Strychnine (Stry.) has been used, as an instrument for studies of experimental epilepsy, though its precise mode of action has remained obscure. One mechanism of action was partially clarified in 1954 ,by the demonstration that subconvulsive doses of Stry. reduce the amplitude of inhibitory postsynaptic potentials (IPSPs) in the cat's spinal motoneurons (MN). Because of the rapid onset of its action and the absence of effects upon monosynaptic excitatory postsynaptic potentials (EPSPs), it was proposed that Stry. competed with some unidentified transmitter for inhibitory receptor sites on the postsynaptic membrane. Electrophoresis of Stry. is known to block the inhibitory effects of glycine, a likely candidate as an inhibitory transmitter on MN in the cat spinal cord. A Stry. resistant inhibition seems to exist not only in the higher portion of the CNS, but also for the spinal MN. Gamma amino butyric acid (GABA) is a candidate for this synaptic transmitter. In Nembutal anesthetized cat, intracellular recording of spinal MN was performed during Stry. induced seizure. To conclude, it can be said that there were no consistant changes in the MN action potential which would reflect an action of Stry. upon MN's membrane properties important to seizure generation. It is still to be resolved whether the increase in polysynaptic EPSP amplitude is due to a Stry. effect upon the membrane properties of excitatory interneurons or to an effect only upon the inhibitory as well as the EPSPs.
Action Potentials/drug effects* ; Animal ; Cats ; Convulsions/chemically induced ; Female ; Male ; Membrane Potentials/drug effects* ; Motor Neurons/drug effects* ; Spinal Cord/drug effects* ; Strychnine/pharmacology*

The glutamatergic innervations and the GABAergic innervations are respectively the major excitatory and inhibitory inputs of preganglionic cardiac vagal neurons (CVNs). Whether and how these two kinds of innervations interact in the regulation of CVNs is unknown. Using retrograde fluorescent labeling of CVNs and voltage patch-clamp technique, we demonstrated that mixed global application of glutamatergic NMDA and non-NMDA antagonists AP(5) and CNQX, while had no effect on the GABAergic synaptic events of the CVNs in the nucleus ambiguus (NA), significantly decreased the GABAergic synaptic events of the CVNs in the dorsal motor nucleus of the vagus (DMNX). These results suggest that the GABAergic neurons preceding the CVNs in the DMNX receive tonic glutamatergic control, whereas the GABAergic neurons preceding the CVNs in the NA receive little, if any, glutamatergic innervations. This differential central regulation of the CVNs in the DMNX from those in the NA might be a possible mechanism that enables the CVNs in the DMNX play different roles from those in the NA in the parasympathetic control of heart rate and cardiac functions.
Animals ; Animals, Newborn ; Brain Stem ; physiology ; GABAergic Neurons ; physiology ; Glutamates ; physiology ; Heart ; physiology ; Heart Rate ; physiology ; Motor Neurons ; drug effects ; Rats ; Rats, Sprague-Dawley ; Vagus Nerve ; physiology

OBJECTIVETo investigate the effects of nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF) to promoting the sensitive and motor fibres regeneration.

METHODSThirty two Sprague-Dawley rats with 10 mm gap of sciatic nerve were operated and bridged with the new double channel nerve conduit in rhomboid shape. They were randomly divided into two groups, with each in twelve animals. In the first group, 200 micro1 of chitin for medical use was injected into the conduit, and in the second group the two branches of the conduit contained 100 microl of the chitin and 5 microl NGF or CNTF. At twelve and sixteen weeks after the operation, we evaluated the sensitive and motor fibres of regenerative nerve with Holmes, Acetylcholinesterase and Carbonic anhydrase staining.

