Rat Brainstem Nuclei Research Articles

The role of Sirt3‐AMPK in mediating oxidative stress‐induced hypertension in the brain stem nuclei of rats

Essential hypertension is the most common cardiovascular disease and is a major risk factor for stroke and heart disease. It is known the nucleus tractus solitarii (NTS) located on the dorsal medulla play an important role in regulating cardiovascular responses. More recently, metabolic syndrome‐induced phosphorylated AMPK defect has been demonstrated to underline the initiation of superoxide elevation. In recent years, fructose induces a decrease in SOD2 activity, which leads to a large increase in superoxide and a decrease in the pathway of Akt‐nNOS. Studies have found that stimulation with abnormal diet factor can promote the reduction of Sirt3 and increase the content of superoxide. Therefore, we hypothesize that the SOD2 activity in the NTS was inhibited via Sirt3‐AMPK dysfunction induced superoxide expression and hypertension. During this study, the rats were fed 10% fructose with or without natural compound 3H‐1,2‐Dithiole‐3‐thione (D3T) for 4 weeks with the D3T treatment beginning at week 2. The systolic blood pressure and serum fasting high‐density lipoprotein decreased significantly in the D3T‐treated group compared fructose‐fed group after feeding D3T for 2 weeks. The protein levels of Sirt3, and AMPKT172 showed a significant increase in the D3T‐treated group compared fructose group after feeding D3T for 2 weeks by immunoblotting analyses. However, the acetylation of SOD2 were significantly decreased in the D3T‐fed group compared the fructose‐fed groups. Superoxide anion expression levels in the NTS were clearly eliminated in the D3T‐fed group compared the fructose‐fed groups. Collectively, fructose induced Sirt3 and AMPK defect and acetylation of SOD2 in the NTS of fructose‐fed rats, while treatment of D3T in the fructose‐fed rat reversed the effect. This study suggest that fructose‐induced hypertension may through Sirt3‐AMPK to mediate the acetylation of SOD2 and causes superoxide generation in the central nervous system. Our findings suggested a better understanding of complex cardiovascular neural pathways and may provide a new link between hypertension and neuronal superoxide that could be targeted for the treatment of cardiometabolic diseases.Support or Funding InformationThis work was supported by funding from the Ministry of Science and Technology (MOST‐107‐2320‐B‐075B‐002).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Comparisons of Neuronal and Excitatory Network Properties between the Rat Brainstem Nuclei that Participate in Vertical and Horizontal Gaze Holding.

Gaze holding is primarily controlled by neural structures including the prepositus hypoglossi nucleus (PHN) for horizontal gaze and the interstitial nucleus of Cajal (INC) for vertical and torsional gaze. In contrast to the accumulating findings of the PHN, there is no report regarding the membrane properties of INC neurons or the local networks in the INC. In this study, to verify whether the neural structure of the INC is similar to that of the PHN, we investigated the neuronal and network properties of the INC using whole-cell recordings in rat brainstem slices. Three types of afterhyperpolarization (AHP) profiles and five firing patterns observed in PHN neurons were also observed in INC neurons. However, the overall distributions based on the AHP profile and the firing patterns of INC neurons were different from those of PHN neurons. The application of burst stimulation to a nearby site of a recorded INC neuron induced an increase in the frequency of spontaneous EPSCs. The duration of the increased EPSC frequency of INC neurons was not significantly different from that of PHN neurons. The percent of duration reduction induced by a Ca2+-permeable AMPA (CP-AMPA) receptor antagonist was significantly smaller in the INC than in the PHN. These findings suggest that local excitatory networks that activate sustained EPSC responses also exist in the INC, but their activation mechanisms including the contribution of CP-AMPA receptors differ between the INC and the PHN.

Distribution of Heme Oxygenase-2 in the Brainstem Nuclei of Rats

Immunocytochemical method was used to determine the distribution of neurons expressing heme oxygenase-2 (HO-2-positive neurons) in the nuclei of various parts of the brainstem of 16 male Wistar rats. The sizes of neurons and the optical density of the product of histochemical reaction in their cytoplasm were determined in the nuclei studied. HO-2-positive neurons, differing in shape, size and numbers, were identified in the nuclei of the medulla oblongata, pons and midbrain. HO-2-positive cells were found 3-5 times more frequently in the sensory nuclei as compared to the motor ones. At the same time, relatively large number of nuclei was detected, which contained either no or a few HO-2-positive neurons.

