Human Thymic Involution and Aging in Humanized Mice.

Thymic involution is an important factor leading to the aging of the immune system. Most of what we know regarding thymic aging comes from mouse models, and the nature of the thymic aging process in humans remains largely unexplored due to the lack of a model system that permits longitudinal studies of human thymic involution. In this study, we sought to explore the potential to examine human thymic involution in humanized mice, constructed by transplantation of fetal human thymus and CD34+ hematopoietic stem/progenitor cells into immunodeficient mice. In these humanized mice, the human thymic graft first underwent acute recoverable involution caused presumably by transplantation stress, followed by an age-related chronic form of involution. Although both the early recoverable and later age-related thymic involution were associated with a decrease in thymic epithelial cells and recent thymic emigrants, only the latter was associated with an increase in adipose tissue mass in the thymus. Furthermore, human thymic grafts showed a dramatic reduction in FOXN1 and AIRE expression by 10 weeks post-transplantation. This study indicates that human thymus retains its intrinsic mechanisms of aging and susceptibility to stress-induced involution when transplanted into immunodeficient mice, offering a potentially useful in vivo model to study human thymic involution and to test therapeutic interventions.

Increase in penguin populations during the Little Ice Age in the Ross Sea, Antarctica.

Penguins are an important seabird species in Antarctica and are sensitive to climate and environmental changes. Previous studies indicated that penguin populations increased when the climate became warmer and decreased when it became colder in the maritime Antarctic. Here we determined organic markers in a sediment profile collected at Cape Bird, Ross Island, high Antarctic, and reconstructed the history of Adélie penguin colonies at this location over the past 700 years. The region transformed from a seal to a penguin habitat when the Little Ice Age (LIA; 1500-1800 AD) began. Penguins then became the dominant species. Penguin populations were the highest during ca. 1490 to 1670 AD, a cold period, which is contrary to previous results in other regions much farther north. Different responses to climate change may occur at low latitudes and high latitudes in the Antarctic, even if for same species.

Clinical analysis of stages of HBV infection in 100 cases of lymphoma.

OBJECTIVE: HBV infection may cause damage to the immune system and induce lymphomas as a result. Some scholars have indicated that HBsAg(+) reflecting HBV infection may have a relationship with lymphoma development. This study was designed to find out the specific stage of HBV infection which may be related to lymphoma. METHODS: HBV serum markers, including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb were tested among 100 lymphoma patients and 100 other patients who were diagnosed with non-lymphoma diseases in the First Hospital of Jilin University from 2010.1.1 to 2012.12.31. Three subgroups were established depending on different combinations of HBV serum markers. Subgroup 1 was HBsAg(+) representing the early stage of HBV infection. Subgroup 2 was HbsAb(+) representing convalescence and Subgroup 3 was "HbsAg and HbsAb negative combined with other positive markers" representing the intermediate stage of HBV infection. Chi square tests were used to compare the rates of three subgroups in lymphoma and control groups. RESULTS: The rates of Subgroup were 13% and 5% respectively, an association between HBsAg and lymphoma being found (P<0.05). There was no difference between rate of Subgroup 2 of lymphoma group (15%) and that of control group (16%). In lymphoma group and control group , the rate of Subgroup 3 was different (12% vs 4%). This evidence was not specific to T cell lymphoma, B cell lymphoma or Hodgkin's lymphoma. CONCLUSIONS: Among serum markers of HBV, the combination of serum markers representing the early stage and intermediate stage of HBV infection have a relationship with lymphoma. Convalescence from HBV infection appears to have no relationship with lymphoma.

[MAX-DOAS measurements of NO2 column densities and vertical distribution at Ny-Alesund, Arctic during summer].

The multi-axis differential optical absorption spectroscopy (MAX-DOAS), one of the remote sensing techniques for trace gases measurements, is sensitive to the lower atmosphere by eliminating the influence of stratosphere retrieved from zenith-sky spectroscopy. Ground-based MAX-DOAS measurements were carried out to observe NO2 at Ny-Alesund, Arctic from 5th Jul to 1st Aug 2011. The differential slant column densities (DSCDs) of NO2 at four off-axis angles showed typical pattern of tropospheric absorbers. Based on the assumption that NO2 was well mixed in 0-1 km of the troposphere, the mean mixing ratio of NO2 during the measurement period was 1.023E11 molec x cm(-3). The fluctuation of NO2 might be related to the fossil fuel combustions and the photochemical reactions. The vertical distribution of NO2 at 0-3 km showed that NO2 was mainly originated from boundary layer of sea surface.

