ABSTRACT
In addition to classical synaptic transmission, information is transmitted between cells via the activation of extrasynaptic receptors that generate persistent tonic current in the brain. While growing evidence supports the presence of tonic NMDA current (INMDA) generated by extrasynaptic NMDA receptors (eNMDARs), the functional significance of tonic I(NMDA) in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate I(NMDA) facilitates the α-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptor (AMPAR)-mediated steady-state current in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs). In low-Mg2+ artificial cerebrospinal fluid (aCSF), glutamate induced an inward shift in I(holding) (I(GLU)) at a holding potential (V(holding)) of -70 mV which was partly blocked by an AMPAR antagonist, NBQX. NBQX-sensitive I(GLU) was observed even in normal aCSF at V(holding) of -40 mV or -20 mV. I(GLU) was completely abolished by pretreatment with an NMDAR blocker, AP5, under all tested conditions. AMPA induced a reproducible inward shift in I(holding) (I(AMPA)) in SON MNCs. Pretreatment with AP5 attenuated I(AMPA) amplitudes to ~60% of the control levels in low-Mg2+ aCSF, but not in normal aCSF at V(holding) of -70 mV. I(AMPA) attenuation by AP5 was also prominent in normal aCSF at depolarized holding potentials. Memantine, an eNMDAR blocker, mimicked the AP5-induced I(AMPA) attenuation in SON MNCs. Finally, chronic dehydration did not affect I(AMPA) attenuation by AP5 in the neurons. These results suggest that tonic I(NMDA), mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs.
Subject(s)
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid , Brain , Cerebrospinal Fluid , Dehydration , Glutamic Acid , Memantine , N-Methylaspartate , Neurons , Receptors, AMPA , Receptors, N-Methyl-D-Aspartate , Supraoptic Nucleus , Synaptic TransmissionABSTRACT
The present study was aimed to explore the effects of intraperitoneal injection of growth hormone releasing peptide-6 (GHRP-6), a ghrelin receptor agonist, on food intake and neuronal activity of feeding-related nuclei in the hypothalamus of NMRI mice. Accumulated amount of food intake was measured, and total number of c-fos immunoreactive neurons in arcuate nucleus (ARC), paraventricular nucleus (PVN) and supraoptic nucleus (SON) was counted by immunohistochemistry at 1, 3 and 6 h after the GHRP-6 injection. The results showed that GHRP-6 significantly increased the amount of food intake with a peak at 3 h after the GHRP-6 injection. Meanwhile, GHRP-6 could promote c-fos expression in the ARC and PVN independent of food intake, and the total number of c-fos immunoreactive neurons was peaked at 1 h after injection and then decreased gradually. These results suggest that GHRP-6 may increase food intake in time-dependent manner, which is associated with up-regulations of c-fos protein expression in the ARC and PVN.
Subject(s)
Animals , Male , Mice , Arcuate Nucleus of Hypothalamus , Eating , Immunohistochemistry , Neurons , Oligopeptides , Paraventricular Hypothalamic Nucleus , Proto-Oncogene Proteins c-fos , Receptors, Ghrelin , Supraoptic NucleusABSTRACT
The present study was designed to investigate the inhibitory effects of intravenous general anesthetic propofol (0.1-3.0 mmol/L) on excitatory synaptic transmission in supraoptic nucleus (SON) neurons of rats, and to explore the underlying mechanisms by using intracellular recording technique and hypothalamic slice preparation. It was observed that stimulation of the dorsolateral region of SON could elicit the postsynaptic potentials (PSPs) in SON neurons. Of the 8 tested SON neurons, the PSPs of 7 (88%, 7/8) neurons were decreased by propofol in a concentration-dependent manner, in terms of the PSPs' amplitude (P < 0.01), area under curve, duration, half-width and 10%-90% decay time (P < 0.05). The PSPs were completely and reversibly abolished by 1.0 mmol/L propofol at 2 out of 7 tested cells. The depolarization responses induced by pressure ejection of exogenous glutamate were reversibly and concentration-dependently decreased by bath application of propofol. The PSPs and glutamate-induced responses recorded simultaneously were reversibly and concentration-dependently decreased by propofol, but 0.3 mmol/L propofol only abolished PSPs. The excitatory postsynaptic potentials (EPSPs) of 7 cells increased in the condition of picrotoxin (30 µmol/L, a GABA(A) receptor antagonist) pretreatment. On this basis, the inhibitory effects of propofol on EPSPs were decreased. These data indicate that the presynaptic and postsynaptic mechanisms may be both involved in the inhibitory effects of propofol on excitatory synaptic transmission in SON neurons. The inhibitory effects of propofol on excitatory synaptic transmission of SON neurons may be related to the activation of GABA(A) receptors, but at a high concentration, propofol may also act directly on glutamate receptors.
