Search

Excessive intake of manganese (Mn) may cause neurotoxicity. Sodium para-aminosalicylic acid (PAS-Na) has been used successfully in the treatment of Mn-induced neurotoxicity. The γ-aminobutyric acid (GABA) is related with learning and memory abilities. However, the mechanism of PAS-Na on improving Mn-induced behavioral deficits is unclear. The current study was aimed to investigate the effects of PAS-Na on Mn-induced behavioral deficits and the involvement of ultrastructural alterations and γ-aminobutyric acid (GABA) metabolism in the basal ganglia of rats. Sprague-Dawley rats received daily intraperitoneally injections of 15 mg/kg MnCl2.4H2O, 5d/week for 4 weeks, followed by a daily back subcutaneously (sc.) dose of PAS-Na (100 and 200 mg/kg), 5 days/week for another 3 or 6 weeks. Mn exposure for 4 weeks and then ceased Mn exposure for 3 or 6 weeks impaired spatial learning and memory abilities, and these effects were long-lasting. Moreover, Mn exposure caused ultrastructural alterations in the basal ganglia expressed as swollen neuronal with increasing the electron density in the protrusions structure and fuzzed the interval of neuropil, together with swollen, focal hyperplasia, and hypertrophy of astrocytes. Additionally, the results also indicated that Mn exposure increased Glu/GABA values as by feedback loops controlling GAT-1, GABAA mRNA and GABAA protein expression through decreasing GABA transporter 1(GAT-1) and GABA A receptor (GABAA) mRNA expression, and increasing GABAA protein expression in the basal ganglia. But Mn exposure had no effects on GAT-1 protein expression. PAS-Na treatment for 3 or 6 weeks effectively restored the above-mentioned adverse effects induced by Mn. In conclusion, these findings suggest the involvement of GABA metabolism and ultrastructural alterations of basal ganglia in PAS-Na’s protective effects on the spatial learning and memory abilities.

Sodium para-aminosalicylate (PAS-Na) was first applied successfully in clinical treatment of two manganism patients with good prognosis. However, the mechanism of how PAS-Na protects against Mn-induced neurotoxicity is still elusive. The current study was conducted to explore the effects of PAS-Na on Mn-induced basal ganglia astrocyte injury, and the involvement of amino acid neurotransmitter in vitro. Basal ganglia astrocytes were exposed to 500 μM manganese chloride (MnCl2) for 24 hr, following by 50, 150, or 450 μM PAS-Na treatment for another 24 hr. MnCl2 significantly decreased viability of astrocytes and induced DNA damages via increasing the percentage of tail DNA and Olive tail moment of DNA. Moreover, Mn interrupted amino acid neurotransmitters by decreasing Gln levels and increasing Glu, Gly levels. In contrast, PAS-Na treatment reversed the aforementioned Mn-induced toxic effects on basal ganglia astrocytes. Taken together, our results demonstrated that excessive Mn exposure may induce toxic effects on basal ganglia astrocytes, while PAS-Na could protect basal ganglia astrocytes from Mn-induced neurotoxicity.

Manganese (Mn) overexposure induced neurological damages, which could be potentially protected by sodium para-aminosalicylic acid (PAS-Na). In this study, we systematically detected the changes of divalent metal elements in most of the organs and analyzed the distribution of the metals in Mn-exposed rats and the protection by PAS-Na. Sprague Dawley (SD) rats received intraperitoneal injections of 15mg/kg MnCl2·4H2O (5d/week for 3 weeks), followed by subcutaneous (back) injections of PAS-Na (100 and 200mg/kg, everyday for 5 weeks). The concentrations of Mn and other metal elements [Iron (Fe), Copper (Cu), Zinc (Zn), Magnesium (Mg), Calcium (Ca)] in major organs (liver, spleen, kidney, thighbone and iliac bone, cerebral cortex, hippocampus and testes) and blood by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). The results showed that Mn overexposure significantly increased Mn in most organs, Fe and Zn in liver, Fe and Mg in blood; however decreased Fe, Cu, Zn, Mg and Ca in cortex, Cu and Zn in kidney, Cu and Mg in iliac bone, and Zn in blood. In contrast, PAS-Na treatment restored most changes particularly in cortex. In conclusion, excessive Mn exposure disturbed the balance of other metal elements but PAS-Na post-treatments could restore these alterations.