[The retrieval of ozone column densities by passive differential optical absorption spectroscopy during summer at Zhongshan Station, Antarctic].

Daily ozone column densities were monitored by Passive DOAS (differential optical absorption spectroscopy) from December 10th, 2008 to Feb 19th, 2009 at Zhongshan Station, Antarctic (69 degrees 22'24" S, 76 degrees 22'14" E). Considering the absorption of O3, OClO, NO2, O4, BrO and the Ring effect, ozone slant column densities were retrieved using the zenith scattered sunlight as the light source. The results showed that there was no obvious "ozone hole" during the monitoring period, but ozone VCD (vertical column density) had greatly changed within short time scale, especially in middle December and early February. The analysis of passive DOAS and Brewer measurements of ozone VCD showed good agreement with the correlative coefficient of 0.863, while satellite board OMI measurements with the correlative coefficient of 0.840, which confirmed the validity of the monitoring of Passive DOAS.

[Analysis of methylmercury in biological guano by the optimized atomic fluorescence spectrometry coupled with microwave assisted extraction].

The analytical method for the determination of methylmercury in seabird excrements was established using atomic fluorescence spectrometry coupled with microwave-assisted extraction In general, temperature and hydrochloric amount are the most important influencing factors on the extraction of MeHg in the samples, and the present paper optimized these two parameters. The result showed that 120 degrees C and 200 microL 6 mol x L(-1) hydrochloric acid are the best extraction conditions. Under these experimental conditions, the relative standard deviation (RSD) values of reduplicative analyses on standard reference material (human hair powder) and the same seabird excrement sample were 0.74% and 6.61% respectively, and their percent recoveries were over 90%. The combination of microwave-assisted extraction and atomic fluorescence spectrometry has many advantages such as simple operation, high sensitivity, low detection limit and low cost, therefore, it is suitable for rapid separation and analysis of trace methylmercury composition in the biological guanos. Using this method, we analyzed the methylmercury contents in the ancient and fresh seabird droppings taken from Xisha Islands of South China Sea, and the result showed that the Xisha guanos were rich in methylmercury and the large input of seabird guanos will cause serious environmental contamination in the remote island ecosystem of Xisha Islands.

A 700-year record of mercury in avian eggshells of Guangjin Island, South China Sea.

Ancient eggshells over the past 700 years were extracted from an ornithogenic sediment profile on Guangjin Island, South China Sea. Based on SEM and nitrogen isotope analyses, we determined that neither post-depositional processes nor seabirds' dietary changes had a large influence on eggshell Hg levels. The historical change of Hg in these eggshells was reconstructed. Eggshell Hg was a marker for past Hg deposition in marine environment. The eggshell Hg showed three small peaks at around 1300AD, 1600 AD and 1700-1750AD and rapid increase since 1800 AD. Before 1970 AD the Hg deposition in the Xisha area had global distribution characteristics, with increased Hg emissions due to global anthropogenic activities in industrial times. However, after 1970 AD, a further sharp increase up to present day occurred, implying that the Hg production center had gradually shifted from Europe and America to Asia.

[Records and sources of mercury pollution over the past 200 years in Ny-Alesund, Arctic].

Hg pollution has become a global problem since the industrial revolution. In this study,we collected a pond sediment core rich in moss residues from the Ny-Alesund of Svalbard, and determined the content and flux of Hg in the sediments. Combined with 210Pb and 137Cs dating,we reconstructed the changes of Hg concentration and depositional flux in the recent 200 years,and focused on the main controlling factors on the elevated inputs of Hg since the 1850s. The results show that the Hg contents increase significantly since the World Industrial Revolution. The highest value of Hg is up to 180 ng x g(-1) in the surface sediments, and the ratios of anthropogenic Hg increase from 30% to 90%, thus the input of anthropogenic Hg has become a main source of total mercury in the study area. The range of Hg deposition flux is between 8-20 microg x (m(2) x a)(-1) in past 200 years, and show three distinct peaks,corresponding to 1800 s, 1880 s and 1970 s. Compared the historical Hg deposition flux with the records of local coal combustion and globe Hg production, we suggest that the anthropogenic Hg is mainly derived from the long-range atmosphere Hg transport, whereas the influence of local coal mining is likely minor. The Ny-Alesund has similar Hg pollution degree with Sweden, Canada and other circum-arctic areas, but obviously higher than Greenland and significantly lower than America and Russia,as well as other industrialized countries.