RESULTSAfter the twelve and sixteen weeks of the operation, there were not significant differences of the regenerative nerve fibres between two channels in the first groups. But in the second group, the number of the motor fibres of the regenerative nerve of CNTF branch channel was much more and distributed better than the others, while the number and density of sensitive fibres was inferior to NGF. The latency of compound muscle active potential and cortical somatosensory evoked potential of the nerve in the CNTF branch was shorter than the one in the NGF branch, but its amplitude was higher.

CONCLUSIONSThe CNTF could significantly promote the regeneration of motor fibres and the NGF could promote better for the regeneration of sensitive fibres.

Animals ; Ciliary Neurotrophic Factor ; pharmacology ; Female ; Male ; Motor Neurons ; Nerve Growth Factor ; pharmacology ; Nerve Regeneration ; drug effects ; Neurons, Afferent ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effects of low-dose chlorpyrifos (CPF) exposure on dopaminergic (DA) neurons in the midbrain substantia nigra and neural behavioral development in neonatal rats.

METHODSPostnatal 11 day old Sprague-Dawley rats were randomly assigned into CPF, menstruum dimethysulfoxide (DMSO) and normal saline (NS) groups. The rats in the CPF group were injected with low-dose CPF (5 mg/kg?d) on postnatal days 11-14. The two control groups were injected with DMSO or NS respectively. The rats were sacrificed on postnatal days 15, 20, 30, and 60. Body weight gain, outward appearance of brain tissue, the coefficient of brain and the water content of brain tissue were measured. Tyrosine hydroxylase (TH) expression in DA neurons in the midbrain substantial nigra was examined by immunohistochemical straining. Immune electron microscopy was used to examine the subcellular structure of DA neurons. Open field test, grip strength test, slope test and Morris water maze test were used to examine the neurobehavioral changes.

RESULTSThe outward appearance of brain tissue was normal in the three groups. There were no significant differences in the absolute value of body weight gain, the coefficient of brain and the water content of brain tissue among the three groups. CPF exposure decreased the level of TH immunoreactivity (P<0.05) in the substantia nigra of CPF group since postnatal day 30 compared with the DMSO and NS groups. The subcellular structures of some DA neurons in the CPF group were impaired. Decreased motor activity and learning and memory impairments were observed in the CPF group compared with those in the DMSO and NS groups (P<0.05) since postnatal day 30.

CONCLUSIONSCPF exposure during the neonatal period can cause long-term motor activity and learning and memory impairments in accompany with DA neurons damage in the midbrain substantia nigra.

Animals ; Animals, Newborn ; Behavior, Animal ; drug effects ; Chlorpyrifos ; toxicity ; Dopaminergic Neurons ; drug effects ; Female ; Insecticides ; toxicity ; Learning ; drug effects ; Male ; Motor Activity ; drug effects ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; drug effects

Animals ; Embryo Culture Techniques ; Embryo, Mammalian ; Female ; Ganglia, Spinal ; cytology ; drug effects ; Glial Cell Line-Derived Neurotrophic Factor ; pharmacology ; Male ; Motor Neurons ; drug effects ; Neurons, Afferent ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effect of 2,5-hexanedione (2,5-HD) on the levels of nerve growth factor (NGF) in sciatic nerve of rats and motor-neurons.

METHODA total of 50 Wistar rats were randomly designed into five groups and intoxicated with 400 mgxkg(-1)xd(-1) 2,5-HD for 0, 7, 14, 21, 28 d. Immunohistochemistry and real-time PCR were used to detect the levels of NGF and NGF mRNA. Motor neuron VSC4.1 cells were administrated with 0, 2.5, 5.0, 10.0, 20.0 mmol/L 2,5-HD for 24 h and 10.0 mmol/L 2,5-HD was chosen to intoxicated VSC4.1 cells for 0, 1, 3, 6, 12, 24, 48 h respectively. Immunofluorescence technique was selected to detect the levels of NGF.