Subject(s)
Animals , Rats , Anesthetics, Intravenous , Pharmacology , Excitatory Postsynaptic Potentials , GABA-A Receptor Antagonists , Pharmacology , Glutamic Acid , Pharmacology , In Vitro Techniques , Neurons , Propofol , Pharmacology , Receptors, Glutamate , Metabolism , Supraoptic Nucleus , Cell BiologyABSTRACT
Physiological evidence indicates that the supraoptic nucleus (SON) is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs) responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1) the intrinsic membrane properties of the MNCs themselves and 2) synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO) may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON.
Subject(s)
Animals , Humans , Rats , Neurons/physiology , Neurosecretory Systems/physiology , Nitric Oxide/physiology , Oxytocin , Supraoptic Nucleus/physiology , Vasopressins , Action Potentials/physiology , Guanylate Cyclase/metabolism , Nitric Oxide Donors/pharmacology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Water-Electrolyte Balance/physiologyABSTRACT
The purpose of this study is to investigate the antinociceptive effects of ginsenosides on toothache. c-Fos immunoreactive (IR) neurons were examined after noxious intrapulpal stimulation (NS) by intrapulpal injection of 2 M KCl into upper and lower incisor pulps exposed by bone cutter in Sprague Dawley rats. The number of Fos-IR neurons was increased in the trigeminal subnucleus caudalis (Vc) and the transitional region between Vc and subnucleus interpolaris (Vi) by NS to tooth. The intradental NS raised arterial blood pressure (BP) and heart rate (HR). The number of Fos-IR neurons was also enhanced in thalamic ventral posteromedial nucleus (VPMN) and centrolateral nucleus (CLN) by NS to tooth. The intradental NS increased the number of Fos-IR neurons in the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN), central cardiovascular regulation centers. Ginsenosides reduced the number of c-Fos-IR increased by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Naloxone, an opioid antagonist, did not block the effect of ginsenoside on the number of Fos-IR neurons enhanced by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Ginsenosides ameliorated arterial BP and HR raised by NS to tooth and reduced the number of Fos-IR neurons increased by NS to tooth in the NTS, RVLM, hypothalamic SON, and PVN. These results suggest that ginsenosides have an antinociceptive effect on toothache through non-opioid system and attenuates BP and HR increased by NS to tooth.
Subject(s)
Animals , Rats , Arterial Pressure , Brain , Ginsenosides , Heart Rate , Incisor , Naloxone , Neurons , Paraventricular Hypothalamic Nucleus , Rats, Sprague-Dawley , Solitary Nucleus , Supraoptic Nucleus , Tooth , Toothache , Ventral Thalamic NucleiABSTRACT
Arginine vasopressin (AVP) is a neuropeptide with vasoconstrictive, antidiuretic, cardiovascular regulative and hepatic glycogenolysis effects, that also affects other behaviors including modulating learning. A number of studies on AVP regulation have been conducted in various metabolic diseases (disorders). In this study, the immunoreactivities of AVP in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) and mRNA expressions in the hypothalamus were investigated by immunohistochemistry and quantitative real-time PCR (RT-qPCR) in stroke-prone spontaneously hypertensive rats at different ages (i.e., at postnatal months [PM] 1, 8, and 12). Blood glucose levels in the PM 8 group were higher than in the other groups. However, cresyl violet positive neurons were detected in the PVN and SON of all animals, and numbers of cresyl violet positive neurons were similar in all aged groups. In addition, AVP immunoreactivity was detected in the PVN and SON of all age groups, and AVP immunoreactivity and mRNA expression levels were found to be increased in proportion to age by immunohistochemistry and RT-qPCR. These results suggest that the diabetic condition is temporally generated after hypertension has developed. Furthermore, our findings suggest that increased AVP expressions in the hypothalamic PVN and SON are associated with hypertension by age.