[A study on decreasing the instrument detection limit of atomic fluorescence spectrometry (AFS-930) for Hg].

In the present study, the detection limit of atomic fluorescence spectrometry (AFS-930) was decreased to 2 ng x L(-1) (n=6) based on several optimizing modifications, including that the sub-high voltage of photomultiplier tube and the current of hollow-cathode lamp were elevated to 280 V and to 30 mA, respectively, and the height of atomization cell was set as 10 mm; In addition, the concentration of KBH4 was decreased to 0.5% (KOH 0.2%). With the optimized parameters, a good standard curve of Hg concentration versus intensity of fluorescence (If) could been obtained readily, after that, a 4-ng x L(-1)-Hg water samples was measured accurately with a little relative standard deviation (RSD) of <5%, while for approximately 2-ng x L(-1)-Hg waters the RSD varied within a wide range of 10.9%-27.2%, likely due to the absorption of Hg by polyethylene vessels used in this study and/or due to the contamination by analysis grade reagents used in this study. By using low-absorption polytetrafluoroethylene (PTFE) materials and the guaranteed reagents, the instrument detection limit was further decreased to 1 ng x L(-1) (n=10).

[Effects of exercise on JNK phosphorylation and expression in skeletal muscle of rats].

AIM: To investigate the effects of exercise on JNK phosphorylation, protein and gene expression. METHODS: Male rats were randomly divided into control and trained groups. The trained rats were submitted to 1 h or 1.5 h of exercise daily and had a fragment of their excised gastrocenemius muscle, 24 h or 48 h after the last training session. The train lasted for 7 weeks. The changes in the expressions of JNK and p-JNK were determined by Western blotting. The expression of JNK mRNA was determined by RT-PCR. RESULTS: Glucose tolerance test found that blood insulin concentration was decreased with exercise training. Exercise led to a marked increase in p-JNK of trained groups 24 hours after exercise in rats that exercised for 1 hour per day and 24 and 48 hours after the exercise in those that exercised for 1.5 hours per day as compared with controls, and the protein expression of JNK significantly increased 24 and 48 hours after the exercise in rats that exercised for 1.5 hours per day. JNK mRNA was increased by exercise 1.5 h/d, 24 h after the last training session. CONCLUSION: Exercise could increase muscle responsiveness to insulin, improving the total JNK and p-JNK and mRNA expression.

Lead-induced stress response in endoplasmic reticulum of astrocytes in CNS.

ABSTRACT Lead is one of the most widespread toxicants in the environment, and its neurotoxicity contributes to a major medical issue. Numerous studies have shown that astrocytes are the main sites of Pb deposition in the central nervous system. A large amount of lead depositing in the astrocyte cells would result in the accumulation of unfolded protein in the endoplasmic reticulum (ER), which up-regulates the expression of molecular chaperones and meanwhile inhibits the cell-cycle progression and the transcription of certain proteins. The unfolded protein response (UPR) could down-regulate the expression of protein cyclinD1 and cause the stagnation of cell-cycle in primary-cultured astrocytes of rat. However, lead neither has obvious effects on the expression of C/EBP homologous protein (CHOP) nor achieves cell apoptosis in the progress of lead-induced UPR. When the stagnation of cell-cycle happens, glucose regulated protein of 78 kDa (GRP78) and other chaperones come to themselves to transport a body of unfolded-protein, consequently making cells survive.

The interaction of selenium and mercury in the accumulations and oxidative stress of rat tissues.