Evaluation of c-Fos immunoreactivity in the rat brainstem nuclei relevant in migraine pathogenesis after electrical stimulation of the trigeminal ganglion

Migraine is a common neurological condition, causing high disability, but the pathomechanism of the disease is not yet fully understood. Activation of the trigeminovascular system could play a crucial role in the manifestation of the symptoms, but initial step of this activation remains unknown. Functional imaging studies have revealed that certain brainstem areas, referred to as migraine generators, are activated during a migraine attack, including the dorsal raphe, the periaqueductal gray, the locus coeruleus, and the nucleus raphe magnus. However, the studies performed to date have not demonstrated whether this activation is a trigger or a consequence of the migraine attack. With the aim of evaluating the functional relationship between activation of the trigeminal system and migraine generators, we examined the changes in c-Fos immunoreactivity in the above-mentioned nuclei after stimulation of the trigeminal ganglion, an animal model for trigeminovascular activation. The stimulation led to significant increases in the number of c-Fos immunoreactive cells in the nucleus raphe magnus and in the caudal part of the spinal trigeminal nucleus, 2 and 4 h after the stimulation. Activation of the trigeminal system failed to exhibit uniform activation of the brain stem nuclei related to migraine. Our results suggest that the activation of the trigeminal system in the rat by electrical stimulation of the trigeminal ganglion leads to the activation of the descending pain modulatory system, but not to the activation of "migraine generator" nuclei. Therefore, the activity pattern seen in functional studies may reflect a unique feature, exclusively present in migraine.

Persistent effects of early augmented acoustic environment on the auditory brainstem

Acoustic experiences significantly shape the functional organization of the auditory cortex during postnatal "critical periods." Here, we investigate the effects of a non-traumatic augmented acoustic environment (AAE) on the central nucleus of the inferior colliculus (ICC) and lower brainstem nuclei in rat during the critical period. Our results show that an AAE during P9-P28 had a persistent effect on the evoked auditory brainstem responses leading to a decreased latency and an increased amplitude of the response at and above the frequency of the stimulus used for the AAE. These findings are correlated with increased numbers of sites in the ICC that responded to the AAE frequency and show higher thresholds. There also were persistent effects in neurons with a best frequency higher than the AAE stimulus. These neurons showed decreased activity at low sound levels in the low frequency tail of the frequency response area. This was at, below and above the AAE stimulus frequency. Less often, increased activity at higher sound levels also was seen. Together, these findings suggest multifaceted interactions between activity-dependent plasticity, homeostasis, and development in the brainstem during the initial stages of hearing. A neonate exposed to an altered auditory environment may experience long-lasting change over the entire network of the auditory system.

Serotonin and tryptophan hydroxylase in isolated hypothalamic and brain stem nuclei of rats exposed to acute and repeated immobilization stress.

The effect of acute and repeated immobilization stress on serotonin concentration and tryptophan hydroxylase activity in some isolated hypothalamic and brain stem nuclei was measured using a special microdissection technique and sensitive isotopic-enzymatic microassays. In acutely immobilized rats serotonin concentration was increased in the median eminence, ventromedial and dorsomedial nuclei. In repeatedly immobilized rats increased serotonin concentration was recorded in the dorsomedial nucleus immediately after seven, and in the median eminence after forty consecutive daily exposures to immobilization. Decreased tryptophan hydroxylase activity was found in the suprachiasmatic nucleus after seven exposures to immobilization stress. Acute and repeated immobilization stress failed to produce any changes of serotonin concentration in the isolated brain stem nuclei studied, and of tryptophan hydroxylase activity in the dorsal raphe nucleus and n. centralis superior. The increased tryptophan hydroxylase activity observed without any changes in serotonin concentration in the locus coeruleus after the 7th immobilization may suggest an increased synthesis and release rate of serotonin in serotonergic nerve terminals in this area. The changes of serotonin concentration in some hypothalamic nuclei under the first exposure of rats to stress indicate the involvement of serotonin in the activation of the pituitary-adrenocortical system as well as in other neuroendocrine reactions initiated in the hypothalamus during acute stress. On the basis of the results presented, the presumed role of the serotonergic system in the regulation of pituitary-adrenocortical stress response in repeatedly stressed rats has not been established. The reported response of brain tryptophan hydroxylase to the release of endogenous corticosterone could not be confirmed in our experiments.