Subject(s)
Aged , Animals , Humans , Arginine , Arginine Vasopressin , Benzoxazines , Blood Glucose , Glycogenolysis , Hypertension , Hypothalamus , Immunohistochemistry , Learning , Metabolic Diseases , Molybdenum , Neurons , Neuropeptides , Oxides , Paraventricular Hypothalamic Nucleus , Rats, Inbred SHR , Real-Time Polymerase Chain Reaction , RNA, Messenger , Supraoptic Nucleus , ViolaABSTRACT
To investigate the effects of novel intravenous general anesthetic propofol on membrane electrophysiological characteristics and action potential (AP) of the supraoptic nucleus (SON) neurons and possible ionic mechanisms, intracellular recordings were conducted in SON neurons from the coronal hypothalamic slice preparation of adult male Sprague Dawley (SD) rats. The results showed that bath application of 0.1 mmol/L propofol induced a significant decline in resting potential (P < 0.01), and higher concentrations of propofol (0.3 and 1.0 mmol/L) decreased time constant and slope resistance of cell membrane (P < 0.01). Under the hyperpolarizing current pulses exceeding 0.5 nA, an anomalous rectification was induced by hyperpolarization-activated cation channel (I(h) channel) in 11 out of 18 tested SON neurons. Bath of propofol reversibly decreased the anomalous rectification. Moreover, 0.1 mmol/L propofol elevated threshold level (P < 0.01) and decreased Max L. slope (P < 0.05) of the spike potential in SON neurons. Interestingly, 0.3 and 1.0 mmol/L propofol nullified APs in 6% (1/18) and 71% (12/17) tested SON neurons, respectively. In the SON neurons where APs were not nullified, propofol (0.3 mmol/L) decreased the amplitude of spike potential (P < 0.05). The higher concentrations of propofol (0.3 and 1.0 mmol/L) decreased firing frequencies evoked by depolarizing current pulses (0.1-0.7 nA), and shifted the current intensity-firing frequency relation curves downward and to the right. These results suggest that propofol decreases the excitability of SON neurons by inhibiting I(h) and sodium channels.
Subject(s)
Animals , Male , Rats , Action Potentials , Anesthetics, Intravenous , Pharmacology , Cyclic Nucleotide-Gated Cation Channels , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels , Hypothalamus , Physiology , In Vitro Techniques , Potassium Channels , Propofol , Pharmacology , Rats, Sprague-Dawley , Sodium Channel Blockers , Pharmacology , Supraoptic Nucleus , PhysiologyABSTRACT
BDNF belongs to the neurotrophin family and important molecular mediator of functional and structural plasticity. The highest levels of BDNF are found in the hippocampus and hypothalamus of the adult rat. Hypothalamus is important because of its high degree of plasticity, but little is known about distribution of BDNF in hypothalamic nuclei. Therefore, it is necessary to study distribution and expression pattern of BDNF in each hypothalamic nuclei to understand changes of BDNF through various neural damages including spinal cord injury. Through this experiment, we found specific BDNF expression pattern in some regions of hypothalamus and the results are as follows. 1) BDNF expressions were found in median eminence, arcuate nucleus, supraoptic nucleus, and periventricular nucleus of rat hypothalamus. 2) BDNF immunoreactive cells and nerve fibers were of various shapes and sizes. 3) Glial cells also express BDNF in certain hypothalamic nuclei. These results seem to be useful for future investigations of neurochemical changes in the hypothalamus induced by various neural trauma or degenerative changes
Subject(s)
Adult , Animals , Humans , Rats , Arcuate Nucleus of Hypothalamus , Brain-Derived Neurotrophic Factor , Hippocampus , Hypothalamus , Median Eminence , Nerve Fibers , Neuroglia , Plastics , Spinal Cord Injuries , Supraoptic NucleusABSTRACT
In the present study, we performed immunohistochemical studies to investigate the detailed distribution of insulin-like growth factor binding protein 7 (IGFBP7) in the central nervous system of adult rats. Twelve adult (4~6 month old) Sprague-Dawley rats were examined in this study. Immunohistochemistry using specific antibodies against IGFBP7 was performed in accordance with the free-floating method. In the present study, IGFBP7 immunoreactivity was observed in the cerebral cortex, hippocampus, brainstem, cerebellum and spinal cord. In the cerebral cortex, heavily stained neurons were seen in layers II-VI. In the hippocampus, pyramidal cells in CA1-3 region were strongly immunoreactive for IGFBP7. Strong immunoreactive neurons were also found in the supraoptic nucleus, paraventricular nucleus, periaqueductal gray and oculomotor nucleus. In the cerebellum, IGFBP7 immunoreactivity was prominent in the Purkinje cells and cerebellar output neurons. IGFBP7-immunoreactive neurons were prominent in the superior vestibular nucleus, cochlear nucleus, trigeminal motor nucleus, nucleus of the trapezoid, and facial nucleus. IGFBP7-immunoreactive neurons were also observed mainly in the anterior horn of the spinal cord. The first demonstration of IGFBP7 localization in the whole brain may provide useful data for the future investigations on the structural and functional properties of IGFBP7.
