Dorsal Medulla Research Articles

Hemangioblastoma quístico de la unión bulbomedular asociado a enfermedad de von Hippel-Lindau. Presentación de dos casos y revisión de la bibliografía

Hemangioblastomas are very highly vascularised benign tumours that can present either sporadically or in association with von Hippel-Lindau syndrome in 20% of cases. Only 5-20% of hemangioblastomas are located in the brainstem, and those that occur at the junction of the medulla and upper spinal cord are the ones that are less commonly diagnosed. Two young patients were diagnosed with von Hippel-Lindau disease after beginning with a cystic hemangioblastoma at the junction of the medulla and upper spinal cord as the first pathological manifestation. Both of them underwent a suboccipital craniotomy and the two lesions were completely removed without any kind of post-operative neurological deficits. One of the patients required a reintervention some years later due to a new recurrence of a symptomatic hemangioblastoma in the dorsal medulla. The genetic study conducted in both patients confirmed the presence of a mutation in the VHL gene, which is responsible for the syndrome they were suffering from. The presence of cystic hemangioblastomas of the junction of the medulla and upper spinal cord associated to von Hippel-Lindau disease is very rare. Despite the technical difficulties involved in removing them, the incorporation of the latest neuroimaging and microsurgery techniques has made it possible to significantly reduce the morbidity and mortality rate associated to the surgical treatment of such patients.

Expression patterns of the Egr1 and Egr3 genes during medaka embryonic development

Egr1 and Egr3 are zinc finger-type transcription factors and known as synaptic activity-inducible immediate-early genes. Egr1 also plays important roles in many aspects of vertebrate development. Egr3 is known as the gene that is related to biological rhythm and muscular development, but its behavior in the central nervous system during development is not clear. We cloned the cDNA of the egr1 and egr3 orthologs in medaka, and examined their expression patterns during embryonic development using whole-mount in situ hybridization. Medaka egr3 was the first cloned egr3 gene in fish. The expression of egr1 mRNA was first detected at 1 day post-fertilization (dpf). It was expressed in the whole embryonic body. At 3 dpf, the egr1 mRNA was strongly expressed in the telencephalon, diencephalon, hypothalamus, optic tectum, dorsal medulla oblongata, retina, heart, pharynx, and pectoral fin. The expression of egr3 mRNA was first detected at 3 dpf. It was expressed in the telencephalon, hypothalamus, optic tectum, and pharynx. By sectioning the whole-mount specimens, expression of both the egr1 and egr3 mRNAs were observed in the telencephalon, hypothalamus, and optic tectum. However, the positions at which the genes were expressed were different.

Are ATP and glutamate released from slowly adapting pulmonary stretch receptor afferents in the NTS?

Are ATP and glutamate released from slowly adapting pulmonary stretch receptor afferents in the NTS?

Determination of the human brainstem respiratory control network and its cortical connections in vivo using functional and structural imaging

This study combined functional and structural magnetic resonance imaging techniques, optimized for the human brainstem, to investigate activity in brainstem respiratory control centres in a group of 12 healthy human volunteers. We stimulated respiration with carbon dioxide (CO 2), and utilized novel methodology to separate its vascular from its neuronal effects upon the blood oxygen level dependent (BOLD) signal. In the brainstem we observed activity in the dorsal rostral pons (representing the Kölliker-Fuse/parabrachial (KF/PB) nuclei and locus coeruleus), the inferior ventral pons and the dorsal and lateral medulla. These areas of activation correspond to respiratory nuclei identified in recent rodent studies. Our results also reveal functional participation of the anteroventral (AV), ventral posterolateral (VPL) ventrolateral thalamic nuclei, and the posterior putamen in the response to CO 2 stimulation, suggesting that these centres may play a role in gating respiratory information to the cortex. As the functional imaging plane was limited to the brainstem and adjacent subcortical areas, we employed diffusion tractography to further investigate cortical connectivity of the thalamic activations. This revealed distinct connectivity profiles of these thalamic activations suggesting subdivision of the thalamus with regards to respiratory control. From these results we speculate that the thalamus plays an important role in integrating respiratory signals to and from the brainstem respiratory centres.