Hyperbaric oxygenation reduces overexpression of c-Fos and oxidative stress in the brain stem of experimental endotoxemic rats

Septic encephalopathy is associated with an increased mortality rate in septic patients. We have previously shown that a peripheral lipopolysaccharide (LPS) injection induces neuronal activation in the brain-stem nuclei of rats. Nitric oxide (NO) and superoxide are involved in LPS-induced brain damage. Hyperbaric oxygenation (HBO) provides protective effects against systemic oxidative stress and mortality in animals with septic shock. We examined the effects of HBO on neuronal activation and oxidative stress in the brain-stem nuclei of LPS-treated rats. Wistar rats were randomly distributed into six groups for the following treatments:(a) normal saline injection (NS); (b) HBO; (c) LPS; (d) LPS-HBO; (e) LPS-aminoguanidine (AG, an inhibitor of inducible nitric oxide synthase); or (f) hydralazine (HYD, a direct vasodilator). The HYD induces prolonged hypotension and was used as a comparison for LPS stimulation. The AG was used as a comparison for HBO treatment. Two HBO sessions were administered, 1 and 4[Symbol: see text]h after LPS. HBO and AG significantly reversed the overproduction of c-Fos induced by LPS in the brain stems of rats, with greater reversal in the nucleus tractus solitarii (NTS) by HBO. Although AG did not reduce the superoxide level, HBO significantly abolished superoxide production and NADPH diaphorase expression in the brain stems of LPS-treated rats. The HYD induced much lower c-Fos expression in the brain-stem nuclei than that in LPS-treated animals and caused no significant increase in NADPH diaphorase expression or superoxide formation. HBO protects against endotoxin-related neuronal activation and oxidative stress in the brain-stem nuclei of rats.

Developmental changes in the expression of GABA A receptor subunits α1, α2, and α3 in brain stem nuclei of rats

Gamma-aminobutyric acid (GABA) A receptor subunit switching is a suggested postnatal mechanism for changes in GABA transmission from depolarization to hyperpolarization. Previously, we found an apparent switch between GABA A α3 and α1 subunit expression in the rat pre-Bötzinger complex (PBC) on postnatal day (P) 12, a presumed peak critical period of respiratory nuclei development. The present study aimed at determining if GABA A subunit switching occurred in another respiratory nucleus, the ventrolateral subnucleus of the solitary tract nucleus (NTS VL), and in a non-respiratory cuneate nucleus (CN) of P0 to P21 rats. In both nuclei: (1) the expression of GABA A α1 subunit was relatively low at birth but increased with development; (2) that of GABA A α3 was relatively high at birth but declined with age; and (3) GABA A α2 remained relatively low and constant throughout development. However, the specific patterns differed between the two nuclei, but were similar between the NTS VL and the PBC. In the NTS VL, GABA A α1 expression gradually increased from birth and peaked at P12, whereas that in the CN sharply rose from P7 and peaked at P10. GABA A α3 expression had a prominent decrease from P11 to P12 in the NTS VL, whereas that in the CN only gradually declined from P10 to P12. The developmental trends of α1 and α3 in the NTS VL intersected close to P12, whereas those in the CN intersected at P10. Despite differences in timing, GABA A α subunit switching may be a common theme in the brain stem that may mediate different functional properties of GABA transmission.