RESULTSThe NGF level in sciatic nerve of rats administrated with 400 mgxkg(-1)xd(-1) 2,5-HD showed increase tendency at begin and then decrease after exposure. The NGF mRNA level in 14 d (2(-DeltaDeltaCt)= 3.46), 21 d (2(-DeltaDeltaCt)= 5.28) and 28 d (2(-DeltaDeltaCt)= 3.10) were higher than those in 0 d (2(-DeltaDeltaCt)= 1) and 7 d (2(-DeltaDeltaCt)= 0.78). In vitro tests of VSC4.1 cells showed that NGF levels in 5.0 mmol/L (43.24 +/- 7.52), 10.0 mmol/L (43.48 +/- 10.86) and 20.0 mmol/L (63.13 +/- 10.68) were higher than those in 0 mmol/L (16.32 +/- 4.20)(q values were 19.92, 19.72, 32.78, respectively, P < 0.01) and 2.5 mmol/L (19.78 +/- 2.66) (q values were 17.50, 17.42, 30.63, respectively, P < 0.01) in 24 h and the NGF level in 20.0 mmol/L was higher than those in 5.0 mmol/L (q = 13.04, P < 0.01) and 10.0 mmol/L (q = 11.71, P < 0.01). The NGF levels of VSC4.1 cells with 10.0 mmol/L 2,5-HD in 6 h (18.66 +/- 2.89), 12 h (23.14 +/- 6.08), 24 h (27.66 +/- 6.11) and 48 h (17.25 +/- 3.05) were increased compared with that in 0 h (10.18 +/- 1.81) (q values were 9.64, 15.74, 21.76, 8.50, respectively, P < 0.01), 1 h (9.31 +/- 1.28) (q values were 10.28, 16.17, 21.95, 9.20, respectively, P < 0.01) and 3 h (10.44 +/- 2.13) (q values were 9.25, 15.24, 21.17, 8.10, respectively, P < 0.01), and NGF levels in 12 h and 24 h increased compared with those in 6 h (q values were 5.24, 10.77, respectively, P < 0.01) and 48 h (q values were 7.31, 13.26, respectively, P < 0.01).

CONCLUSION2,5-HD could increase NGF levels in sciatic nerve of rats and motor-neurons, and the dose or time dependent effects were observed in this study.

Animals ; Cell Line ; Hexanones ; toxicity ; Male ; Motor Neurons ; drug effects ; metabolism ; Nerve Growth Factor ; metabolism ; Rats ; Rats, Wistar ; Sciatic Nerve ; drug effects ; metabolism

AIMTo investigate the effects of melatonin (MT) on histology and behavioral tests during global cerebral ischemia-reperfusion in gerbils.

METHODSGlobal cerebral ischemia was induced by occluding the bilateral common carotid arteries for 10 min in gerbils. Three doses of MT were administrated intraperitoneally 30 min prior to the onset of ischemia. Locomotor activity was measured by using the open field method 3 and 7 days after the ischemic episode. T maze test was carried out 4, 5 and 6 days after ischemia to assess the working memory of gerbils. Neuronal damage was assessed in CA1 pyramidal layer of gerbil hippocampus and evaluated 7 days after ischemia.

RESULTSMT significantly reversed the locomotor activity increases, ameliorated learning and working memory deficit, and reduced the extent of CA1 hippocampal pyramidal cells injury after transient global cerebral ischemia in the Mongolian gerbil.

CONCLUSIONMT provides significantly protective effect against both histological and behavioral consequences of global cerebral ischemia-reperfusion injury in gerbils.

Animals ; Brain Ischemia ; complications ; Female ; Gerbillinae ; Hippocampus ; drug effects ; pathology ; Learning ; drug effects ; Male ; Melatonin ; pharmacology ; therapeutic use ; Memory ; drug effects ; Motor Activity ; drug effects ; Neurons ; pathology ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Random Allocation ; Reperfusion Injury ; etiology ; physiopathology ; prevention & control

OBJECTIVETo study the effect of testosterone propionate (TP) on the distribution pattern of calcitonin gene-related peptide (CGRP) in two types of motoneuron (Mn) pools in rats.

