP) on gut-microbiota community structure and energy conversion related gene orthologs in rats. How these genomic changes could further influence host health is still unclear. In this work, the alterations of gut-microbiota dependent metabolites were studied in the GTP-treated rats. Six groups of female SD rats (n=12/group) were administered drinking water containing 0%, 0.5%, and 1.5% GTP (wt/vol). Their gut contents were collected at 3 and 6 months and were analyzed via high performance liquid chromatography (HPLC) and gas chromatography (GC)-mass spectrometry (MS). GC–MS based metabolomics analysis captured 2668 feature, and 57 metabolites were imputatively from top 200 differential features identified via NIST fragmentation database. A group of key metabolites were quantitated using standard calibration methods. Compared with control, the elevated components in the GTP-treated groups include niacin (8.61-fold), 3-phenyllactic acid (2.20-fold), galactose (3.13-fold), mannose (2.05-fold), pentadecanoic acid (2.15-fold), lactic acid (2.70-fold), and proline (2.15-fold); the reduced components include cholesterol (0.29-fold), cholic acid (0.62-fold), deoxycholic acid (0.41-fold), trehalose (0.14-fold), glucose (0.46-fold), fructose (0.12-fold), and alanine (0.61-fold). These results were in line with the genomic alterations of gut-microbiome previously discovered by metagenomics analysis. The alterations of these metabolites suggested the reduction of calorific carbohydrates, elevation of vitamin production, decreases of bile constituents, and modified metabolic pattern of amino acids in the GTP-treated animals. Changes in gut-microbiota associated metabolism may be a major contributor to the anti-obesity function of GTP.     

Increased plasma levels of osteopontin are associated with activation of the renin–aldosterone system and with myocardial and coronary microvascular damage in dilated cardiomyopathy

In patients with dilated cardiomyopathy (DCM) abnormal myocardial blood flow (MBF) has been associated with coronary microvascular dysfunction. The aim of this study was to test the hypothesis that osteopontin (OPN) plasma levels could be associated with the activation of the renin–aldosterone system (RAS) in these patients and be involved in mediating myocardial and coronary damage. In 66 patients with idiopathic left ventricular dysfunction of variable severity the plasma levels of OPN were correlated with biomarkers of systemic metabolism, RAS activation, myocardial dysfunction and with clinical indexes of left ventricle (LV) function and perfusion obtained by 2D-echocardiography and PET. As compared to controls, patients showed a significant increase of inflammatory markers (OPN: 508 ± 30.8 ng/ml vs. 426.9 ± 16.4, p < 0.05 and interleukin (IL)-6: 1.71 ± 0.29 pg/ml vs. 0.38 ± 0.03 pg/ml, p < 0.001) and of indexes of cardiac damage. OPN levels were significantly correlated with the extent of microvascular dysfunction (MBF at rest: p = 0.01; during dipyridamole: p = 0.0003) and with plasma renin activity (PRA) (r = 0.26, p = 0.04). Both in patients with milder or more severe LV dysfunction lower MBF values were associated with higher OPN levels and PRA. These results suggest a interdependent role of RAS and vascular inflammation in cardiomyopathy.     

Interaction of diet and the masou salmon Δ5-desaturase transgene on Δ6-desaturase and stearoyl-CoA desaturase gene expression and N-3 fatty acid level in common carp (Cyprinus carpio)