Postnatal developmental expressions of neurotransmitters and receptors in various brain stem nuclei of rats

Previously, we reported that the expression of cytochrome oxidase in a number of brain stem nuclei exhibited a plateau or reduction at postnatal day (P) 3-4 and a dramatic decrease at P12, against a general increase with age. The present study examined the expression of glutamate, N-methyl-D-aspartate receptor subunit 1 (NMDAR1), GABA, GABAB receptors, glycine receptors, and glutamate receptor subunit 2 (GluR2) in the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, medial accessory olivary nucleus, dorsal motor nucleus of the vagus, and cuneate nucleus, from P2 to P21 in rats. Results showed that 1) the expression of glutamate increased with age in a majority of the nuclei, whereas that of NMDAR1 showed heterogeneity among the nuclei; 2) GABA and GABAB expressions decreased with age, whereas that of glycine receptors increased with age; 3) GluR2 showed two peaks, at P3-4 and P12; and 4) glutamate and NMDAR1 showed a significant reduction, whereas GABA, GABAB receptors, glycine receptors, and GluR2 exhibited a concomitant increase at P12. These features were present but less pronounced in hypoglossal nucleus and dorsal motor nucleus of the vagus and were absent in the cuneate nucleus. These data suggest that brain stem nuclei, directly or indirectly related to respiratory control, share a common developmental trend with the pre-Botzinger complex in having a transient period of imbalance between inhibitory and excitatory drives at P12. During this critical period, the respiratory system may be more vulnerable to excessive exogenous stressors.

Non-angiotensin II [ 125I] CGP42112 binding is a sensitive marker of neuronal injury in brainstem following unilateral nodose ganglionectomy: Comparison with markers for activated microglia

Previously we reported that a non-angiotensin II [ 125I] CGP42112 binding site is up-regulated in rat brainstem nuclei as a result of unilateral nodose ganglionectomy. In the present study, we compared non-angiotensin II [ 125I] CGP42112 binding with microglia/macrophage activation following nodose ganglionectomy, using both in vitro autoradiography and immunohistochemistry. Specific [ 125I] CGP42112 binding was observed in the nucleus of the solitary tract (NTS) and revealed an AT 2 receptor component as well as a non-angiotensin II receptor component. Subsequent to unilateral nodose ganglionectomy, [ 125I] CGP42112 binding in the ipsilateral NTS was increased approximately two-fold and was also induced in the ipsilateral dorsal motor nucleus (DMX) and the nucleus ambiguus (n.amb). This non-angiotensin II [ 125I] CGP42112 binding site was displaced by CGP42112 but not other ligands. Increased [ 3H] PK11195 binding (a known marker of reactive gliosis) was also observed in the same brainstem nuclei as non-angiotensin II [ 125I] CGP42112 binding after nodose ganglionectomy. The similarity in binding patterns between [ 125I] CGP42112 and [ 3H] PK11195 was shown to be primarily due to retrograde degeneration in the ipsilateral NTS, DMX and n.amb, as both radioligands were localized to similar cellular targets within the interstial space and over cellular debris. Immunohistochemical data confirmed reactive gliosis within the ipsilateral NTS, DMX and n.amb, following nodose ganglionectomy, which was predominantly characterized by an increase in OX-42 immunoreactivity (a marker for activated microglia/macrophages), with only a small increase in glial fibrillary acidic protein immunoreactivity (a marker of astrogliosis) detected. These data demonstrate for the first time that non-angiotensin II [ 125I] CGP42112 binding is associated with activated microglia, as well as macrophages, following unilateral nodose ganglionectomy. Furthermore, these studies also demonstrate the potential use of non-angiotensin II [ 125I] CGP42112 binding as a marker for quantitating inflammatory events which occur as a result of damage to the CNS.

Postnatal changes in cytochrome oxidase expressions in brain stem nuclei of rats: implications for sensitive periods.

Previously, we reported that cytochrome oxidase (CO) activity in the rat pre-Bötzinger complex (PBC) exhibited a plateau on postnatal days (P) 3-4 and a prominent decrease on P12 (Liu and Wong-Riley, J Appl Physiol 92: 923-934, 2002). These changes were correlated with a concomitant reduction in the expression of glutamate and N-methyl-d-aspartate receptor subunit 1 and an increase in GABA, GABAB, glycine receptor, and glutamate receptor 2. To determine whether changes were limited to the PBC, the present study aimed at examining the expression of CO in a number of brain stem nuclei, with or without known respiratory functions from P0 to P21 in rats: the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, nucleus raphe obscurus, dorsal motor nucleus of the vagus nerve, medial accessory olivary nucleus, spinal nucleus of the trigeminal nerve, and medial vestibular nucleus (MVe). Results indicated that, in all of the brain stem nuclei examined, CO activity exhibited a general increase with age from P0 to P21, with MVe having the slowest rise. Notably, in all of the nuclei examined except for MVe, there was a plateau or decrease at P3-P4 and a prominent rise-fall-rise pattern at P11-P13, similar to that observed in the PBC. In addition, there was a fall-rise-fall pattern at P15-P17 in these nuclei, instead of a plateau pattern in the PBC. Our data suggest that the two postnatal periods with reduced CO activity, P3-P4 and especially P12, may represent common sensitive periods for most of the brain stem nuclei with known or suspected respiratory control functions.