Subject(s)
Adult , Animals , Humans , Rats , Antibodies , Brain , Brain Stem , Carrier Proteins , Central Nervous System , Cerebellum , Cerebral Cortex , Cochlear Nucleus , Hippocampus , Horns , Immunohistochemistry , Neurons , Paraventricular Hypothalamic Nucleus , Periaqueductal Gray , Purkinje Cells , Pyramidal Cells , Rats, Sprague-Dawley , Spinal Cord , Supraoptic Nucleus , Trigeminal NucleiABSTRACT
<p><b>OBJECTIVE</b>To study the changes in the plasticity of the neurons and astrocytes in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus of rats exposed to a humid and hot environment.</p><p><b>METHODS</b>The rats were subjected to stimulation with a humid and hot environment for 120 min in a climate chamber (dry bulb temperature of 40.0-/+0.5 degrees C with relative humidity of 60-/+5%). During the exposure, the behavioral responses of the rats were observed, and the changes in the expressions of Fos and GFAP in the PVN and SON in response to the exposure evaluated using immunohistochemical ABC methods.</p><p><b>RESULTS</b>Exposure to a humid and hot environment caused restlessness and agitation in the rats, which showed increased respiratory frequency and scratching of the face with the forelimbs. Two rats died after the 120-min exposure. Significantly increased expressions of Fos and GFAP were detected in the PVN and SON following the exposure as compared with the control group.</p><p><b>CONCLUSION</b>The neurons and astrocytes in the PVN and SON both participate in the regulation of responses to exposure to a humid and hot environment.</p>
Subject(s)
Animals , Male , Rats , Astrocytes , Cell Biology , Physiology , Glial Fibrillary Acidic Protein , Hot Temperature , Humidity , Hypothalamus , Cell Biology , Metabolism , Immunohistochemistry , Neuronal Plasticity , Physiology , Neurons , Cell Biology , Physiology , Oncogene Proteins v-fos , Paraventricular Hypothalamic Nucleus , Cell Biology , Metabolism , Random Allocation , Rats, Sprague-Dawley , Supraoptic Nucleus , Cell Biology , MetabolismABSTRACT
The role of neuropeptides in the central nervous system (CNS) has received increasing attention. Numerous peptide molecules are found in the mammalian CNS and many of them are thought to act as either neurotransmitters or neuromodulators. The neuropeptides found in high concentration in the hypothalamus include vasopressin (VP), vasoactive intestinal polypeptide, somatostatin, and oxytocin. The main approches to assess the involvement of neuropeptides can be focused on functions affecting the aging of the brain. Morphological aging of the CNS has been characterized by degenerative changes of fiber connections and cell loss, although degeneration does not always occur to the same extent throughout various parts of the brain and, moreover, varies for different cell types. Despite of many studies in VP containing neurons , there exist discrepancies in results about the changes of aged rat brain. The aim of the present study is, therefore, to investigative possible changes in the number and morphology of VPimmunoreactive neurons with aging in each area of the hypothalmus of the aged rats. As a result, the number of VP-immunoreactive neurons was decreased in hypothalamus nucleus of aged group. Especially, in VP-immunoreactive neurons of hypothalamus, the size of neuronal cell body and nuclei in aged group is larger than in young group and the fiber density of immunoreactivity neurons of median eminance (ME) in aged group is stronger than in young group. But, the total number of VP-immunoreactive neurons in the suprachiasmatic nucleus (SCN) of the aged group is larger than in the young group. These studies indicate the involvement of VP-immunoreactive neurons in aging process of hypothalamus, and aging process may affect the synthesis of VP in the neurons of hypothalamic nuclei. Whereas, in VP expression, aging process induces an enlargement of the cell size of surviving neurons to compensate.