The masou salmon Δ5-desaturase-like gene (D5D) driven by the common carp β-actin promoter was transferred into common carp (Cyprinus carpio) that were fed two diets. For P₁ transgenic fish fed a commercial diet, Δ6-desaturase-like gene (D6D) and stearoyl-CoA desaturase (SCD) mRNA levels in muscle were up-regulated (P < 0.05) 12.7- and 17.9-fold, respectively, and the D6D mRNA level in the gonad of transgenic fish was up-regulated 6.9-fold (P < 0.05) compared to that of non-transgenic fish. In contrast, D6D and SCD mRNA levels in transgenic fish were dramatically down-regulated (P < 0.05), 50.2- and 16.7-fold in brain, and 5.4- and 2.4-fold in liver, respectively, in comparison with those of non-transgenic fish. When fed a specially formulated diet, D6D and SCD mRNA levels in muscle of transgenic fish were up-regulated (P < 0.05) 41.5- and 8.9-fold, respectively, and in liver 6.0- and 3.3-fold, respectively, compared to those of non-transgenic fish. In contrast, D6D and SCD mRNA levels in the gonad of transgenic fish were down-regulated (P < 0.05) 5.5- and 12.4-fold, respectively, and D6D and SCD mRNA levels in the brain were down-regulated 14.9- and 1.4-fold (P < 0.05), respectively, compared to those of non-transgenic fish. The transgenic common carp fed the commercial diet had 1.07-fold EPA, 1.12-fold DPA, 1.07-fold DHA, and 1.07-fold higher observed total omega-3 fatty acid levels than non-transgenic common carp. Although these differences were not statistically different (P > 0.05), there were significantly (P < 0.10) higher omega-3 fatty acid levels when considering the differences for all of the individual omega-3 fatty acids. The genotype × diet interactions observed indicated that the potential of desaturase transgenesis cannot be realized without using a well-designed diet with the needed amount of substrates.     

The insulin sensitizing effects of PPAR-γ agonist are associated to changes in adiponectin index and adiponectin receptors in Zucker fatty rats

The adiponectin high molecular weight isoform (HMW-adp) and its relation with the other adiponectin isoforms (adiponectin index, S(A)), have been identified as essential for the adiponectin insulin sensitizing effects. The objective of this study is to gain further insight on the effect of the insulin sensitizing agents, PPAR-γ agonists, on the distribution of the adiponectin isoforms and the adiponectin receptors, adipoR1 and adipoR2 in an animal model of obesity and insulin resistance. To achieve the objective, Zucker fatty rats were treated with pioglitazone, rosiglitazone or placebo for six weeks. At the end of the treatment, total adiponectin, adiponectin isoforms and adiponectin receptors expression were measured. In order to see the possible relation with insulin sensitivity parameters, HOMA-IR, muscle insulin-stimulated glucose transport, muscle GLUT4 and plasma free fatty acids were also measured. The two glitazones improved insulin sensitivity and both muscle insulin-stimulated glucose transport and GLUT4 total content. Total plasma adiponectin and visceral fat HMW-adp were increased only by pioglitazone. On the other hand, both glitazones changed the distribution of adiponectin isoforms in plasma, leading to an increase in the S(A) of 21% by pioglitazone and 31% by rosiglitazone. Muscle adipoR1 expression was increased by both glitazones whereas liver adipoR2 expression was increased by rosiglitazone and tended to increase in the pioglitazone group. The insulin sensitizing action of glitazones is mediated, at least in part, by their effect on muscle insulin-stimulated glucose transport and by their direct influence on the adiponectin index and the adiponectin receptors expression.     

Higher de novo synthesized fatty acids and lower ω3- and ω6-long-chain polyunsaturated fatty acids in umbilical vessels of women with preeclampsia and high fish intakes

Umbilical veins (UV) and arteries (UA) of preeclamptic women in Curaçao harbor lower long-chain polyunsaturated fatty acids (LCP). The present aim was to test these findings in Mwanza (Tanzania), whose inhabitants have high LCPω3 and LCPω6 intakes from Lake Victoria fish. Women with preeclampsia (n=28) in Mwanza had lower PUFA and higher 20:0 in UV and UA, compared with normotensive/non-proteinuric controls (n=31). Their UV 22:6ω3, 22:4ω6, LCPω6, ω6, and LCPω3+ω6 were lower, while saturated FA, potentially de novo synthesized FA (Σde novo) and (Σde novo)/(LCPω3+ω6) ratio were higher. Their UA had higher 16:1ω7, ω7, 18:0, and 16:1ω7/16:0. Umbilical vessels in Mwanza had higher 22:6ω3, LCPω3, ω3, and 16:0, and lower 22:5ω6, 20:2ω6, 18:1ω9, and ω9, compared to those in Curaçao. Preeclampsia in both Mwanza and Curaçao is characterized by lower LCP and higher Σde novo. An explanation of this might be placental dysfunction, while the similarity of umbilical vessel FA-abnormalities in preeclamptic and diabetic pregnancies suggests insulin resistance as a common denominator.     