This study evaluates the interaction of selenium (Se) and mercury (Hg) in the accumulations and oxidative stress of rat tissues. Rats were divided into five groups including one control (n=9) and four treated groups including M-Hg (n=9), L-Hg+Se (n=11), M-Hg+Se (n=10), and H-Hg+Se (n=10) group. Treated groups of rats were instilled with different amounts of mercuric chloride (HgCl(2)) and dl-selenomethionine (SeMet) by gavage since pregnancy of their mothers. Atomic fluorescence spectroscopy (AFS) was applied for mercury and selenium quantification. Glutathione (GSH), malondialdehyde (MDA), and total superoxide dismutase (SOD) activity of tissues were detected using biochemical methods. Results showed that Hg was deposited mainly in kidney. Se could decrease Hg content in kidney but increase it in blood and liver. Hg decreased GSH and SOD and increased MDA levels in most detected tissues, while Se took on a counteraction effect in same tissues. This study suggests that interactions of Se and Hg affect their accumulation and Se may antagonize Hg-induced inhibition on organic activities.

Atmospheric Hexachlorocyclohexanes in the North Pacific Ocean and the adjacent Arctic region: spatial patterns, chiral signatures, and sea-air exchanges.

During the 2003 Chinese Arctic Research Expedition (CHINARE2003) from the Bohai Sea to the high Arctic (37 degrees N to 80 degrees N) aboard the icebreaker Xuelong (Snow Dragon), air samples were collected for the analysis of hexachlorocyclohexanes (HCHs) in the North Pacific Ocean and adjacent Arctic region. The sigma HCHs (alpha-HCH + gamma-HCH) ranged from 2.3 to 95.1 pg/m3 with the highest levels observed in Far East Asia (32.5 pg/m3), followed by the North Pacific Ocean (17.0 pg/m3) and the Arctic (7.3 pg/ m3). Compared to previous studies in the same areas in 1990s, our measurements were approximately 1 order of magnitude lower. Because of disproportionate chemical reduction and physical fractioning during long-range transport, the ratios of alpha-HCH to gamma-HCH (alpha/gamma-HCH) showed a significant increasing trend from low to high latitudes, suggesting thatthe alpha/gamma-HCH range of 4-7 could not be used to identify sources of technical HCHs especially in remote areas. The ratios of (+)-alpha-HCH to the sum of (+)-alpha-HCH and (-)-alpha-HCH were on average much more biased from 0.5 compared to previous observations in mid-1990s, indicating the exchange of atmospheric alpha-HCH with those in the oceans, where (+)-alpha-HCH was selectively depleted in biological degradation processes. Estimated fugacity ratios based on available data for both alpha-HCH and gamma-HCH further implied their net volatilization from seawater to air in the Arctic Ocean.

Effect of lead on ERK activity and the protective function of bFGF in rat primary culture astroglia.

OBJECTIVE: To observe the effects of lead on levels of phosphorylated extracellular signal regulated kinase (p-ERK) in the cytoplasm of primary cultures of rat astroglial cells and the possible protective effect of basic fibroblast growth factor (bFGF) on lead-induced effects. METHODS: The primary astroglia cells from 1~6 d old Wistar rats were cultured. The cells pretreated with the MEK1 (mitogen-activated protein kinase kinase 1) inhibitor PD98059 and bFGF, respectively, were exposed to Pb acetate of different concentrations for different times. Western blotting and reverse transcription polymerase chain reaction (RT-PCR) methods were used to detect the protein and mRNA expressions of ERK. RESULTS: mRNA expression for ERK peaked 15 min after initiation of lead exposure (P<0.05) and protein expression of p-ERK peaked at 30 min (P<0.05). ERK mRNA levels and p-ERK protein levels returned to baseline after 60 and 120 min of lead exposure, respectively (P>0.05). The increase in p-ERK levels in lead-treated cells could be inhibited by PD098059. Activation of ERK in the cells by lead was prevented by pretreatment with bFGF. Total ERK protein levels did not change under the same experimental conditions (P>0.05). CONCLUSION: Low-level lead exposure resulted in transient activation of ERK through the MEK pathway, which then returned to basal levels in the continued presence of lead. Exogenous bFGF protected ERK signaling components in astroglia from lead poisoning.

[Effects of endurance exercise on ERK1/2 phosphorylation and expression in skeletal muscle of rats].