Neuronal nitric oxide synthase (bNOS) messenger RNA and protein expression in developing rat brainstem nuclei

Neuronal nitric oxide synthase (bNOS) messenger RNA expression and immunoreactivity were mapped in series of cryosections through the developing rat brainstem nuclei. Between embryonic day E16 and postnatal day P16, brainstem nuclei expressed both bNOS messenger RNA (mRNA) in situ hybridization signals and protein immunoreactivity. However, NOS mRNA signals were absent from the Edinger Westphal, facial or motory trigeminal nucleus. Strong patterns of mRNA signals and immunoreactivity occurred in neurons located in the substantia nigra pars compacta and the laterodorsal tegmental nuclei. Between E24 and P16, altered patterns of bNOS mRNA positive and immunoreactive neurons, e.g. superior and inferior colliculi, raphe nuclei, solitary tract or pontine nucleus were documented. Altered NOS expression patterns thus may reflect developmental processes within distinct neuronal populations such as cell phenotype discrimination or synaptogenesis within efferent or afferent brainstem pathways. The NOS/NO system therefore appears to be a modulator for intra-/intercellular adjustment processes in normal development.

Hypocretin-1 activates G proteins in arousal-related brainstem nuclei of rat.

The hypocretin (hcrt) ligand-receptor system contributes to the maintenance of wakefulness. Hypocretin receptors are coupled to guanine nucleotide binding (G) proteins and the present study tested the hypothesis that hcrt-1 would activate G proteins in rat brainstem nuclei known to regulate arousal states. In vitro [35S]GTPgammaS autoradiography was performed using coronal brain stem sections from six rats. Hcrt-1 (200 nM) significantly increased [35S]GTPgammaS binding over basal levels in locus coeruleus (24%), dorsal raphe nucleus (12%), pontine reticular nucleus, oral part (28%), and pontine reticular nucleus, caudal part (40%). This is the first study to quantify and localize hcrt-1-induced G protein activation in specific brain stem nuclei. The finding that hcrt-1 stimulated [35S]GTPgammaS binding suggests that some hcrt receptors in pontine brain stem couple to inhibitory G proteins.

Three-dimensional computerised atlas of the rat brain stem precerebellar system: approaches for mapping, visualization, and comparison of spatial distribution data.

Comparisons of microscopical neuroanatomic data from different experiments and investigators are typically hampered by the use of different section planes and dissimilar techniques for data documentation. We have developed a framework for visualization and comparison of section-based, spatial distribution data, in brain stem nuclei. This framework provides opportunities for harmonized data presentation in neuroinformatics databases. Three-dimensional computerized reconstructions of the rat brain stem and precerebellar nuclei served as a basis for establishing internal coordinate systems for the pontine nuclei and the precerebellar divisions of the sensory trigeminal nuclei. Coordinate based diagrams were used for presentation of experimental data (spatial distribution of labelled neurons and axonal plexuses) from standard angles of view. Each nuclear coordinate system was based on a cuboid bounding box with a defined orientation. The bounding box was size-adjusted to touch cyto- and myeloarchitectonically defined boundaries of the individual nuclei, or easily identifiable nearby landmarks. We exemplify the use of these internal coordinate systems with dual retrograde neural tracing data from pontocerebellar and trigeminocerebellar systems. The new experimental data were combined, in the same coordinate based diagrams, with previously published data made available via a neuroinformatics data repository (www.nesys.uio.no/Database, see also www.cerebellum.org). Three-dimensional atlasing, internal nuclear coordinate systems, and consistent formats for presentation of neuroanatomic data in web-based data repositories, offer new opportunities for efficient analysis and re-analysis of neuroanatomic data.