Increased Δ5- and Δ6-desaturase, cyclooxygenase-2, and lipoxygenase-5 expression and activity are associated with fatty acid and eicosanoid changes in cystic fibrosis

Patients with cystic fibrosis consistently demonstrate selective abnormalities in essential fatty acid concentrations, including decreased linoleate (LA) and docosahexaenoate (DHA), with variably increased arachidonate (AA). These changes appear important for the pathophysiology of the disease. However, the mechanisms of these changes are not clearly understood. The current study demonstrates that metabolism of LA and alpha linolenate (LNA) to AA and eicosapentaenoate (EPA), respectively, are significantly increased in two different cell culture models of cystic fibrosis. These changes correlated with increased expression of fatty acid Δ5- and Δ6-desaturases, key enzymes in this metabolic pathway. In contrast, cystic fibrosis cells showed decreased metabolism of AA and EPA to docosapentaenoate (DPA) and docosahexaenoate (DHA), respectively, although metabolism of 22:5n-3 to DHA was relatively unchanged. In addition, the expression and activity of both cyclooxygenase-2 and lipoxygenase-5 was markedly increased in these cells. Taken together, these findings are consistent with the conclusion that the diminished LA and increased AA in cystic fibrosis result from increased metabolism of LA, while the observed decrease in DHA is at least partly due to decreased elongation and desaturation beyond EPA.     

Poor acute outcome in congestive heart failure is associated with increases in the plasma static oxidation–reduction potentials (sORP) in men but not in women

Objectives: In congestive heart failure (CHF), men are younger, more likely to have reduced ejection fraction (HF-rEF), and to be diabetic compared to women. Despite this, sex differences in oxidative stress have yet to be explored in CHF.

Methods: Data from 67 males and 63 females hospitalized for CHF were collected. Static oxidation–reduction potential (sORP), a relative indicator of oxidative stress, and capacity ORP (icORP), a relative indicator of antioxidant capacity, were measured from plasma samples. We examined whether sex modified the relationship between ORP and hospital discharge disposition (poor outcome: death, hospice), along with other demographics, medications, and diagnostic parameters.

Results: Males with poor outcomes had higher sORP and icORP values than females (P?P?>?0.05). Males were younger and more likely to have HF-rEF and diabetes. Controlling for these variables did not account for the sex differences in ORP measures. Regardless of sex, higher creatinine was related to higher sORP and icORP, while lower magnesium and potassium were related to higher sORP and icORP, respectively.

Discussion: Increases in sORP during CHF are partially affected by sex and acute outcomes, but are also related to variables without sexual biases.     

Knockdown of α-synuclein in cerebral cortex improves neural behavior associated with apoptotic inhibition and neurotrophin expression in spinal cord transected rats

Spinal cord injury (SCI) often causes severe functional impairment with poor recovery. The treatment, however, is far from satisfaction, and the mechanisms remain unclear. By using proteomics and western blot, we found spinal cord transection (SCT) resulted in a significant down-regulation of α-synuclein (SNCA) in the motor cortex of SCT rats at 3 days post-operation. In order to detect the role of SNCA, we used SNCA-ORF/shRNA lentivirus to upregulate or knockdown SNCA expression. In vivo, SNCA-shRNA lentivirus injection into the cerebral cortex motor area not only inhibited SNCA expression, but also significantly enhanced neurons’ survival, and attenuated neuronal apoptosis, as well as promoted motor and sensory function recovery in hind limbs. While, overexpression SNCA exhibited the opposite effects. In vitro, cortical neurons transfected with SNCA-shRNA lentivirus gave rise to an optimal neuronal survival and neurite outgrowth, while it was accompanied by reverse efficiency in SNCA-ORF group. In molecular level, SNCA silence induced the upregulation of Bcl-2 and the downregulation of Bax, and the expression of NGF, BDNF and NT3 was substantially upregulated in cortical neurons. Together, endogenous SNCA play a crucial role in motor and sensory function regulation, in which, the underlying mechanism may be linked to the regulation of apoptosis associated with apoptotic gene (Bax, Bcl2) and neurotrophic factors expression (NGF, BDNF and NT3). These finds provide novel insights to understand the role of SNCA in cerebral cortex after SCT, and it may be as a novel treatment target for SCI repair in future clinic trials.