Subject(s)
Animals , Rats , Aging , Brain , Cell Size , Central Nervous System , Hypothalamus , Neurons , Neuropeptides , Neurotransmitter Agents , Oxytocin , Paraventricular Hypothalamic Nucleus , Somatostatin , Suprachiasmatic Nucleus , Supraoptic Nucleus , Vasoactive Intestinal Peptide , VasopressinsABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of motilin-immunoreactive neurons in the hypothalamus and the effect of central administration of erythromycin (EM) on the regulation of gastric motility in diabetic rats.</p><p><b>METHODS</b>The motilin immunoreactive neurons in the hypothalamus and the hippocampus were detected by immunohistochemistry with rabbit anti-motilin polyclonal antibody. To measure the gastric motility, force transducers were surgically affixed to the gastric serosa. A microinjection syringe was connected via a plastic tube to an injection cannula, which was connected with a stainless steel guide cannula. The syringe was inserted into the right lateral cerebral ventricle for microinjecting the chemicals.</p><p><b>RESULTS</b>Diabetic mellitus was successfully induced in cohorts of rats. Motilin-immunoreactive neurons significantly increased in the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus in the diabetic rats. Intracerebroventricular (i.c.v.) administration of EM, a motilin receptor agonist, stimulated the gastric motility of diabetic rats. EM (91.56 nmol, i.c.v.) dose-dependently increased the amplitude by (174.82 +/- 48.62)% (P<0.05), and increased the frequency by (70.43 +/- 27.11)% (P < 0.05) in 5 min. The stimulatory effect lasted more than 15 min to the end of the measurement, and can be blocked partially by the prior treatment of motilin receptor antagonist GM-109.</p><p><b>CONCLUSION</b>Motilin-immunoreactive neurons are increased in the PVN and SON of the hypothalamus in diabetic rats. Centrally administered EM may regulate gastric motility by binding to the central motilin receptors, and central motilin might be involved in regulation of gastric motility in diabetic rats.</p>
Subject(s)
Animals , Male , Rats , Diabetes Mellitus, Experimental , Metabolism , Dose-Response Relationship, Drug , Erythromycin , Pharmacology , Gastrointestinal Agents , Pharmacology , Gastrointestinal Motility , Physiology , Hippocampus , Cell Biology , Metabolism , Injections, Intraventricular , Microinjections , Motilin , Metabolism , Neurons , Cell Biology , Metabolism , Paraventricular Hypothalamic Nucleus , Cell Biology , Metabolism , Rats, Sprague-Dawley , Receptors, Gastrointestinal Hormone , Receptors, Neuropeptide , Statistics, Nonparametric , Supraoptic Nucleus , Cell Biology , MetabolismABSTRACT
Na(+)-Ca(2+) exchanger plays a fundamental role in controlling the changes in intracellular concentration of Na(+) and Ca(2+) ions. Two different families of Na(+)-Ca(2+) exchanger, NCX (K(+)-independent Na(+)-Ca(2+) exchanger) and NCKX (K+-dependent Na(+)-Ca(2+) exchanger), are known and each family includes several isoforms. But little is known about their expression in pituitary gland. In this study, in situ hybridization with digoxigeninlabeled riboprobe and double-labeled experiments with immunohistochemistry were applied to investigate the expression of NCX and NCKX mRNAs and their distribution in normal rat pituitary gland. NCX2 mRNA hybridization signals were expressed in pars distalis, while both NCX2 and NCKX2 mRNAs expression were strongly observed in pars nervosa. NCX2 and NCKX2 mRNA were also expressed in supraoptic nucleus of hypothalamus. In pars distalis, 68.2% of growth hormone secreting cells was colocalized with NCX2 mRNA, whereas NCX2 mRNA was not found in S100 positive folliculostellate cells. These results suggest that NCX2 in pars distalis and NCX2 and NCKX2 in pars nervosa appear to be involved in endocrine function of pituitary gland.
