To study the effect of lysophosphatidic acid (LPA) on the differentiation of embryonic neural stem cells (NSCs) into neuroglial cells in rats in vitro, both oligodendrocytes and astrocytes were detected by their marker proteins galactocerebroside (Gal-C) and glial fibrillary acidic protein (GFAP), respectively, using double-labeling immunocytochemistry. RT-PCR assay was also used for analyzing the expression of LPA receptors in NSCs. Our results showed that: (1) LPA at different concentrations (0.01-3.0 mumol/L) was added to culture medium and cell counting was carried out on the 7th day in all groups. Exposure to LPA led to a dose-dependent increase of oligodendrocytes with the response peaked at 1.0 mumol/L, with an increased percentage of 32.6% (P<0.01) of total cells as compared to that of 8.5% in the vehicle group. (2) LPA showed no effect on the differentiation of NSCs into astrocytes. (3) RT-PCR assay showed that LPA(1) and LPA(3) receptors were strongly expressed while LPA(2) receptor expressed weakly in NSCs. These results suggest that LPA at low concentration might act as an extracellular signal through the receptors in NSCs, mainly LPA(1) and LPA(3) receptors, to promote the differentiation of NSCs into oligodendrocytes, while it exhibits little, if any, conceivable effect on the differentiation of NSCs into astrocytes.
Animals ; Cell Differentiation ; drug effects ; Cells, Cultured ; Lysophospholipids ; pharmacology ; Neural Stem Cells ; cytology ; drug effects ; Neuroglia ; cytology ; Rats ; Receptors, Lysophosphatidic Acid ; metabolism

There are sex differences in some brain areas in mammalians. Parkinson's disease (PD), caused by the mesencephalic substantia nigra (SN) dopaminergic neuronal loss, displays sexual difference, i.e., the incidence is higher and the symptoms are more intense in males than that in females. However, it has not been known whether sexual dimorphisms exist in the SN. Sixty adult Sprague-Dawley rats were randomly divided into 5 groups: (1) Female intact group (F-INT group); (2) Male intact group (M-INT group); (3) Ovariectomized group (OVX group); (4) Castration group (CAST group); (5) Ovariectomized + estrogen-replaced group (OVX-E(2) group): The rats received sequentially physiological dose of estrogen for 3 d from the 7th day after ovariectomization. P50 auditory evoked potential (P50) was recorded for 14 d from electrodes inserted in the rat right SN in quiet and awake state. After recording, the brain tissues were dissected and the tyrosine hydroxylase (TH)-expressing neurons in the compact zone of the SN were counted using immunohistochemical method. The results showed that the number of TH-positive (TH(+)) cells in the SN of normal male animals was less than that in normal female rats (P<0.05), and the T/C ratio of P50 in normal males was significantly less than that in normal females (P<0.01), indicating that there exists sexual difference in function and structure in the SN. No differences in the T/C ratio of P50 or the number of TH(+) cells were found between M-INT and CAST groups. The T/C ratio of P50 and the number of TH(+) cells in the SN in OVX group were reduced significantly compared with those in F-INT group (P<0.01). There was no significant difference in the T/C ratio of P50 and the number of TH(+) cells in the SN between OVX- E(2) and F-INT groups 15-20 d after estrogen replacement, suggesting that estrogen can promote the survival and functional recovery of dopaminergic neurons in the SN. The results suggest that there exist sex-specific differences in the dopaminergic neurons in the SN structurally and functionally. The difference of estrogen level in cerebra between male and female animals may account for the sexual differences. Endogenous estrogen plays an important role in maintaining the integrity and modulating the functional activity of dopamine system in the SN.
Animals ; Dopaminergic Neurons ; cytology ; Estrogens ; pharmacology ; Evoked Potentials, Auditory ; Female ; Male ; Orchiectomy ; Ovariectomy ; Rats ; Rats, Sprague-Dawley ; Sex Characteristics ; Substantia Nigra ; cytology

