Leptin: A Potential Link Between Obstructive Sleep Apnea and Obesity.

Chronic intermittent hypoxia (CIH), a pathophysiological manifestation of obstructive sleep apnea (OSA), is strongly correlated with obesity, as patients with the disease experience weight gain while exhibiting elevated plasma levels of leptin. This study was done to determine whether a relationship may exist between CIH and obesity, and body energy balance and leptin signaling during CIH. Sprague-Dawley rats were exposed to 96 days of CIH or normoxic control conditions, and were assessed for measures of body weight, food and water intake, and food conversion efficiency.

Effect of estrogen on vagal afferent projections to the brainstem in the female.

The effects of 17β-estradiol (E) on the distribution and density of brainstem projections of small or large diameter primary vagal afferents were investigated in Wistar rats using transganglionic transport of wheat germ agglutinin- (WGA; preferentially transported by non-myelinated afferent C-fibers; 2%), or cholera toxin B-subunit- (CTB, 5%; preferentially transported by large myelinated afferent A-fibers) conjugated horseradish peroxidase (HRP) in combination with the tetramethylbenzidine method in age matched ovariectomized (OVX) only or OVX and treated with E (OVX+E; 30 pg/ml plasma) females for 12 weeks. Additionally, these projections were compared to aged matched males. Unilateral microinjection of WGA-HRP into the nodose ganglion resulted in dense anterograde labeling bilaterally, with an ipsilateral predominance in several subnuclei of the nucleus of the solitary tract (NTS) and in area postrema that was greatest in OVX+E animals compared to OVX only and males.

Hypothalamic orexin-A (hypocretin-1) neuronal projections to the vestibular complex and cerebellum in the rat.

Immunohistochemistry combined with retrograde tract-tracing techniques were used to investigate the distribution of orexin-A (OX-A)- and OX-A receptor-like (OX1) immunoreactivity within the vestibular complex and cerebellum, and the location of hypothalamic OX-A neurons sending axonal projections to these regions in the Wistar rat. OX-A immunoreactive fibers and presumptive terminals were found throughout the medial (MVe) and lateral (LVe) vestibular nuclei. Light fiber labeling was also observed in the spinal and superior vestibular nuclei.

Carotid chemoreceptor afferent projections to leptin receptor containing neurons in nucleus of the solitary tract.

Neurons expressing the leptin receptor (Ob-R) exist within the caudal nucleus of the solitary tract (NTS). Additionally, afferent neurons expressing the Ob-R have been identified within the nodose ganglion and NTS. Furthermore, systemic injections or focal injections of leptin directly into NTS potentiate the response of NTS neurons to carotid chemoreceptor activation.

Effects of hypocretin and norepinephrine interaction in bed nucleus of the stria terminalis on arterial pressure.

Forebrain neuronal circuits containing hypocretin-1 (hcrt-1) and norepinephrine (NE) are important components of central arousal-related processes. Recently, these two systems have been shown to have an overlapping distribution within the bed nucleus of the stria terminalis (BST), a limbic structure activated by stressful challenges, and which functions to adjust arterial pressure (AP) and heart rate (HR) to the stressor. However, whether hcrt-1 and NE interact in BST to alter cardiovascular function is unknown.

Co-localization of hypocretin-1 and leucine-enkephalin in hypothalamic neurons projecting to the nucleus of the solitary tract and their effect on arterial pressure.

Experiments were done to investigate whether hypothalamic hypocretin-1 (hcrt-1; orexin-A) neurons that sent axonal projections to cardiovascular responsive sites in the nucleus of the solitary tract (NTS) co-expressed leucine-enkephalin (L-Enk), and to determine the effects of co-administration of hcrt-1 and D-Ala2,D-Leu5-Enkephalin (DADL) into NTS on mean arterial pressure (MAP) and heart rate. In the first series, in the Wistar rat the retrograde tract-tracer fluorogold (FG) was microinjected (50nl) into caudal NTS sites at which L-glutamate (0.25 M; 10 nl) elicited decreases in MAP and where fibers hcrt-1 immunoreactive fibers were observed that also contained L-Enk immunoreactivity.

Evaluation of the Heart and Stroke Foundation of Canada Research Scholarship Program: research productivity and impact.

Objective: To compare the research productivity, and its impact, of individuals awarded research scholarships from the Heart and Stroke Foundation of Canada (HSFC) with that of a parallel group of unsuccessful applicants during the funding years 1980/81 to 1989/90 inclusive. Research productivity was defined as the number of peer reviewed publications, and impact was evaluated from the number of publications cited; the number of citations per publication; the number of citations per individual; and the impact score.

Study Selection: Data were collected on 192 individuals.

Effect of preganglionic stimulation or chronic decentralization on neurotensin-like immunoreactivity in sympathetic ganglia of the cat.

In pentobarbital-anesthetized cats, supramaximal stimulation (40 Hz, 2 h) of the preganglionic input to the acutely decentralized right stellate (RSG) or superior cervical (RSCG) ganglion resulted in a decrease in neurotensin (NT)-like immunoreactivity (IR), by 83% in the SG and by 46% in the SCG, as determined by radioimmunoassay. Chronic (7 days) decentralization of the ganglia resulted in a similar depletion of NT-like IR (SG: 86%; SCG: 76%). Supramaximal stimulation (40 Hz, 2 h) of the intact postganglionic outflow of either ganglion had no effect on NT-like IR.