Subject(s)
Animals , Humans , Rats , Growth Hormone , Hypothalamus , Immunohistochemistry , In Situ Hybridization , Ions , Pituitary Gland , Protein Isoforms , RNA, Messenger , Sodium-Calcium Exchanger , Supraoptic NucleusABSTRACT
Chronic alcohol intake can profoundly modify the neuronal activity and the morphologic structure of hypothalamic nucleus in the rat brain. The aim of the present study is to observe the effects of chronic alcohol intake on expression of vasopressin and oxytocin in the paraventricular and supraoptic nucleus in the rat hypothalamus. Experimental rats (n=14) were divided into control group and chronic alcohol group. Chronic alcohol group was induced via daily liquid alcohol intake for 6 months beginning at 8 weeks of age. As a result, the number of vasopressin and oxytocin-containing neurons was decreased in the paraventricular and supraoptic nucleus in chronic alcohol group. Especially, the number of vasopressin-containing neurons of chronic alcohol group was significantly decreased in the paraventricular nucleus. Chronic alcohol intake produced significant changes in the volume of the cell bodies and their nucleus in neurons of the paraventricular and supraoptic nucleus. Particularly, the size of nucleus of vasopressin-containing neurons in chronic alcohol group was larger than in control group. These results show that chronic alcohol intake may affect the synthesis of vasopressin and oxytocin in the neurons of hypothalamic nuclei. Whereas, chronic alcohol intake induces an enlargement of the cell size of surviving neuron to compensate.
Subject(s)
Animals , Rats , Brain , Cell Size , Hypothalamus , Neurons , Oxytocin , Paraventricular Hypothalamic Nucleus , Supraoptic Nucleus , VasopressinsABSTRACT
<p><b>OBJECTIVE</b>To study the rules of protein expression of proto-oncogene (c-Fos/c-Jun) in different brain areas and nucleus of psychological stressed mice and the regulatory effect of modified Xiaoyao Pill (SXP).</p><p><b>METHODS</b>The mouse psychological stress model was established by electrical stimulation; SXP was administrated at the dose of 2 mg/g; the protein expression of c-Fos and c-Jun in different brain areas and nucleus, including hippocampus (CA1-4), central amygdaloid nucleus (CAN), paraventricular nucleus (PVN) and supraoptic nucleus (SON), were detected by immunohistochemical method.</p><p><b>RESULTS</b>The protein expressions of c-Fos and c-Jun in all the tested brain areas of model mice 3 h after being stressed for 1, 3 or 5 times, were significantly higher than those of the normal mice (P < 0.01); After being stressed for one time, the expression at 1 h after stimulation was lower than that at 3 h after stimulation (P < 0.05), the expression in mice treated with SXP was lower than that in the untreated group, 3 h after three or five times of stress (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>The protein expression of c-Fos and c-Jun began to rise 1 h after psychological stress and reached the peak at the 3rd h. That of c-Fos dropped to the normal level approximately after 6 h, but the dropping did not happen in expression of c-Jun, it remained on the high level unweakened after repeated stimulation; SXP can remarkably down-regulate the proto-oncogene (c-Fos and c-Jun) expressions after psychological stress in mice.</p>
Subject(s)
Animals , Female , Male , Mice , Brain , Metabolism , Drugs, Chinese Herbal , Pharmacology , Hippocampus , Metabolism , Immunohistochemistry , Paraventricular Hypothalamic Nucleus , Metabolism , Proto-Oncogene Proteins c-fos , Proto-Oncogene Proteins c-jun , Stress, Psychological , Supraoptic Nucleus , MetabolismABSTRACT
Nitric oxide (NO), a free radical gas produced endogenously from the amino acid L-arginine by NO synthase (NOS), has important functions in modulating vasopressin and oxytocin secretion from the hypothalamo-neurohypophyseal system. NO production is stimulated during increased functional activity of magnocellular neurons, in parallel with plastic changes of the supraoptic nucleus (SON) and paraventricular nucleus. Electrophysiological data recorded from the SON of hypothalamic slices indicate that NO inhibits firing of phasic and non-phasic neurons, while L-NAME, an NOS inhibitor, increases their activity. Results from measurement of neurohypophyseal hormones are more variable. Overall, however, it appears that NO, tonically produced in the forebrain, inhibits vasopressin and oxytocin secretion during normovolemic, isosmotic conditions. During osmotic stimulation, dehydration, hypovolemia and hemorrhage, as well as high plasma levels of angiotensin II, NO inhibition of vasopressin neurons is removed, while that of oxytocin neurons is enhanced. This produces a preferential release of vasopressin over oxytocin important for correction of fluid imbalance. During late pregnancy and throughout lactation, fluid homeostasis is altered and expression of NOS in the SON is down- and up-regulated, respectively, in parallel with plastic changes of the magnocellular system. NO inhibition of magnocellular neurons involves GABA and prostaglandin synthesis and the signal-transduction mechanism is independent of the cGMP-pathway. Plasma hormone levels are unaffected by icv 1H-[1, 2, 4]oxadiazolo-[4,3-a]quinoxalin-1-one (a soluble guanylyl cyclase inhibitor) or 8-Br-cGMP administered to conscious rats. Moreover, cGMP does not increase in homogenates of the neural lobe and in microdialysates of the SON when NO synthesis is enhanced during osmotic stimulation. Among alternative signal-transduction pathways, nitrosylation of target proteins affecting activity of ion channels is considered.