The present study aimed to investigate whether cannabinoids could modulate the response mediated by ATP receptor (P2X purinoceptor). Whole-cell patch-clamp recording was performed on cultured rat trigeminal ganglionic (TG) neurons. The majority of TG neurons were sensitive to ATP (67/75, 89.33%). Extracellular pretreatment with WIN55212-2, a cannabinoid receptor 1 (CB1 receptor) agonist, reduced ATP-activated current (I(ATP)) significantly. This inhibitory effect was concentration-dependent and was blocked by AM281, a specific CB1 receptor antagonist. Pretreatment with WIN55212-2 at 1×10(-13), 1×10(-12), 1×10(-11), 1×10(-10), 1×10(-9) and 1×10(-8) mol/L reduced I(ATP) (induced by 1×10(-4) mol/L ATP) by (8.14±3.14)%, (20.11±2.72)%, (46.62±3.51)%, (72.16±5.64)%, (80.21±2.80)% and (80.59±3.55)%, respectively. The concentration-response curves for I(ATP) pretreated with and without WIN55212-2 showed that WIN55212-2 shifted the curve downward, and decreased the maximal amplitude of I(ATP) by (58.02±4.21)%. But the threshold value and EC(50) (1.15×10(-4) mol/L vs 1.27×10(-4) mol/L) remained unchanged. The inhibition of I(ATP) by WIN55212-2 was reversed by AM281, suggesting that the inhibition was mediated via the CB1 receptor. Pretreatment with forskolin [an agonist of adenylyl cyclase (AC)] or 8-Br-cAMP reversed the inhibition of I(ATP) by WIN55212-2. These results suggest that the inhibitory effect of cannabinoids on I(ATP) is mediated via the CB1 receptors, that lead to inhibition of the AC-cAMP-PKA signaling pathway.
Adenosine Triphosphate ; physiology ; Animals ; Benzoxazines ; pharmacology ; Cannabinoids ; pharmacology ; Morpholines ; pharmacology ; Naphthalenes ; pharmacology ; Neurons ; drug effects ; physiology ; Patch-Clamp Techniques ; Pyrazoles ; pharmacology ; Rats ; Receptor, Cannabinoid, CB1 ; agonists ; antagonists & inhibitors ; Signal Transduction ; Trigeminal Ganglion ; drug effects ; physiology

It is known that stimulation of the α(2A)-adrenoceptors (α(2A)-ARs) by the selective α(2A)-AR agonist guanfacine produces an important and beneficial influence on prefrontal cortical (PFC) cognitive functions such as spatial working memory and selective attention. However, it is unclear whether stimulation of the α(2A)-ARs has a similar effect on fear conditioning that involves the amygdala and hippocampus. Here, we show that systemically administered guanfacine significantly enhances spatial learning of rats in the Lashley maze: compared with controls, the rats treated with guanfacine required significantly fewer trials and made significantly fewer errors to reach learning criterion. However, guanfacine produced no effect on acquisition of contextual and auditory fear memories. The present study suggests that beneficial effect of α(2A)-AR stimulation is task-dependent: guanfacine improves spatial learning but not fear conditioning.
Adrenergic alpha-2 Receptor Agonists ; pharmacology ; Animals ; Behavior, Animal ; drug effects ; Conditioning (Psychology) ; drug effects ; Fear ; drug effects ; Guanfacine ; pharmacology ; Maze Learning ; drug effects ; Memory ; drug effects ; Rats ; Spatial Behavior ; drug effects

Synapses are inter-neuronal connections that are fundamental working units in neural networks. How synapses are molecularly constructed is a fascinating question, which attracted scientists' attention for many decades. Neuromuscular junction, a field pioneered by Te-Pei FENG and many others, has been an excellent model for studying synaptogenesis and paved the way for our understanding of the synapse formation in the central nervous system. Recent studies shed new light on the molecular mechanisms of central synapse formation by discovering a group of cell adhesion molecules exerting potent synaptogenic effects. This review will focus on those cell adhesion molecules which can induce central synapse formation when expressed in non-neuronal cells.
Cell Adhesion ; Cell Adhesion Molecules ; physiology ; Humans ; Neuromuscular Junction ; physiology ; Synapses ; physiology