AIM: To investigate the effects of exercise on phosphorylated and total ERK1/2, and mRNA of ERK2. METHODS: Male rats were randomly divided into control and trained groups. The trained rats were submitted to 1 h or 1.5 h of exercise daily and had a fragment of their excised gastroenemius muscle, 24 h or 48 h after the last training session. The train lasted for 7 weeks. The changes in the expressions of ERK1/2 and p-ERK1/2 were determined by Western blotting.The expression of ERK2 mRNA was determined by RT-PCR. RESULTS: Exercise led to a marked increase in p-ERK1/2 of trained groups as compared with controls, and increased ERK1/2 protein expression of training 1.5 h/d, 24 h and 48 h after the last training session. ERK2 mRNA was increased by exercise 1 h/d, 24 h and exercise 1.5 h/d, 24 h and 48 h after the last training session. Glucose tolerance test found that blood insulin concentration was decreased with exercise training. CONCLUSION: Endurance exercise could increase muscle responsiveness to insulin by improving the total ERK1/2 and p-ERK1/2, ERK2 mRNA expression.

Crystal structure of the MAP3K TAO2 kinase domain bound by an inhibitor staurosporine.

Mitogen-activated protein kinase (MAPK) signal transduction pathways are ubiquitous in eukaryotic cells, which transfer signals from the cell surface to the nucleus, controlling multiple cellular programs. MAPKs are activated by MAPK kinases [MAP2Ks or MAP/extracellular signal-regulated kinase (ERK) kinases (MEK)], which in turn are activated by MAPK kinase kinases (MAP3Ks). TAO2 is a MAP3K level kinase that activates the MAP2Ks MEK3 and MEK6 to activate p38 MAPKs. Because p38 MAPKs are key regulators of expression of inflammatory cytokines, they appear to be involved in human diseases such as asthma and autoimmunity. As an upstream activator of p38s, TAO2 represents a potential drug target. Here we report the crystal structure of active TAO2 kinase domain in complex with staurosporine, a broad-range protein kinase inhibitor that inhibits TAO2 with an IC50 of 3 mM. The structure reveals that staurosporine occupies the position where the adenosine of ATP binds in TAO2, and the binding of the inhibitor mimics many features of ATP binding. Both polar and nonpolar interactions contribute to the enzyme-inhibitor recognition. Staurosporine induces conformational changes in TAO2 residues that surround the inhibitor molecule, but causes very limited global changes in the kinase. The structure provides atomic details for TAO2-staurosporine interactions, and explains the relatively low potency of staurosporine against TAO2. The structure presented here should aid in the design of inhibitors specific to TAO2 and related kinases.

Inhibitory effect of Cd2+ on glycine-induced chloride current in rat hippocampal neurons.

The effects of cadmium (Cd(2+)) on glycine-induced Cl(-) current (I(Gly)) were investigated in acutely dissociated rat hippocampal CA1 neurons using the conventional whole-cell patch-clamp technique in this study. We found that Cd(2+) reversibly and concentration-dependently, reduced the amplitudes of I(Gly), with an IC(50) of 1.27 mM and Hill coefficient of 0.45. The depression of I(Gly) by Cd(2+) was independent of membrane voltage between -60 and +40 mV and did not involve a shift in the reversal potential of the current. A non-competitive inhibition was suggested by a double reciprocal plot of the effects of Cd(2+) on the concentration-response curve of the I(Gly). Since intracellular dialysis with 3mM Cd(2+) failed to modify I(Gly), it was suggested that the site of action of Cd(2+) is extracellular. The suppression of I(Gly) by Zn(2+) was unaffected by 3mM Cd(2+), which indicated that Zn(2+) and Cd(2+) bind to independent sites on glycine receptor. The results show that Cd(2+) decreases I(Gly) in acutely dissociated rat hippocampal neurons and the depression of I(Gly) by Cd(2+) may contribute to worsen the neurotoxicological impairment.

Reparatory effects of nicotine on NMDA receptor-mediated synaptic plasticity in the hippocampal CA1 region of chronically lead-exposed rats.