Sensory sciatic nerve afferent inputs to the dorsal lateral medulla in the rat

Investigations show the paratrigeminal nucleus (Pa5) as an input site for sensory information from the sciatic nerve field. Functional or physical disruption of the Pa5 alters behavioral and somatosensory responses to nociceptive hindpaw stimulation or sciatic nerve electrostimulation (SNS), both contralateral to the affected structure. The nucleus, an input site for cranial and spinal nerves, known for orofacial nociceptive sensory processing, has efferent connections to structures associated with nociception and cardiorespiratory functions. This study aimed at determining the afferent sciatic pathway to dorsal lateral medulla by means of a neuronal tract-tracer (biocytin) injected in the iliac segment of the sciatic nerve. Spinal cord samples revealed bilateral labeling in the gracile and pyramidal or cuneate tracts from survival day 2 (lumbar L1/L2) to day 8 (cervical C2/C3 segments) following biocytin application. From day 10 to day 20 medulla samples showed labeling of the contralateral Pa5 to the injection site. The ipsilateral paratrigeminal nucleus showed labeling on day 10 only. The lateral reticular nucleus (LRt) showed fluorescent labeled terminal fibers on day 12 and 14, after tracer injection to contralateral sciatic nerve. Neurotracer injection into the LRt of sciatic nerve-biocytin-treated rats produced retrograde labeled neurons soma in the Pa5 in the vicinity of biocytin labeled nerve terminals. Therefore, Pa5 may be considered one of the first sites in the brain for sensory/nociceptive inputs from the sciatic nerve. Also, the findings include Pa5 and LRt in the neural pathway of the somatosympathetic pressor response to SNS and nocifensive responses to hindpaw stimulation.

Expressions of phosphorylated cAMP response element‐binding protein and neuronal nitric oxide synthase in the dorsal medulla of Zucker Diabetic Fatty rats

The purpose of this study was to examine the expressions of phosphorylated cyclic‐AMP response element binding protein (pCREB) and neuronal NO synthase (nNOS) in the brainstem of Zucker Diabetic Fatty (ZDF) rats compared to age‐matched lean rats. Sections of rat medulla were examined by immunolabeling with a polyclonal antibody directed against nNOS and NADPH diaphorase histochemistry, a marker of nNOS activity. The brainstem nuclei were also visualized through double labeling the neurons by immunohistochemistry with anti‐pCREB antibody combined with NAPDH diaphorase reactivity. The number of nNOS immunostaining neurons and NAPDH diaphorase positive neurons were significantly decreased in the gracile nucleus and the medial nucleus tractus solitarius (mNTS), but not altered in other brainstem regions of ZDF rats compared to lean rats. pCREB positive cells containing NAPDH diaphorase reactivity were significantly decreased in the mNTS and gracile nucleus of ZDF rats compared to lean rats. The results show that pCREB neurons endowed with nNOS are decreased in the gracile nucleus and mNTS of ZDF rats. We conclude that reduced pCREB causes decreased nNOS‐NO level in the dorsal medulla, which modifies somatosensory functions in Type II diabetic rats. Supported by ADA 7–07–RA–100 and NIH RO1 AT 002478 to S. Ma.

Anatomy and function of group III metabotropic glutamate receptors in gastric vagal pathways

Metabotropic glutamate receptors (mGluR) are classified into groups I (excitatory), II and III (inhibitory) mGluR. Activation of peripheral group III mGluR (mGluR4, mGluR6, mGluR7, mGluR8), particularly mGluR8, inhibits vagal afferent mechanosensitivity in vitro which translates into reduced triggering of transient lower oesophageal sphincter relaxations and gastroesophageal reflux in vivo. However, the expression and function of group III mGluR in central gastrointestinal vagal reflex pathways is not known. Here we assessed the expression of group III mGluR in identified gastric vagal afferents in the nodose ganglion (NG) and in the dorsal medulla. We also determined the central action of the mGluR8a agonist S-3,4-DCPG (DCPG) on nucleus tractus solitarius (NTS) neurons with gastric mechanosensory input in vivo. Labelling for mGluR4 and mGluR8 was abundant in gastric vagal afferents in the NG, at their termination site in the NTS (subnucleus gelatinosus) and in gastric vagal motorneurons, while labelling for mGluR6 and mGluR7 was weaker in these regions. DCPG (0.1 nmol or 0.001–10 nmol i.c.v.) inhibited or markedly attenuated responses of 8/10 NTS neurons excited by isobaric gastric distension with no effect on blood pressure or respiration; 2 NTS neurons were unaffected. The effects of DCPG were significantly reversed by the group III mGluR antagonist MAP4 (10 nmol, i.c.v.). In contrast, 4/4 NTS neurons inhibited by gastric distension were unaffected by DCPG. We conclude that group III mGluR are expressed in peripheral and central vagal pathways, and that mGluR8 within the NTS selectively reduce excitatory transmission along gastric vagal pathways.