METHODThe double labeling of cholera toxin B subunit coupled with colloidal gold (CB-Au) retrograde identification combining with immunocytochemistry was mainly used to reveal the distribution pattern of CGRP-like immunoreactivity (CGRP-LI) and its changes in the motoneuron pools labeled by CB-Au.

RESULTTP injected intramuscularly 28 days later significantly decreased CGRP expression in Mn pool innervating extensor digitorum longus (EDL, fast-twitch), comparing with corresponding control and castration group respectively (P < 0.001), while no significant effect on Mn pools innervating soleus (SOL, slow-twitch, P > 0.05) was observed.

CONCLUSIONEDL-Mn pool is more sensitive to testosterone propionate than SOL-Mn pool in regulating CGRP expression.

Animals ; Calcitonin Gene-Related Peptide ; drug effects ; metabolism ; Male ; Motor Neurons ; drug effects ; metabolism ; Muscle Fibers, Fast-Twitch ; cytology ; drug effects ; Muscle Fibers, Slow-Twitch ; cytology ; drug effects ; Rats ; Rats, Wistar ; Testosterone Propionate ; pharmacology

OBJECTIVETo explore the mechanism of cytotoxic effect of 2, 5-hexanedione (2, 5-HD) on motor neuron.

METHODSVsc4.1 (a cell line from motor neuron) was incubated with a series concentration of 2, 5-HD. The cell viability, Ca(2+) Mg(2+) ATPase and Na(+)K(+) ATPase were detected. Laser scanning confocal microscope (LSCM) was used for detecting intracellular calcium level. The average calcium level in VSC4.1 was measured by flow cytometry.

RESULTSThe cell viability was decreased when Vsc4.1 cells were treated with 2, 5-HD at the dosage of 2.5, 5.0, 7.5, 10, 15 and 20 mmol/L for 24 hours. Compared with the control group the activity of Ca(2+) Mg(2+) ATPase was decreased to 70.02%, 77.44% and 47.47% respectively; the activity of Na(+)K(+) ATPase was decreased to 82.07%, 72.45% and 50.71%. The difference was significant. Intracellular free calcium of VSC4.1 cell was increased rapidly within 10 s and then recovered within 40 seconds when it was exposed to 33.5 mmol/L 2, 5-HD. An increase in intracellular calcium was observed when the VSC4.1 was treated with 33.5 mmol/L 2, 5-HD. The peak of intracellular calcium level occurred ten minutes later.

CONCLUSIONThe disturbance of calcium homeostasis may be involved in the mechanisms of neurotoxicity of 2, 5-HD.

Animals ; Ca(2+) Mg(2+)-ATPase ; metabolism ; Calcium ; metabolism ; Cell Line ; Dose-Response Relationship, Drug ; Hexanones ; toxicity ; Motor Neurons ; drug effects ; metabolism ; Rats ; Sodium-Potassium-Exchanging ATPase ; metabolism

OBJECTIVETo study the relationship between the protection of Ginsenoside(GS) for spinal cells and nitric oxide (NO).

METHODSpinal cells were cultured in vitro, the model of peripheral nerve was established by scarifying the cells, and NO was measured by Griess method.

RESULTNO in injury group was high than that in noninjury group and NO in group cultured by GS was less than that in group cultured by common medium.

CONCLUSIONNO increases when peripheral nerve is injuried, and the protective effect of GS on spinal cells may be through inhibiting NO release.

Animals ; Cells, Cultured ; Fetus ; Ginsenosides ; isolation & purification ; pharmacology ; Motor Neurons ; cytology ; drug effects ; metabolism ; Neurons, Afferent ; cytology ; drug effects ; metabolism ; Neuroprotective Agents ; pharmacology ; Nitric Oxide ; metabolism ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; cytology ; metabolism