The neuromuscular junction (NMJ) has been studied for over a century as a model system for synaptic anatomy, physiology and development. Much of our knowledge of the NMJ has been obtained through imaging techniques, some of which were developed particularly to visualize this synapse's structure and function. In this paper we review the historical development of research on some key aspects of the NMJ, including its structure, nicotinic acetylcholine receptor distribution, the process of synaptic vesicle release, and its development.
Diagnostic Imaging ; Humans ; Neuromuscular Junction ; anatomy & histology ; physiology ; Receptors, Nicotinic ; physiology ; Synaptic Vesicles ; physiology

History, 20th Century ; Physiology ; history

History, 20th Century ; Physiology ; history

Humans ; Myocardial Reperfusion Injury

Since a cyclooxygenase 2 (COX-2) inhibitor can reduce infarct size and improve contractility in ischemic myocardium, the aim of the present study was to explore whether COX-2 inhibitor nimesulide could protect myocardial function against oxidative stress injury in rat hearts, and to investigate the underlying mechanisms. The isolated rat hearts perfused by Langendorff method were exposed to 140 mumol/L of H2O2, and the cardiac contractility was measured. Then, the responses of coronary arteries, precontracted with U-46619, to the endothelium-dependent vasodilator serotonin (5-HT) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were evaluated. The results were as follows: (1) In hearts exposed to H2O2 for 20 min, the left ventricular developed pressure [LVDP, (54.8 +/- 4.0)%] and maximal rate of rise/fall of ventricular pressure [+/-dp/dt(max), (50.8 +/- 3.1)% and (46.2 +/- 2.9) %] were reduced compared with that in the control group (100%). After pretreatment with nimesulide (5 mumol/L) for 10 min before H2O2 perfusion, LVDP and +/-dp/dt(max) were enhanced to (79.9 +/- 2.8)%, (80.3 +/- 2.6)% and (81.4 +/- 2.6)%, respectively (P<0.01), and this was partially abolished by the nitric oxide synthase (NOS) inhibitor L-NAME [(60.2 +/- 2.1)%, (63.9 +/- 2.4)% and (63.1 +/- 2.9)%, respectively, P<0.01]. (2) The vasodilatation induced by 5-HT and SNP in H2O2-treated group was significantly less than that in the control group. Pretreatment with nimesulide for 10 min antagonized the decrease of endothelium-dependent vasodilatation in H2O2-treated group [(-22.2 +/- 4.2) % vs (-6.0 +/- 2.5) %, P<0.01], but had no effect on the decline of endothelium-independent vasodilatation [(-2.0 +/- 1.8)% vs (-7.0 +/- 3.5) %, P>0.05]. (3) Pretreatment with nimesulide for 10 min increased the NO production in H2O2-treated hearts [(2.63 +/- 0.40) vs (1.36 +/- 0.23) nmol/g protein, P<0.05], and this was inhibited by L-NAME. (4) Pretreatment with the selective COX-1 inhibitor piroxicam had no effect on LVDP and +/-dp/dt(max) in isolated hearts exposed to H2O2, but the left ventricular end diastolic pressure (LVEDP) was much higher than that in the group treated with H2O2 alone. Piroxicam did not influence the coronary resistance in H2O2-treated rat hearts. These data suggest that the COX-2 inhibitor nimesulide improves myocardial function in rat hearts suffering from oxidative stress, and this may be through an improvement in endothelium-dependent arterial relaxation and an enhancement of NO production in rat heart.
Animals ; Coronary Vessels ; Cyclooxygenase 2 Inhibitors ; Endothelium, Vascular ; Endothelium-Dependent Relaxing Factors ; Heart ; drug effects ; Hydrogen Peroxide ; Myocardial Reperfusion Injury ; Myocardium ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; metabolism ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Serotonin ; Sulfonamides ; pharmacology ; Vasodilation ; Vasodilator Agents