A Case of Multiple Sclerosis with Sick Sinus Syndrome and Postural Orthostatic Tachycardia Syndrome

A 19-year-old girl was admitted to our hospital with nausea, vomiting, hiccups, constipation and syncope. After hiccups or vomiting sinus arrest developed and lasted more than 5-8 seconds. She lost consciousness every one hour. Based on an electrocardiographic diagnosis of sick sinus syndrome (SSS), a temporary pacemaker was implanted. The next day, although her syncope and bradycardia disappeared, she had orthostatic tachycardia of over 120 beats/minute and swelling of the legs, which led to a diagnosis of postural orthostatic tachycardia syndrome (POTS). Neurologically, she showed the right-sided tongue deviation and parasympathetic system disorders revealed by coefficient of variation of R-R interval (CVR-R), the Achner eye-ball pressure test, the valsalva ratio, and the head-up-tilt test. Brain MRI disclosed a small hyperintense lesion on a T2-weighted image with gadolinium enhancement in the right dorsal medulla including the hypoglottis nucleus and the posterior nucleus of vagus. After steroid pulse therapy (methyl prednisolone 1 g/day×3 days, 5 times) was administered, this lesion became smaller and finally disappeared. Before the lesion disappeared, she was able to begin rehabilitation by wearing elastic stockings and treatment with midodrine hydrochloride. The following year, she developed other MRI-proven brain lesions, suggestive of demyelination. Such a spinal and temporal distribution of lesions led to a diagnosis of multiple sclerosis (MS). A case of POTS caused by MS has not been reported previously, however, MS often affects the medullary paraventricular regions associated with autonomic failures. Autonomic failures often prevent patients from experiencing early rehabilitations. We should promptly give symptomatic treatment against autonomic failures, which leads to good patient recovery not only in patient vitality but also functionality.

Neurochemical organization of the nucleus paramedianus dorsalis in the human

We have characterized the neurochemical organization of a small brainstem nucleus in the human brain, the nucleus paramedianus dorsalis (PMD). PMD is located adjacent and medial to the nucleus prepositus hypoglossi (PH) in the dorsal medulla and is distinguished by the pattern of immunoreactivity of cells and fibers to several markers including calcium-binding proteins, a synthetic enzyme for nitric oxide (neuronal nitric oxide synthase, nNOS) and a nonphosphorylated neurofilament protein (antibody SMI-32). In transverse sections, PMD is oval with its long axis aligned with the dorsal border of the brainstem. We identified PMD in eight human brainstems, but found some variability both in its cross-sectional area and in its A–P extent among cases. It includes calretinin immunoreactive large cells with oval or polygonal cell bodies. Cells in PMD are not immunoreactive for either calbindin or parvalbumin, but a few fibers immunoreactive to each protein are found within its central region. Cells in PMD are also immunoreactive to nNOS, and immunoreactivity to a neurofilament protein shows many labeled cells and fibers. No similar region is identified in atlases of the cat, mouse, rat or monkey brain, nor does immunoreactivity to any of the markers that delineate it in the human reveal a comparable region in those species. The territory that PMD occupies is included in PH in other species. Since anatomical and physiological data in animals suggest that PH may have multiple subregions, we suggest that the PMD in human may be a further differentiation of PH and may have functions related to the vestibular control of eye movements.

Wernicke Encephalopathy: MR Findings at Clinical Presentation in Twenty-Six Alcoholic and Nonalcoholic Patients