Objective: To explore the correlation between pathological and ultrasound changes applying conventional ultrasound, Color Doppler ultrasound andVirtual Touch Tissue Quantification (VTQ) technique in newborn hypoxic-ischemic brain damage (HIBD) rat models. To provide theoretical basis for early diagnosis and treatment of HIBD neonatal. Methods: A total of 90 newborn Wistar rats were divided into ischemia, asphyxia and control group according to different HIBD molding methods. Conventional ultrasound, Color Doppler ultrasound and VTQ were applied on 3 h, 12 h, 24 h, 48 h and 72 h postoperative. After the observation of 72 h, 10 rats in each group were randomly selected for pathological specimens production. The rest rats were raised for 30 days for neuroethology detection. Results: In ischemia group and asphyxia group, there were 4 deaths and 6 deaths in the modeling process; the mortality rate was 13.33% (4/30) and 20.00% (6/30) respectively. For ischemia group, the systoli velocity (Vs), diastolic velocity (Vd) and resistance index (RI) of right middle cerebral artery (MCA) were significantly decreased after operation (P

Excessive manganese (Mn) exposure is not only a health risk for occupational workers, but also for the general population. Sodium para-aminosalicylic acid (PAS-Na) has been successfully used in the treatment of manganism, but the involved molecular mechanisms have yet to be determined. The present study aimed to investigate the effects of PAS-Na on sub-chronic Mn exposure-induced impairments of spatial learning and memory, and determine the possible involvements of γ-aminobutyric acid (GABA) metabolism in vivo. Sprague-Dawley male rats received daily intraperitoneal injections MnCl2 (as 6.55 mg/kg Mn body weight, five days per week for 12 weeks), followed by daily subcutaneous injections of 100, 200, or 300 mg/kg PAS-Na for an additional six weeks. Mn exposure significantly impaired spatial learning and memory ability, as noted in the Morris water maze test, and the following PAS-Na treatment successfully restored these adverse effects to levels indistinguishable from controls. Unexpectedly, PAS-Na failed to recover the Mn-induced decrease in the overall GABA levels, although PAS-Na treatment reversed Mn-induced alterations in the enzyme activities directly responsible for the synthesis and degradation of GABA (glutamate decarboxylase and GABA-transaminase, respectively). Moreover, Mn exposure caused an increase of GABA transporter 1 (GAT-1) and decrease of GABA A receptor (GABAA) in transcriptional levels, which could be reverted by the highest dose of 300 mg/kg PAS-Na treatment. In conclusion, the GABA metabolism was interrupted by sub-chronic Mn exposure. However, the PAS-Na treatment mediated protection from sub-chronic Mn exposure-induced neurotoxicity, which may not be dependent on the GABA metabolism.

This study was conducted to investigate the protective effects of sodium p-aminosalicylic acid (PAS-Na) on learning and memory via increasing the number of basal forebrain choline acetyltransferase (ChAT) neurons in manganese (Mn)-exposed rats. Male Sprague Dawley rats were divided into following groups: the normal control I, II, and III groups, the model I, II, and III groups, low- and high-dose PAS-Na treatment (L- and H-PAS) group, PAS-Na prevention (PAS-P) group, and PAS-Na treatment (PAS-T) group. The model I, II, and III groups, L- and H-PAS, and PAS-T groups received intraperitoneal (i.p.) injection of 15 mg/kg manganese chloride tetrahydrate (MnCl2·4H2O) for 3 or 12 weeks, while the normal control I, II, and III groups received i.p. injection of an equal volume of saline; L- and H-PAS and PAS-T groups received back subcutaneous (s.c.) injection of PAS-Na (100 and 200 mg/kg) for the next 5 or 6 weeks, whereas model I and II group received back s.c. injection of an equal volume of saline. However, PAS-P group received back s.c. injection of 200 mg/kg PAS-Na + i.p. injection of 15 mg/kg MnCl2·4H2O for 12 weeks. Mn exposure significantly reduced the ability of spatial learning and memory capability, while PAS-Na prevention recovered it. Mn decreased the number of ChAT-positive neurons in vertical limb nucleus of the basal forebrain diagonal band/horizontal limb nucleus of the basal forebrain diagonal band and ChAT protein activity and treatment or prevention with PAS-Na restored those comparable with control. In brief, our results showed that PAS-Na may have protective effects on learning and memory against Mn via increasing the number of ChAT-positive neurons and activity of ChAT protein.