Subject(s)
Animals , Rats , Hypothalamo-Hypophyseal System , Nitric Oxide , Nitric Oxide Synthase , Electrophysiology , Neurons , Signal Transduction , Supraoptic NucleusABSTRACT
Brain natriuretic peptide (BNP) is a neuropeptide, isolated from porcine brain that is homologous with atriopeptin. Magnocellular neurosecretory cells located in the paraventricular nucleus and supraoptic nucleus synthesize and secrete neurohormones. The purpose of this study was to investigate distribution of BNP immunoreactivity throughout the rat hypothalamus from the day of birth to 30 days and adult using immunoperoxidase and immunofluorescent staining. The first BNP immunoreactive neurons appeared in the paraventricular and supraoptic nucleus at P10. In adult, BNP immunoreactivity was widely distributed throughout regions of the hypothalamus including dorsomedial hypothalamic nucleus, ventromedial hypothalamic nucleus, arcuate nucleus and internal layer of median eminence. The intensity of BNP immunoreactivity was weak in almost all hypothalamic nuclei except the paraventricular and supraoptic nuclei. BNP immunoreactivity was first observed in the lateral hypothalamic area at P15. In retrochiasmatic supraoptic nucleus, BNP immunoreactivity was first observed at P20 and remarkably distributed in adult. In the present study, distinct localization of BNP immunoreactivity was in the hypothalamic cell bodies and fibers. Although the role of BNP in the brain is yet to be determined, these results indicate that BNP in the neurons of hypothalamus play important role in the regulation of a variety of neurosecretory functions as a neuromodulator during postnatal development of the hypothalamus.
Subject(s)
Adult , Animals , Humans , Rats , Arcuate Nucleus of Hypothalamus , Brain , Dorsomedial Hypothalamic Nucleus , Hypothalamic Area, Lateral , Hypothalamus , Immunohistochemistry , Median Eminence , Natriuretic Peptide, Brain , Neurons , Neuropeptides , Neurotransmitter Agents , Paraventricular Hypothalamic Nucleus , Parturition , Supraoptic Nucleus , Ventromedial Hypothalamic NucleusABSTRACT
Brain natriuretic peptide (BNP) is a neuropeptide, isolated from porcine brain that is homologous with atriopeptin. Magnocellular neurosecretory cells located in the paraventricular nucleus and supraoptic nucleus synthesize and secrete neurohormones. The purpose of this study was to investigate distribution of BNP immunoreactivity throughout the rat hypothalamus from the day of birth to 30 days and adult using immunoperoxidase and immunofluorescent staining. The first BNP immunoreactive neurons appeared in the paraventricular and supraoptic nucleus at P10. In adult, BNP immunoreactivity was widely distributed throughout regions of the hypothalamus including dorsomedial hypothalamic nucleus, ventromedial hypothalamic nucleus, arcuate nucleus and internal layer of median eminence. The intensity of BNP immunoreactivity was weak in almost all hypothalamic nuclei except the paraventricular and supraoptic nuclei. BNP immunoreactivity was first observed in the lateral hypothalamic area at P15. In retrochiasmatic supraoptic nucleus, BNP immunoreactivity was first observed at P20 and remarkably distributed in adult. In the present study, distinct localization of BNP immunoreactivity was in the hypothalamic cell bodies and fibers. Although the role of BNP in the brain is yet to be determined, these results indicate that BNP in the neurons of hypothalamus play important role in the regulation of a variety of neurosecretory functions as a neuromodulator during postnatal development of the hypothalamus.