Organization of ventrolateral medullary afferents to the hypothalamus.

In summary, these anatomical and electrophysiological data have provided evidence to support the suggestion that VLM neurons project directly to regions of the hypothalamus that contain magnocellular neurosecretory neurons. In addition, these results support the suggestion that pathways ascending from the VLM to the hypothalamus function, in part, in the control of the release of the neurohypophyseal hormones by PVH and SON magnocellular neurosecretory neurons during activation of peripheral cardiovascular receptors.

Renal and cardiovascular afferent inputs to hypothalamic paraventriculo-spinal neurons.

Experiments were done in chloralose-anesthetized cats to identify single units in the paraventricular nucleus of the hypothalamus (PVH) that responded to stimulation of afferent renal nerves (ARN) and the buffer nerves (carotid sinus (CSN) and aortic depressor (ADN) nerves), and whose axons projected directly to thoracic spinal sympathetic areas. Of 426 single units tested in the PVH region, 20 were antidromically activated by stimulation of the spinal cord. Sixteen of these antidromic units (80%) responded orthodromically to stimulation of ARN and/or the buffer nerves; 6 units (30%) were excited by ARN stimulation only, 2 units (10%) were excited by both ARN and buffer nerve stimulation, and 6 units were excited and 2 inhibited by buffer nerve stimulation only.

Contribution of paraventricular nucleus to afferent renal nerve pressor response.

Experiments were done in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated cats to determine the effect of afferent renal nerve (ARN) stimulation on the firing frequency of neurons in the paraventricular nucleus of the hypothalamus (PVH), whose axons project directly to the neurohypophysis (NH), and the contribution of these neurons to the pressor response elicited by ARN stimulation. In the first series of experiments, 474 single units were extracellularly recorded in the PVH region. Of these units 86 were antidromically excited by stimulation of the NH.

Neuropeptide and serotonin immunoreactive neurons in the cat ventrolateral medulla.

The distribution of cell bodies containing serotonin (5-HT)-, substance-P (SP)-, neurotensin (NT)-, and somatostatin (SS)-like immunoreactivity (IR) in ventrolateral medulla (VLM) of the cat was studied immunohistochemically after administration of colchicine into the cisterna magna. Perikarya containing 5-HT-, SP-, NT- or SS-IR were found throughout the rostrocaudal extent of the VLM. Although neurons containing the different neuroactive substances appeared to have an overlapping distribution in VLM, some distinct differences were observed.

Distribution and morphology of vasopressin-, neurophysin II-, and oxytocin-immunoreactive cell bodies in the forebrain of the cat.

Experiments were done to provide a detailed map of the location and a description of morphological characteristics of vasopressin (AVP-IR)-, neurophysin II (NII-IR)- and oxytocin (OXY-IR)-immunoreactive neuronal perikarya in the forebrain of the cat. In addition, the location of cells in the forebrain retrogradely labeled following injections of tracers into the neurohypophysis was determined. The distribution of AVP-IR and NII-IR was similar in all cases studied.

Collateral branching in axonal projections to spinal cord from paramedian reticular nucleus neurons.

Experiments were done in cats to identify neurons in the paramedian reticular nucleus (PRN) sending collateral axons to the region of the intermediolateral nucleus (IML) at different levels of the thoracic cord by using lectin-conjugated horseradish peroxidase (HRP) and double-labeling fluorochrome histochemistry to retrogradely label PRN neurons. Injections of Fast blue (FB) into the spinal cord at the T2 level centered in the region of the IML were coupled with injections of Nuclear yellow (NY) into the ipsilateral cord at either the T4 or T7 levels centered in the region of the IML. Neurons in the PRN retrogradely labeled after diffusion of HRP into the region of the IML at the T2 level were observed throughout the rostrocaudal extent of the ventral PRN.

Effect of stimulation of afferent renal nerves on plasma levels of vasopressin.

Experiments were done in alpha-chloralose-anesthetized, paralyzed and artificially ventilated cats with vagus, cervical sympathetic, aortic depressor, and carotid sinus nerves cut bilaterally to investigate the effect of afferent renal nerve (ARN) stimulation on circulating levels of vasopressin (AVP). Electrical stimulation of ARN elicited a pressor response that had two components, a primary (1 degree) component locked in time with the stimulus and a secondary (2 degree) component that had a long onset latency and that outlasted the stimulation period. The 1 degree and 2 degree components of the pressor response were largest at stimulation frequencies of 30 and 40 Hz, respectively.

Central organization of afferent renal nerve pathways.

Although afferent renal nerves have been studied for over a quarter of a century, their physiological role remains unclear. There is considerable experimental evidence indicating that afferent renal nerves convey sensory information from renal receptors to integrative circuits in the central nervous system which gives rise to command signals controlling the function of effector organs. In addition, it has been demonstrated that these integrative neural circuits are found at several different levels of the neuraxis; the spinal cord, the medulla and the hypothalamus.