Wernicke encephalopathy is a severe neurologic disorder that results from a dietary vitamin B1 deficiency. It is characterized by changes in consciousness, ocular abnormalities, and ataxia. This study was undertaken to analyze and compare findings on MR imaging and neurologic symptoms at clinical presentations of patients with Wernicke encephalopathy with and without a history of alcohol abuse. A multicenter study group retrospectively reviewed MR brain imaging findings, clinical histories, and presentations of 26 patients (14 female, 12 male) diagnosed between 1999 and 2006 with Wernicke encephalopathy. The age range was 6-81 years (mean age, 46 .6+/-19 years). Fifty percent of the patients had a history of alcohol abuse, and 50% had no history of alcohol abuse. Eighty percent showed changes in consciousness, 77% had ocular symptoms, and 54% had ataxia. Only 38% of the patients showed the classic triad of the disease at clinical presentation. At MR examination, 85% of the patients showed symmetric lesions in the medial thalami and the periventricular region of the third ventricle, 65% in the periaqueductal area, 58% in the mamillary bodies, 38% in the tectal plate, and 8% in the dorsal medulla. Contrast enhancement of the mamillary bodies was statistically positively correlated with the alcohol abuse group. Our study confirms the usefulness of MR in reaching a prompt diagnosis of Wernicke encephalopathy to avoid irreversible damage to brain tissue. Contrast enhancement in the mamillary bodies is a typical finding of the disease in the alcoholic population.

Brain structural damage in Friedreich’s ataxia

Objective:Neuropathological descriptions of the brain in Friedreich’s ataxia (FRDA) were obtained before availability of the current molecular genetic tests for this disease. Voxel-based morphometry (VBM) enables an unbiased whole-brain quantitative...

Multiple Mechanosensory Modalities Influence Development of Auditory Function

Sensory development can be dependent on input from multiple modalities. During metamorphic development, ranid frogs exhibit rapid reorganization of pathways mediating auditory, vestibular, and lateral line modalities as the animal transforms from an aquatic to an amphibious form. Here we show that neural sensitivity to the underwater particle motion component of sound follows a different developmental trajectory than that of the pressure component. Throughout larval stages, cells in the medial vestibular nucleus show best frequencies to particle motion in the range from 15 to 65 Hz, with displacement thresholds of <10 mum. During metamorphic climax, best frequencies significantly increase, and sensitivity to lower-frequency (<25 Hz) stimuli tends to decline. These findings suggest that continued sensitivity to particle motion may compensate for the considerable loss of sensitivity to pressure waves observed during the developmental deaf period. Transport of a lipophilic dye from peripheral end organs to the dorsal medulla shows that fibers from the saccule in the inner ear and from the anterior lateral line both terminate in the medial vestibular nucleus. Saccular projections remain stable across larval development, whereas lateral line projections degenerate during metamorphic climax. Sensitivity to particle motion may be based on multimodal input early in development and on saccular input alone during the transition to amphibious life.

Neonatal-Onset Brainstem Reticular Reflex Myoclonus Following a Prenatal Brain Insult: Generalized Myoclonic Jerk and a Brainstem Lesion

Brainstem reticular reflex myoclonus (BRRM) is characterized by sudden, generalized, shock-like movements that can be elicited by sensory stimulation. We present a boy, born after 35 weeks gestation, who was diagnosed with neonatal-onset BRRM. Within 1 hr of birth, the patient showed spasticity and generalized clonic movements of all limbs elicited with tactile stimulation anywhere on the body. Surface electromyography showed co-contraction of agonistic and antagonistic muscles, revealing that his generalized clonic movements were tremulous myoclonus in nature. Brain magnetic resonance imaging (MRI) at 21 hrs after birth disclosed high-intensity lesions in the Rolandic area, thalamus, basal ganglia, and brainstem, including the dorsal pons and medulla, the center of BRRM, in T1-weighted images. Follow-up MRI at 1 month revealed dramatic improvement in the pontine lesion. The patient showed gradual remission of the characteristic movements, which disappeared at 1 year of age, but the patient died unexpectedly at 1 year and 3 months. In conclusion, neonatal BRRM arises as a result of severe brainstem injury, and the associated lesions may only be seen temporarily on MRI taken soon after birth.

Elevated mean diffusivity in widespread brain regions in congenital central hypoventilation syndrome

To investigate whether mean diffusivity (MD) values are altered in brain areas underlying cardiovascular and respiratory control in congenital central hypoventilation syndrome (CCHS). Conventional and diffusion tensor imaging were performed in 15 CCHS and 30 control subjects, using a 3.0-Tesla MRI unit. Mean diffusivity maps were calculated from diffusion-weighted images, spatially normalized, smoothed, and compared between groups using analysis of covariance at each voxel with age as covariate. Global mean MD values of gray and white matter were determined in individual subjects and compared between groups and with age. Increased MD values appeared in CCHS over control subjects within multiple areas influencing breathing and cardiovascular control, including the midbrain, pons, and dorsal and ventral medulla. Other altered sites included cerebellar cortex and deep nuclei, basal ganglia, basal forebrain, and temporal and frontal cortices. Global mean MD values for gray and white matter did not differ between groups; however, gray matter MD values significantly increased with age (P < 0.02) in CCHS patients only. Increased MD values suggest regional alterations or injury; affected areas include brainstem sites classically associated with autonomic and respiratory control. Other altered regions mediate additional physiological characteristics impaired in CCHS.