Expression of metabotropic glutamate receptors mRNA in the thalamus and brainstem of monoarthritic rats

Evidence for the involvement of metabotropic glutamate receptors (mGluR) in sensory processing has been emerging. Additionally, the differential distribution of distinct mGluR subtypes mRNA in particular thalamic nuclei of normal rats suggests that they could be involved in the processing of somatosensory information. In the present study, mGluR1, 3, 4 and 7 mRNAs expression was investigated by in situ hybridisation in selected brainstem and thalamic nuclei of adult monoarthritic rats at different time points of the disease (2, 4 and 14 days). Monoarthritic rats displayed behavioural and physical signs of painful arthritis at all time points. At 2 days of monoarthritis the mGluR1 mRNA expression was decreased mainly in the ventrobasal complex (VB) and in the posterior thalamic nuclei (Po) contralateral to the inflamed joint. The mGluR4 mRNA expression was also reduced, but minimum values were found at 4 days of monoarthritis, when no changes could be found in mGluR1 mRNA expression. At 14 days, mGluR4 mRNA expression was similar to controls, while mGluR1 mRNA was again reduced. Similar decreases of mGluR7 mRNA expression in the VB and Po were found at all time points, while mGluR3 mRNA expression was bilaterally increased in the reticular thalamic nucleus (Rt). In the brainstem no changes could be found in the expression of any mGluR subtype mRNA. The reduced expression of mGluR1, 4 and 7 transcripts in VB and Po, and the increases of mGluR3 mRNA in the Rt may contribute to counteract the increased noxious input arising from the periphery.

Fos expression in brain stem nuclei of pregnant rats after hydralazine-induced hypotension.

Fos and dopamine beta-hydroxylase immunoreactivity were evaluated in the brain stems of 21-day pregnant and virgin female rats injected with either hydralazine (HDZ; 10 mg/kg iv) or vehicle. HDZ produced significant hypotension in both groups, although baseline blood pressure was lower in pregnant rats (96 +/- 2.5 mmHg) than in virgin female rats (121 +/- 2.8 mmHg). There were no differences in Fos immunoreactivity in the brain stems of pregnant and virgin female rats after vehicle treatment. HDZ-induced hypotension significantly increased Fos expression in both groups; however, the magnitude of the increases differed in the caudal ventrolateral medulla (CVL), the area postrema (AP), and the rostral ventrolateral medulla (RVL). Fos expression after HDZ in pregnant rats was augmented in noncatecholaminergic neurons of the CVL but was attenuated in the AP and in noncatecholaminergic neurons in the RVL. These results are consistent with differences in the sympathetic response to hypotension between pregnant and virgin female rats and indicate that the central response to hypotension may be different in pregnant rats.

Opioids activate G proteins in REM sleep-related brain stem nuclei of rat.

Mu opioid receptors within the pontine reticular formation contribute to opioid-induced rapid eye movement (REM) sleep inhibition. Mu receptors are coupled to guanine nucleotide binding (G) proteins and this study tested the hypothesis that the micro opioid agonist [D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO) would activate G proteins in rat brain stem nuclei known to regulate REM sleep. In vitro autoradiography of DAMGO-stimulated [35S]GTPgammaS binding showed that, compared with basal [35S]GTPgammaS binding, DAMGO significantly increased G protein activation in the nucleus pontis oralis (56.2%), nucleus pontis caudalis (57.3%), laterodorsal tegmental nucleus (75.8%), pedunculopontine tegmental nucleus (72.4%), nucleus locus coeruleus (77.2%) and dorsal raphe nucleus (73.4%). DAMGO stimulation of [35S]GTPgammaS binding in nuclei regulating REM sleep suggests that opioid-induced REM sleep inhibition involves activation of G proteins.