Activation of neuronal nicotinic acetylcholine receptors (nAChRs) modulates the induction of long-term potentiation (LTP): a possible cellular mechanism of learning. To investigate the effect of nicotine on synaptic plasticity in chronically lead-exposed rats, field excitatory postsynaptic potentials and paired-pulse facilitation (PPF) were recorded in the CA1 area of hippocampal slices from chronically lead-exposed 23-30-day-old rats. The results showed the following. (1) Nicotine (1 microm) facilitated the induction of LTP in CA1 by a weak tetanic stimulation (100 Hz, 20 pulses), which does not by itself produce LTP in lead-exposed rats. This effect was significantly suppressed by mecamylamine, a nicotinic antagonist, suggesting that the facilitation of LTP was through nAChRs. (2) The nicotine-facilitated LTP was blocked by dihydro-beta-erythroidine (DHbetaE), a non-alpha7 nAChR antagonist, whereas long-term depression (LTD) was produced by the combination of nicotine and methyllycaconitine, a alpha7-nAChR antagonist. This type of LTD was blocked by DHbetaE. This suggested that several nAChR subtypes were involved in the nicotine-facilitated synaptic plasticity. (3) Nicotine enhanced PPF in the hippocampal CA1 region, and the nicotine-facilitated LTP in lead-exposed rats was blocked by either d-(-)-2-amino-5-phosphonopentanoic acid, the N-methyl-d-aspartate (NMDA) receptor antagonist, or picrotoxin, an antagonist of gamma-aminobutyric acid(A) receptors. We suggest that nicotine-facilitated synaptic plasticity was due to the activation of NMDARs by disinhibition of pyramidal cells through presynaptic nAChRs. This may represent the cellular basis of nicotine-facilitated cognitive enhancement observed in chronically lead-exposed rats.

[The inhibitory effect of chronic lead exposure on CA1 LTP and ERK2 activity in rat hippocampal area].

AIM: To investigate the effect of chronic lead exposure on rat hippocampal CA1 LTP and alpha-Ca2+ /calmodulin-dependent protein kinase II (alpha-CaM K II) activity in vivo. METHODS: A stimulus bipolar electrode was placed on the Schaffer/Commissural fibers, with extra cellular microelectrode technique to record the population spike (PS) in the CA1 pyramidal, and we observed the changes of PS amplitude before and after the high frequency stimulation (HFS) of lower, mid and higher level lead exposure groups and the control group, respectively. The hippocampal CA1 alpha-CaM K II activity was determined by Western blots by using phosphorylation antibody. RESULTS: The average changes of PS after HFS of the control group, the lower, mid and higher level lead exposure groups were 162.5%, 105.2%, 86.8%, 83.0%, respectively (P < 0.01 vs. control). Defined control a-CaM K II activity as 100, that the lower, mid and higher level lead exposure groups were 62.0 +/- 3.7, 50.8 +/- 4.0, 43.3 +/- 4.1 (P < 0.01). CONCLUSION: Chronic lead exposure can inhibit CA1 LTP in vivo, and the decrease of alpha-CaMK II activity may play an important role in this mechanism.

Effects of extracellular delta-aminolaevulinic acid on sodium currents in acutely isolated rat hippocampal CA1 neurons.

The effects of delta-aminolaevulinic acid (ALA) on voltage-gated sodium channel (VGSC) currents (I(Na)) in acutely isolated hippocampal CA1 neurons from 10- to 12-day-old Wistar rats were examined by using the whole-cell patch-clamp technique under voltage-clamp conditions. ALA from 0.01 microm to 20 microm was applied to the recorded neurons. Low concentrations of ALA (0.01-1.0 microM) increased I(Na) amplitude, whereas high concentrations of ALA (5.0-20.0 microM) decreased it. The average I(Na) amplitude reached a maximum of 117.4 +/- 3.9% (n = 9, P < 0.05) with 0.1 microM ALA, and decreased to 78.1 +/- 3.8% (n = 13, P < 0.05) with 10 microm ALA. ALA shifted the steady-state activation and inactivation curves of I(Na) in the hyperpolarizing direction with different V0.5, suggesting that ALA could depress the opening threshold of the voltage-gated sodium channel (VGSC) and thus increase the excitability of neurons through facilitating the opening of VGSC. The time course of recovery from inactivation was significantly prolonged at both low and high concentrations of ALA, whereas either low or high concentrations of ALA had no significant effect on the attenuation of I(Na) during stimulation at 5 Hz, indicating that the effect of ALA on VGSC is state-independent. Furthermore, we found that application of ascorbic acid, which blocks pro-oxidative effects in neurons, could prevent the increase of I(Na) amplitude at low concentrations of ALA. Baclofen, an agonist of GABAb receptors, induced some similar effects to ALA on VGSC, whereas bicuculline, an antagonist of GABAa receptors, could not prevent ALA-induced effects on VGSC. These results suggested that ALA regulated VGSC mainly through its pro-oxidative effects and GABAb receptor-mediated effects.