Leptin and thyrotropin-releasing hormone: Cooperative action in the hindbrain to activate brown adipose thermogenesis

Explanations of leptin induction of thermogenesis typically involve primary detection elements in the hypothalamus. In turn, these circuits control medullary raphe neurons that regulate spinal efferent sympathetic projections to heat-producing brown adipose tissue (BAT). The hindbrain may be capable of considerable thermoregulatory capacity independent of the hypothalamus, though little is known about the site(s), mechanism(s) of action, or the physiological consequences of leptin action in the hindbrain. Several reports describe the presence of leptin receptor in the solitary nucleus, and there is functional evidence that leptin can act in the dorsal medulla to suppress feeding. We examined the effects of leptin, applied to the dorsal medulla, on BAT thermogenesis. Leptin alone (≤ 25 μg) had no independent effect on BAT thermogenesis. We hypothesized that, while leptin may not be capable of activating thermocontrol mechanisms in the hindbrain directly, it may modulate the efficacy of other neural signals involved in the control of thermogenesis such as thyrotropin-releasing hormone (TRH). We tested the hypothesis that leptin and TRH, acting in the hindbrain, co-regulate thermogenesis. As expected, TRH (0.1 μg), alone, produces a small increase (+ 0.75 °C) in BAT temperature. Co-application of leptin (5 μg) and TRH (0.1 μg) to the dorsal medulla produces an increase in BAT and core temperature more than 300% greater than TRH alone (+ 3.5 °C). This effect is undiminished in the acute decerebrate rat, suggesting that the effect is mediated entirely by the hindbrain.

Repetitive acute shock following tracheal extubations after neurosurgery for a cerebellar tumor

) during the operation. The cerebellar tumor, adjacent to the dorsal pons and the rostral dorsal medulla, was resected. Spontaneous respiration resumed 20 min after the termination of the operation, when the oxygen saturation of the peripheral artery (SpO2 ) was 100% (when the fraction of inspiratory oxygen [FIO2 ] was 0.3) and the partial pressure of end-tidal carbon dioxide (PETCO2 ) was 40 mmHg. The patient spontaneously opened his eyes and gripped and opened his hand according to verbal command. Ulnar nerve stimulation on his hand showed a train-of-four ratio of 1.0. He coughed strongly when a suction catheter was inserted into the trachea. The tracheal tube was removed. After the extubation, his respiratory pattern showed tracheal tag. The SpO2 was above 98% during the first 3 min after the extubation, and decreased to 77% in the following 2 min. The systolic blood pressure rapidly dropped from 140 mmHg to 40 mmHg before the SpO2 decreased below 90%. His heart rate did not change significantly, until ephedrine was administered. There were no abnormalities in the monitored ECG. Tracheal intubation was performed 5 min after the extubation. The initial PETCO2 after the re-intubation was 60 mmHg. After positive pressure ventilation for 3 min, sufficient spontaneous respiration resumed,

Blood Oxygenation Level-Dependent Visualization of Synaptic Relay Stations of Sensory Pathways along the Neuroaxis in Response to Graded Sensory Stimulation of a Limb

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to test at which levels of the neuroaxis signals are elicited when different modalities of sensory information from the limbs ascend to cortex cerebri. We applied graded electric stimuli to the rat hindlimbs and used echo-planar imaging to monitor activity changes in the lumbar spinal cord and medulla oblongata, where primary afferents of painful and nonpainful sensation synapse, respectively. BOLD signals were detected in ipsilateral lumbar spinal cord gray matter using sufficiently strong stimuli. Using stimuli well below the threshold needed for signals to be elicited in the spinal cord, we found BOLD responses in dorsal medulla oblongata. The distribution of these signals is compatible with the neuroanatomy of the respective synaptic relay stations of the corresponding sensory pathways. Hence, the sensory pathways conducting painful and nonpainful information were successfully distinguished. The fMRI signals in the spinal cord were markedly decreased by morphine, and these effects were counteracted by naloxone. We conclude that fMRI can be used as a reliable and valid method to monitor neuronal activity in the rat spinal cord and medulla oblongata in response to sensory stimuli. Previously, we also documented BOLD signals from thalamus and cortex. Thus, BOLD responses can be elicited at all principal synaptic relay stations along the neuroaxis from lumbar spinal cord to sensory cortex. Rat spinal cord fMRI should become a useful tool in experimental spinal cord injury and pain research.