Effect of Hemilabyrinthectomy on Monoamine Metabolism in the Medial Vestibular Nucleus, Locus Coeruleus, and Other Brainstem Nuclei of Albino and Pigmented Rats

We compared in albino and pigmented rats the early effect of unilateral labyrinthectomy (UL) on the concentrations of monoamines (norepinephrine, dopamine, serotonin) and their respective metabolites--3-methoxy,4-hydroxyphenylglycol (MHPG), 3,4-dihydroxy-phenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5HIAA)--in medial vestibular nuclei (MVN), locus coeruleus, raphe dorsalis, and cochlear nuclei. The study was conducted 6 hours after UL in both strains, differing by the functional optokinetic responses of their central vestibular neurons and the time-course of their vestibular compensation. The results show that the monoaminergic changes are different in the two rat strains. In the MVN of albino rats, there was a bilateral increase of MHPG and an ipsilateral increase of dopamine suggesting activation of norepinephrine synthesis and metabolism, whereas no such changes were observed in the MVN of pigmented rats. On the other hand, the simultaneous increase of norepinephrine and DOPAC observed in the contralateral locus coeruleus of albino rats suggested enhanced norepinephrine synthesis, whereas in pigmented rats the decreased norepinephrine content found in the ipsilateral locus coeruleus might reflect an earlier strong stimulation of NE release. These biochemical results confirm the relevant role of locus coeruleus noradrenergic innervation in vestibular compensation and also point out the involvement of norepinephrine of the MVN in the early stages of this process. The different strain-related noradrenergic responses observed on the 6th hour suggest that the involvement of central norepinephrine, particularly from locus coeruleus innervation, may be more crucial and more sustained in the albino than in pigmented rats. No serotonin and 5HIAA changes were found in either brainstem nuclei of albino rats. In contrast, the increase of the ratio 5HIAA/5HT observed in raphe dorsalis, in ipsilateral locus coeruleus, and in both sides of MVN of pigmented rats suggested that UL induced an extended and enhanced utilization of 5HT in this strain.

Cardiovascular Effects of Nitric Oxide in the Brain Stem Nuclei of Rats

Nitric oxide, synthesized from the semiessential amino acid L-arginine by nitric oxide synthase, is a remarkable regulatory molecule and plays an important role in physiological functions. However, the physiological role of nitric oxide in cardiovascular regulation by the central nervous system is not well understood. In this study we investigated the cardiovascular effects of nitric oxide in the lateral ventricle, nucleus tractus solitarii, area postrema, and rostral ventrolateral medulla in urethane-anesthetized male Sprague-Dawley rats. Microinjection of NG-monomethyl-L-arginine, a nitric oxide synthase inhibitor, into the cerebral ventricle of rats elicited a dose-dependent increase in blood pressure and heart rate. This suggests that nitric oxide may be involved in central cardiovascular regulation. Unilateral microinjection (60 nL) of L-arginine (1 to 100 nmol) into the nucleus tractus solitarii and rostral ventrolateral medulla produced prominent dose-related depressor and bradycardic effects and reduced renal sympathetic nerve activity. However, L-arginine had no significant cardiovascular effects in the area postrema. In addition, 4 to 6 hours after intravenous injection of bacterial endotoxin-lipopolysaccharide (10 mg/kg), there was a time-related potentiation of the L-arginine-induced depressor and bradycardic effects in the nucleus tractus solitarii. These results indicate that nitric oxide is involved in central cardiovascular regulation. The depressor effect of nitric oxide in the nucleus tractus solitarii and rostral ventrolateral medulla may be through inhibition of renal sympathetic nerve activity.

Cysteamine impairs the development of the acoustic startle response in rats: possible role of somatostatin

Somatostatin is transiently expressed in many regions of the developing brain, among others in auditory brainstem nuclei of neonatal rats. To explore the functional significance of somatostatin during the ontogeny of acoustically elicited behavior, the acoustic startle response (ASR) was measured in developing rats after chronic application of cysteamine, which, when applied in low doses, most selectively depletes somatostatin. Cysteamine treatment drastically reduced somatostatin immunoreactivity in the cochlear nuclear complex and the caudal pontine reticular nucleus, i.e. in structures mediating the ASR. It did not affect the ASR amplitude of postnatal day (P) 13 animals, yet it resulted in a significant reduction of the ASR amplitude at P18. Our results therefore suggest that somatostatin can influence the maturation of sensorimotor information processing.