Function of the ventrolateral medulla in the control of the circulation.

The CNS control of the cardiovascular system involves the coordination of a series of complex neural mechanisms which integrate afferent information from a variety of peripheral receptors and produce control signals to effector organs for appropriate physiological responses. Although it is generally thought that these control signals are generated by a network of neural circuits that are widely distributed in the CNS, over the last two decades a considerable body of experimental evidence has accumulated suggesting that several of these circuits involve neurons found on or near the ventral surface of the medulla oblongata. Neurons in the VLM have been shown to be involved in the maintenance of vasomotor tone, in baroreceptor and chemoreceptor (central and peripheral) reflex mechanisms, in mediating the CIR and somatosympathetic reflexes and in the control of the secretion of vasopressin.

Immunohistochemical identification of noradrenaline- and adrenaline- synthesizing neurons in the cat ventrolateral medulla.

The distribution and morphology of cell bodies containing the catecholamine biosynthetic enzymes dopamine-beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in the ventrolateral medulla (VLM) of the cat were studied immunohistochemically after intracisternal administration of colchicine. Perikarya immunoreactive to DBH were found throughout the VLM extending from approximately the spinomedullary junction to the level of the superior olivary nucleus. In the caudal VLM DBH neurons were found primarily in the region immediately dorsal to the lateral reticular nucleus (LRN), although a few scattered DBH neurons were also found near the ventral surface of the medulla in and around the parvicellular division of the LRN.

Bidirectional cardiovascular connections between ventrolateral medulla and nucleus of the solitary tract.

Single-unit recording experiments were done in chloralose-anesthetized, paralyzed and artificially ventilated cats to identify neurons in ventrolateral medulla (VLM) that send efferent axons directly to the region of the nucleus of the solitary tract (NTS) and receive cardiovascular afferent inputs from the carotid sinus (CSN) and aortic depressor (ADN) nerves and the NTS. Units in VLM were identified by antidromic excitation to stimulation of functionally and histologically verified sites in the NTS complex. Antidromic potentials were recorded from 34 units in VLM.

Lateral hypothalamic and peripheral cardiovascular afferent inputs to ventrolateral medullary neurons.

Experiments were done in chloralose anesthetized, paralyzed and artificially ventilated cats to identify single units in ventrolateral medulla (VLM) projecting directly to the intermediate gray (IG) region of the upper thoracic cord and responding to inputs from pressor sites in the anterior lateral hypothalamus (Hla) and carotid sinus (CSN) and aortic depressor (ADN) nerves. Forty-eight units were antidromically activated in VLM to stimulation of the IG at the level of T2. Of these 48 units, 15 (31%) were orthodromically excited by stimulation of the Hla with a mean latency of 15.

Chemoreceptor and baroreceptor inputs to ventrolateral medullary neurons.

Recording experiments were done in chloralose-anesthetized, paralyzed, and artificially ventilated cats to identify single units in the ventrolateral medulla (VLM) projecting directly to the region of the intermediolateral nucleus of the spinal cord (T2) and responding to selective activation of peripheral chemoreceptors (sodium cyanide, 20-60 micrograms in 0.1-0.3 ml saline into medial thyroid artery) and baroreceptors (phenylephrine, 2 micrograms/kg iv).

Lesions of the paraventricular nucleus alter the development of spontaneous hypertension in the rat.

The role of the paraventricular nucleus of the hypothalamus (PVH) in the development of hypertension was determined after bilateral electrolytic or sham lesions of this structure in 4-5-week-old male spontaneously hypertensive rats (SHR). The average arterial pressure in the PVH-lesioned group was significantly lower compared to sham-lesioned animals during the first 3 weeks after the PVH lesions. At 9 weeks of age the arterial pressures of the PVH-lesioned animals increased, but remained significantly lower than those of the sham-operated animals of the same age.

Paraventricular nucleus of the hypothalamus: an electrophysiological investigation of neurons projecting directly to intermediolateral nucleus in the cat.

Experiments were done in chloralosed, paralyzed and artificially ventilated cats to identify electrophysiologically single units in the paraventricular nucleus of the hypothalamus (PVH) projecting directly to 'cardiovascular' responsive sites in the region of the intermediolateral nucleus (IML) in the upper thoracic cord. Action potentials evoked antidromically by electrical stimulation of the IML were recorded from 41 histologically verified single units in the PVH. Single units responded with a mean latency of 43.

Electrophysiological identification of neurons in ventrolateral medulla sending collateral axons to paraventricular and supraoptic nuclei in the cat.

Experiments were done in chloralosed, paralyzed and artificially ventilated cats to identify single units in the ventrolateral medulla (VLM) that send collateral axons directly to the region of the paraventricular (PVH) and supraoptic (SON) nuclei, and responding to peripheral inputs carrying cardiovascular afferent information. Twenty-six single units were antidromically activated in the VLM to stimulation of both the PVH and SON, and in each case the antidromic potential evoked by stimulation of one site was cancelled by stimulation of the other site. These units responded with latencies corresponding to conduction velocities of 5.