Aluminum ; toxicity ; Cell Death ; drug effects ; Humans ; Neurons ; drug effects

OBJECTIVETo explore the mechanism of neurotoxicity induced by manganese, and observe the effects on the apoptosis of neurons in rat striatum.

METHODSSD rats were divided into four groups, six rats each group. Three dose groups were exposed to high, middle, and low level of MnCl(2). At the end of experiment, all rats of the exposed groups and control group were decapitated, their striatums were removed and the Mn content of striatum, the apoptotic morphology, ratio and ultrastructural organization were analyzed.

RESULTSThe Mn content of striatum and apoptosis index of the three dose groups exposed to high, middle, and low level of Mn were significantly higher than control group (P < 0.05). The Mn content of striatum of the three dose groups exposed to high, middle, low level of MnCl(2) and control group were 2.98 +/- 0.52, 2.75 +/- 0.37, 2.61 +/- 0.73, 0.60 +/- 0.20 respectively. The apoptosis index of striatum of the three dose groups exposed to high, middle, low level of MnCl(2) and control group were 24.83 +/- 5.98, 17.00 +/- 5.33, 15.33 +/- 2.58, 2.83 +/- 0.41 respectively, and following higher level dose, the apoptosis index increased. The nucleus of neurons in striatum become smaller, condensed, etc, and these character showed apoptosis of neurons.

CONCLUSIONMn can result in apoptotic morphology and increase level of apoptosis in striatum. The level of apoptos varies with Mn concentration.

Animals ; Apoptosis ; drug effects ; Corpus Striatum ; drug effects ; Manganese ; Neurons ; drug effects ; Rats ; Rats, Sprague-Dawley

Animals ; Cocaine ; pharmacology ; Habenula ; drug effects ; physiology ; Neurons ; drug effects ; physiology ; Pain Threshold ; drug effects ; Rats

Action Potentials ; drug effects ; Animals ; Mice ; Mice, Inbred Strains ; Neurons ; drug effects ; physiology ; Plant Extracts ; pharmacology

OBJECTIVETo investigate the protective effect of histone deacetylase inhibitor NL101 on L-homocysteine (HCA)-induced toxicity in rat neurons, and the toxic effect on normal rat neurons.

METHODSIn the presence of NL101 at various concentrations, HCA (5 mmol/L)-induced changes in cell density, necrosis, and viability were determined in the mixed cultures of rat cortical cells and the primary cultures of rat neurons. The direct effect of NL101 on primary neurons was also observed in the absence of HCA. Histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) was used as the control. After the treatments, cell viability, the density, and morphology of neurons and glial cells, and cell necrosis were determined.

RESULTSIn the mixed cultures of cortical cells, NL101 had no effect on HCA (5 mmol/L)-induced cell number reduction at 0.001-10μmol/L; however, it significantly attenuated necrosis at 1-10 μmol/L, and increased neuronal number at 1 μmol/L. NL101 had no effect on the mixed cortical cells in the absence of HCA. In the primary neurons, NL101 reduced neuronal viability and mildly increased necrosis at 1-10 μmol/L in the absence of HCA, while it significantly attenuated HCA-induced neuronal viability reduction at 0.01-10 μmol/L and reduced neuronal necrosis at 1-10 μmol/L. The effects of NL101 were apparently similar to those of SAHA.

CONCLUSIONNL101 has protective effect on HCA-induced neuronal injury but it is neurotoxic at high concentrations, which is similar to the typical histone deacetylase inhibitor SAHA.

Animals ; Cell Survival ; drug effects ; Cells, Cultured ; Histone Deacetylase Inhibitors ; pharmacology ; Neurons ; drug effects ; Rats

AIM AND METHODSTo investigate the effect of 2 mg/kg and 10 mg/kg losartan intraperitoneally (i.p) on arterial blood pressure (AP) and heart rate (HR) in rat and the involvement in the activity of habenulas neurons. Glass micropipette was used to record any changes of unit discharging of neurons in LHb and MHb before and after losartan was intraperitoneally injected.