Serotonin-3 receptors in gastric mechanisms of cholecystokinin-induced satiety

our understanding of the controls of food intake has increased substantially during the last 30 years. Important in this has been the recognition of the meal as a controlled, physiologically relevant unit of energy intake. During a meal, ingested nutrients accumulate in the stomach and gradually

Reduced Formation of Ang‐(1–7) by ACE2 in Dorsal Medulla Oblongata of Sprague‐Dawley (SD) and ASrAogen Rats During Aging

Angiotensin (Ang) II and Ang-(1–7) have opposing effects on the baroreceptor reflex; loss of Ang-(1–7) with effects of Ang II unopposed may account for decreased baroreceptor function during aging. In medulla oblongata, we identified the enzymes present and activities forming Ang-(1–7) from 125I-Ang I or 125I-Ang II, how activity changes with aging and how it differs in transgenic rats (ASrAogen) with reduced glial angiotensinogen. Both angiotensin converting enzyme (ACE) 2 and neprilysin (NEP) mRNA as determined using RT-PCR tended to decrease ~15–20 % during aging (15 wks vs 70 wks of age), with significant reductions for NEP mRNA in older SD rats (p<0.05) and ACE2 mRNA in older ASrAogen rats (p<0.05). ACE mRNA was not different between older and younger animals of either strain and no significant differences in mRNA for the three enzymes were detected between strains. ACE, ACE2 and NEP activities detected in solubilized membranes obtained from dorsal medulla at either age were not different between SD and ASrAogen rats. NEP activity tended to decline during aging in ASrAogen (63%) and SD (40%) animals with ~36% lower ACE2 activity in older rats of both strains. ACE activity did not change with age. The reductions in activity of NEP and ACE2 account for ~40% less overall Ang (1–7) formation in older animals. Thus, NEP and ACE2 are present and active in processing of Ang peptides in rat dorsal medulla. ACE2 appears to be predominant in formation of Ang-(1–7) and loss of Ang-(1–7) formation rather than an increase in Ang II may contribute to impaired baroreceptor reflexes in older individuals (Support: HL-51952; HL-56973).

Differential mRNA expression of cyclic‐AMP response element binding protein and neuronal nitric oxide synthase in the dorsal medulla of salt‐sensitive and salt resistant Dahl rats

The purpose of this study was to examine the mRNA levels of cyclic-AMP response element binding protein (CREB) and neuronal nitric oxide synthase (nNOS) in the dorsal medulla of Dahl salt sensitive (DS) and salt resistant (DR) rats. The rats were fed either a regular salt (0.2% NaCl) or a high salt (8% NaCl) diet for three weeks (n= 5 /group). Mean arterial pressure was increased in DS rats (174±10 [mean±SE]) compared to DR rats on high salt (105±4). The animals were sacrificed by decapitation; brain was immediately removed and kept in RNA Later. Gracile nucleus (GR) and nucleus of tractus solitarius (NTS) regions were isolated by micropunch technique from brain sections. Total RNA was isolated and quantitative real time PCR was carried out. mRNA levels of CREB in the NTS region were increased 1.67-fold in DS rats and 1.6-fold in DR rats with high salt compared with the regular salt (p<0.05). nNOS mRNA increased 2.7-fold in both high salt DS and DR rats compared to the normal salt rats (p=0.09). In the GR regions, high salt tended to increase mRNA levels of CREB and nNOS in both DS and DR rats. The results show that high salt diet increases mRNA levels of CREB and nNOS in the NTS region, possibly in the GR region, of DR and DS rats. We conclude that salt loading induces up- regulation of CREB and nNOS mRNA in the dorsal medulla which may contribute to central regulation of the circulation during salt metabolism. Supported by NIH (AT002478, HL04447, and AT00450) to S. Ma.