Manganese (Mn) is an essential trace element of human. However, excessive Mn can cause manganism. Mn selectively accumulated in Mn-exposed workers' hippocampus which is crucial for higher brain functions such as learning, memory, and motivation during our postnatal life. Studies suggested sodium para-aminosalicylic acid (PAS) appeared to be therapeutic for manganism. We aimed to explore whether PAS could block Mn-induced neuronal injury in hippocampus in vitro. Hippocampal neurons were exposed to 50 μM manganese chloride (MnCl(2)) for 24 h, following by 50, 500, or 5000 μM PAS treatment for 24 h. Cell viability, apoptosis rate, mean fluorescence intensity of mitochondrial and DNA damage were respectively performed. MnCl(2) significantly decreased neurons' viability and fluorescence intensity of comet head of DNA, while increasing the apoptosis rate, mean fluorescence intensity of mitochondrial, percentage of tail DNA, and Olive tail moment of DNA. PAS reduced the percentage of tail DNA and Olive tail moment of Mn-exposed neurons. These data suggested that Mn caused hippocampal neurons' injury, and 50-5000 μM PAS could inhibit Mn-induced DNA damage.

To explore the effects of manganese poisoning on the proliferation of neural stem cells (NSCs) in mice's hippocampus.The mice (weight 8 approximately 10 g) were divided into control group(CG) low-dose group(LDG) middle-dose group(MDG) and high-dose group(HDG)by intraperitoneal injection of 0, 5, 20, 50 mg x kg(-1) x d(-1) of manganese chloride dissolved in physiological saline. The ability of learning and memory was detected by Morris Water Maze, and the proliferation of NSCs in subgranular zone (SGZ) in these mice's hippocampus was also detected by immunohistochemistry.1) Compared with the CG, the ability of learning and memory in all manganism group decreased significantly (P0.01) and this phenomenon in HDG was most notable (P0.01). Meanwhile, the ability of memory was negatively correlated with the dose of manganese chloride (r(s) = -0.598, P0.01), but the difference of swimming speed in every group was of no statistic significance. (2) The numbers of NSCs in proliferation period in SGZ of all manganism groups was much lower than that of CG (P0.01) negatively correlated with the dose of manganese chloride (r(s) = -0.666, P0.01). (3) The reduction of NSCs had a positive correlation to the depression of learning and memory (r(s) = 0.734, P0.01).Manganismus can affect the ability of learning and memory, which is probably caused by the inhalation of manganese on NSCs in hippocampus.

To investigate the distributions of six short-tandem repeat (STR) loci, namely D7S820, D13S317, D16S539, HUMCSF1PO, HUMTPOX and HUMTH01, in Miao minority group at Rongshui county in Guangxi province and construct the relevant genetic database.Sodium-citrated blood specimens were collected from 208 healthy unrelated Miao individuals in Rongshui county. The DNAs from the specimens were extracted with phenol-chloroform method; AmplFSTR Identifier PCR Amplification Kit was used to amplify the extracted DNAs, and 3100 Genetic Analyzer was used to analyze and screen the amplified products.In this study, 7, 8, 6, 7, 5, 7 alleles were observed at the 6 STR loci respectively. The expected distribution of genotype accorded with Hardy-Weinbery equilibrium. The total discrimination power, cumulative paternity exclusion power and total polymorphism information were 0.999995, 0.9959 and 0.9987 respectively.The results demonstrate that these 6 STR loci are of high polymorphism and hereditary stability and are in accord with Mendel's law. The data obtained are valuable in population genetics research, forensic application, and individual identifications.