RESULTSAP and HR were not significantly changed by 2 mg/kg losartan (i.p). However, AP was apparently decreased by 10 mg/kg losartan (i.p), but HR was unchanged. After 10 mg/kg losartan (i.p), 66.66% (12/18) unit discharging of neurons in LHb were increased in frequency, and 61.90% (13/21) in MHb were decreased.

CONCLUSIONAP of rat was significantly decreased by 10 mg/kg losartan (i.p). Depressor effect of losartan (i.p) was involved in the excision of neurons in LHb and the inhibition in MHb.

Animals ; Blood Pressure ; drug effects ; Habenula ; drug effects ; physiology ; Losartan ; pharmacology ; Neurons ; drug effects ; physiology ; Rats ; Rats, Wistar

OBJECTIVETo explore effects of acrylamide on synaptic plasticity of rat neuron and its mechanisms.

METHODS24 Wistar rats were divided into control and test groups randomly, 12 rats in each group. The ratio of male and female in each group was 1:1. Acrylamide (30 mg/kg) was administered to rats by intraperitoneal injection in test group and normal saline (5 g/kg) was given to rats in control group. The neurobehavioral and pathologic changes of heart, liver, spleen, lung and kidney were observed. Changes of parameters in synapse were recorded by electron microscope. As an important target of synapse, change of Synapsin I was measured by immunohistochemical method.

RESULTSCompared with the control group (male: 1.00 ± 0.00; female: 1.00 ± 0.00), the gait score was increased significantly in ACR treated group (male: 2.50 ± 0.55, t = -7.24, P < 0.01; female: 3.17 ± 0.41, t = -12.19, P < 0.01). No obvious pathological changes of heart, liver, spleen, lung and kidney were found in all rats. Compared with the control group (male: (0.41 ± 0.09) µm; female: (0.40 ± 0.06) µm), the length of active zone of synapse was decreased significantly in ACR treated group (male: (0.15 ± 0.05) µm, t = 6.59, P < 0.05; female: (0.14 ± 0.07) µm, t = 7.26, P < 0.05). The width and postsynaptic density of synapse in ACR treated group had no significant difference with control group. The location of Synapsin I of control group and ACR treated group was both in gray matter of spinal dorsal horn. Compared with the control group (male: 195.40 ± 12.30; female: 195.19 ± 6.71), the concentration of Synapsin I was decreased significantly in ACR treated group (male: 60.90 ± 29.19, t = 10.40, P < 0.05; female: 67.56 ± 20.23, t = 15.65, P < 0.05).

CONCLUSIONNeuronal synaptic plasticity was found in damage of nervous system induced by acrylamide in rats, which might be associated with the expression of Synapsin I.

Acrylamide ; toxicity ; Animals ; Female ; Male ; Neuronal Plasticity ; drug effects ; Neurons ; drug effects ; Rats ; Rats, Wistar ; Synapses ; drug effects

OBJECTIVETo investigate the effect of lead-exposed astrocyte conditioned medium (ACM) on the synaptic formation of neurons and to provide reference for the mechanism of lead neurotoxicity.

METHODSAstrocytes were cultured in the medium containing 50, 100, 200, 400, and 800 µmol/L lead acetate for 72 h. Alamar Blue was used to assess the cell viability of astrocytes, and then ACM was collected. Primarily cultured neurons were divided into six groups: pure culture group, non-glutamic acid (Glu)-induced ACM treatment group, Glu-induced lead-free ACM treatment group, and Glu-induced 50, 100, and 200 µmol/L lead acetate-exposed ACM treatment groups. Neurons were collected after being cultured in ACM for 24, 48, or 72 h. The content of synaptophysin (SYP) in neurons was determined by Western blot. The SYP expression in neurons was measured by immunofluorescence after being cultured in ACMfor 72 h.