Subject(s)
Adult , Animals , Humans , Rats , Arcuate Nucleus of Hypothalamus , Brain , Dorsomedial Hypothalamic Nucleus , Hypothalamic Area, Lateral , Hypothalamus , Immunohistochemistry , Median Eminence , Natriuretic Peptide, Brain , Neurons , Neuropeptides , Neurotransmitter Agents , Paraventricular Hypothalamic Nucleus , Parturition , Supraoptic Nucleus , Ventromedial Hypothalamic NucleusABSTRACT
Expression of c-Fos, an immediate early gene, has accepted to be a marker of functional activity in neurons. This study was aimed to investigate the dental pain pathway and the affection of dental pain on other brain regions such as the cardiovascular regulation center using c-Fos immunohistochemistry. Expression of c-Fos in Sprague Dawley rats weighting 300 ~350 gm was examined 1.5 hr after dental pain elicited by intrapulpal injecton of 2 M KCl into upper and lower incisor pulps exposed by bone cutter. c-Fos positive neurons were demonstrated in the trigeminal nucleus caudalis and the ventroposterior medial nucleus of thalamus known to be a sharp pathway. Dental pain enhanced mean arterial pressure and heart rate. In addition, c-Fos expression was induced in the rostral ventrolateral nucleus of medulla oblongata, nucleus tractus solitarius, paraventricular nucleus and supraoptic nucleus of hypothalamus, central presser areas of systemic blood pressure. These results suggest that trigeminal nucleus caudalis and ventroposterior medial nucleus of thalamus plays vital roles in the transmission of dental pain besides, dental pain affected the central cardiovescular regulation centers, resulting to the elevation of systemic blood pressure.
Subject(s)
Animals , Rats , Arterial Pressure , Blood Pressure , Brain , Heart Rate , Hypothalamus , Immunohistochemistry , Incisor , Medulla Oblongata , Neurons , Paraventricular Hypothalamic Nucleus , Rats, Sprague-Dawley , Reflex , Solitary Nucleus , Supraoptic Nucleus , Thalamus , Trigeminal NucleiABSTRACT
BACKGROUND AND OBJECTIVES: The vestibuloautonomic reflex controls respiration and blood pressure during locomotion. The purpose of this study was to investigate the role of the peripheral vestibular receptor in the control of blood pressure in sinoaortic denervated (SAD) rats. MATERIALS AND METHODS: The baroreceptor reflex was removed by SAD in labyrinthectomized rats. The expression of c-Fos protein in the vestibular nuclear complex, and other nuclei related to control of blood pressure, was measured following the induction of acute hypotension using sodium nitroprusside (SNP). RESULTS: The SNP induced acute hypotension, in intact labyrinthine rats, increased the expression of c-Fos protein in the supraoptic nucleus, paraventricular nucleus, rostral ventrolateral medulla, solitary nucleus, and vestibular nuclear complex. The expression of c-Fos protein, following the SNP induced acute hypotension in the SAD rats, increased the expression of c-Fos protein in the paraventricular nucleus, rostral ventrolateral medulla, and medial and inferior vestibular nuclei. The acute hypotension induced by SNP in a unilateral labyrinthectomy, with SAD, increased the expression of c-Fos protein in the contralesional vestibular nuclear complex, but decreased its expression in the ipsilesional vestibular nuclear complex. The acute hypotension induced by SNP in a bilateral labyrinthectomy, with SAD, showed only slight expression of c-Fos protein in the bilateral vestibular nuclear complex. CONCLUSION: These results suggest that the acute hypotension induced by SNP activates the vestibular nuclear neurons by decreasing the blood flow in the peripheral vestibular receptors, and that these in turn modulate blood pressure through activation of the catecholaminergic nervous system and neuroendocrine reflex.