RESULTSIn all lead-exposed groups, the cell viability of astrocytes declined with increasing concentration of lead (P < 0.05). The Western blot showed that compared with the pure culture group, the non-Glu-induced ACM treatment group and Glu-induced lead- free ACM treatment group had significantly increased content of SYP in neurons (P < 0.01); compared with the non-Glu-induced ACM treatment group, the Glu-induced ACM treatment groups had significantly reduced SYP expression in neurons (P < 0.05); compared with the Glu-induced lead-free ACM treatment group, all lead-exposed ACM treatment groups had the content of SYP in neurons significantly reduced with increasing concentration of lead after 72-h culture (P < 0.01), the 200 µmol/L lead-exposed ACM treatment group had significantly reduced content of SYP in neurons after 48-h culture (P < 0.01), and all lead-exposed ACM treatment groups showed no significant changes in the content of SYP in neurons after 24-h culture. Double-labeling immunofluorescence of SYP showed that all lead-exposed ACM treatment groups had a significant decrease in the number of SYP-fluorescent particles after 72-h culture (P < 0.05).

CONCLUSIONAstrocytes promote synaptic formation of neurons, which may be inhibited during lead exposure.

Astrocytes ; drug effects ; physiology ; Cell Survival ; drug effects ; Cells, Cultured ; Culture Media, Conditioned ; metabolism ; Glutamic Acid ; metabolism ; Lead ; toxicity ; Neurons ; drug effects ; Synapses ; drug effects ; physiology

OBJECTIVEto investigate the effect of deoxypodophyllotoxin (DOP) on membrane potential of dorsal unpaired median neurons (DUM, neurons) and its correlation with sodium channel.

METHODSDUM neurons were labeled with DiBAC4(3). Laser scanning confocal microscope was used to monitor the changes of membrane potential at real time on these neurons that were treated with different concentrations of the DOP. The effect of sodium channel blocker tetrodotoxin (TTX) on the changes was also observed.

RESULTSmembrane potential depolarization induced by the DOP peaked at 5 min and became stabilized after 8min. After compared with fluorescence intensity without treatment, the normalized fluorescence intensity was 69.6 ± 3.0, 72.1 ± 2.7, 77.8 ± 3.6, 86.2 ± 3.1 in cells which were treated with 1, 5, 25, 125 micromol/L DOP, respectively. These numbers were significantly lower than those from untreated control cells (P < 0.01). When DUM neurons were co-incubated with 1 micromol/L TTX for 20 min, then treated with 25 micromol/L DOP, the intensity changed to 63.6 ± 5.4, which was similar to that of the control (P > 0.05). This indicated that the effect of DOP could be completely inhibited by TTX.

CONCLUSIONDOP induced membrane depolarization of DUM neurons in the range of 1 approximately 125 micromol/L and the sodium channel should be involved in this process.

Animals ; Cells, Cultured ; Ganglia, Invertebrate ; drug effects ; physiology ; Membrane Potentials ; drug effects ; physiology ; Neurons ; drug effects ; physiology ; Periplaneta ; drug effects ; physiology ; Podophyllotoxin ; analogs & derivatives ; pharmacology ; Sodium Channels ; metabolism

The effects of administration of motilin into the lateral hypothalamic area (LHA) on gastric antrum motility in conscious rats and on gastric distention (GD) sensitive neurons in dorsal vagal complex (DVC) in anesthetized rats were studied. Microinjection of motilin (0.37 nmol/0.5 microl) into the LHA increased the gastric antrum motility index by 76.29 +/- 4.09% (P<0.01). In 60 GD sensitive neurons, firing rate increased in 39 neurons (65%) and decreased in 21 neurons (35%), which were classified as GD-excitatory and GD-inhibitory neurons, respectively. Firing rate by 7.17 +/- 7.89% within 1.5 min in 15 of 24 GD-excitatory neurons, and firing rate increased by 44.35 +/- 7.89% in 12 of 14 GD-inhibitory neurons after motilin microinjection into the LHA. The results suggest that exogenous motilin in LHA plays a role in the regulation of gastric antrum motility possibly via the vagal pathway from LHA-DVC to the stomach.
Animals ; Hypothalamic Area, Lateral ; drug effects ; Microinjections ; Motilin ; pharmacology ; Neurons ; drug effects ; physiology ; Pyloric Antrum ; drug effects ; physiology ; Rats ; Rats, Wistar ; Vagus Nerve ; drug effects ; physiology