Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Autonomic Pathways”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1999

Melanoma cell autonomous growth: the Rb/E2F pathway.

Transformation of normal melanocytes to metastatic melanoma cells is characterized by loss of dependency on external growth factors required for the viability and proliferation of normal melanocytes. The molecular events that lead to melanoma cell autonomous growth are not well defined, but are likely to include sustained activity of cyclin-dependent kinases (CDK2, CDK4 and CDK6) as a result of loss of CDK inhibitors (such as p16INK4a and possibly p27KIP1), and persistent upregulation of several cyclins (cyclin D1, cyclin A and cyclin E), the positive regulators of CDKs. CDKs phosphorylate, and consequently, inactivate the retinoblastoma family of tumor suppressor proteins (pRb, p107 and p130), termed pocket proteins. The inactivation of pocket proteins liberates E2F transcription factors from suppressive complexes ('free' E2F) that, in turn, induces the continuous expression of target genes whose products promote cell cycle progression. In normal melanocytes, external growth factors suppress the activity of all three pocket proteins, allowing E2F activity to accumulate and sustain transcription of target genes required for cell proliferation. In contrast, in melanoma cells from advanced lesions, all three pocket proteins are highly phosphorylated and inactive, even in the absence of environmental mitogens, and free E2F activity is constitutively high. Manipulations of normal mouse melanocytes in vitro, and in vivo in transgenic mouse expressing ectopic genes, further support the notion that growth rate, and release from dependency on external mitogens, positively correlate with inactivation of pocket proteins. The latter has been accomplished by sustained cell surface receptor stimulation, such as constitutive high expression of a growth factor, or by sequestration with dominantly acting viral proteins. Taken together, chronic hyperphosphorlyation/inactivation of pRb, p107 and p130 is probably one of the key events in converting growth-factor dependent normal melanocytes, to autonomously growing melanoma cells. Since all pocket proteins are regulated by CDKs activity, it is likely that agents that inhibit this class of enzymes will be effective in treating melanoma patients.

Animals↗
PubMed2000

Pathway specific expression of neuropeptides and autonomic control of the vasculature.

In this article, we review the immunohistochemical evidence for the pathway-specific expression of co-existing neuropeptides in autonomic vasomotor neurons, and examine the functional significance of these expression patterns for the autonomic regulation of the vasculature. Most final motor neurons in autonomic vasomotor pathways contain neuropeptides in addition to non-peptide co-transmitters such as catecholamines, acetylcholine and nitric oxide. Neuropeptides also occur in preganglionic vasomotor neurons. The precise combinations of neuropeptides expressed by neurons in vasomotor pathways vary with species, vascular bed, and the level within the vascular bed. This applies to both vasoconstrictor and vasodilator pathways. There is a similar degree of variation in the expression of neuropeptide receptors in the vasculature. Consequently, the contributions of different peptides to autonomic vasomotor control are closely matched to the functional requirements of specific vascular beds. This arrangement allows for a high degree of precision in vascular control in normal conditions and has the potential for considerable plasticity under pathophysiological conditions.

Animals↗
PubMedDate not supplied

Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin.

Leptin affects feeding, metabolism, and neuroendocrine status. It is now clearly established that the hypothalamus coordinates these responses, though the specific brain regions engaged by leptin remain unclear. We have used combinations of neuroanatomic techniques to identify candidate pathways in the central nervous system underlying leptin action. Leptin decreases body weight in part by activating the sympathetic nervous system, resulting in increased thermogenesis and energy expenditure. We investigated hypothalamic pathways underlying leptin's effects on stimulating the sympathetic nervous system. We found that leptin activates neurons in the retrochiasmatic area (RCA) and lateral arcuate nucleus (Arc) that innervate the sympathetic preganglionic neurons in the thoracic spinal cord and also contain cocaine- and amphetamine-regulated transcript (CART). We also found that CART neurons in the RCA and the Arc coexpress pro-opiomelanocortin (POMC) mRNA. Recent studies have reinforced the view that the lateral hypothalamic area (LHA) regulates food intake and body weight. Using retrograde tracing with leptin administration, we found retrogradely labeled cells in the Arc contained neuropeptide Y (NPY) mRNA or POMC mRNA. Following leptin administration, NPY cells in the Arc did not express Fos but expressed suppressor of cytokine signaling-3 (SOCS-3) mRNA. In contrast, leptin induced both Fos and SOCS-3 expression in POMC neurons, many of which also innervated the LHA. We suggest that leptin directly activates POMC/CART neurons that project to the LHA, the paraventricular hypothalamic nucleus (PVH), and spinal sympathetic preganglionic neurons. These projections link circulating leptin and neurons that regulate feeding behavior, energy expenditure, and body weight homeostasis.

Animals↗
PubMed1999

Reciprocal circuits involved in nitroglycerin-induced neuronal activation of autonomic regions and pain pathways: a double immunolabeling and tract-tracing study.

This study uses tract-tracing protocols to determine the circuitry of specific nuclei involved in nitroglycerin-induced activation. Combined retrograde and anterograde tracers were injected into nuclei which consistently demonstrate robust Fos expression following our systemic nitroglycerin injection paradigm. The nuclei, which conform to these criteria, that we have evaluated in this study are the locus coeruleus, parabrachial nucleus and paraventricular nucleus of the hypothalamus. Dual Fos/tracer immunocytochemistry in treated animals documented the existence of a subset of autonomic nuclei which are activated by nitroglycerin injection and have reciprocal connections. From the nature of this rich interconnection we suggest that nitroglycerin activates autonomic responses involved in cardiovascular pressor mechanisms. Nuclei which show strong Fos labeling following nitroglycerin administration, but not traced in this study, include the nucleus trigeminalis caudalis and the ventrolateral column of the periaqueductal gray, both of which mediate nociceptive modalities. These data confirm and expand on our previous findings and demonstrate that nitroglycerin activates a complex set of structures that are functionally and structurally interconnected to articulate an integrated response.

Animals↗
PubMed1986

Spontaneous termination of paroxysmal supraventricular tachycardia following disappearance of bundle branch block ipsilateral to a concealed atrioventricular accessory pathway: the role of autonomic tone in tachycardia diagnosis.

We present a case of an 18-year-old man with a history of palpitations in whom episodes of paroxysmal supraventricular tachycardia were easily initiated by administered atrial premature beats. In all 15 control episodes of tachycardia, functional left bundle branch block (LBBB) seen at the onset, resolved within 10-20 cycles (mean, 13.1 +/- 0.95). The tachycardia ended with the normalized QRS complex in each episode. Eleven episodes ended because of block within the antegrade pathway (ended with a P-wave), and four episodes stopped because of block within the retrograde pathway (ended without a P-wave). During the administration of isoproterenol (1 mg/min IV) all six episodes of tachycardia had LBBB but these did not end when LBBB disappeared spontaneously. When LBBB subsided, the mean tachycardia cycle interval shortened from 328.5 +/- 1.4 to 264.2 +/- 2.1 ms (p less than 0.001). Each episode of tachycardia was then terminated by carotid sinus massage. The disappearance of LBBB in control conditions presented the retrograde and antegrade limbs of the reentrant circuit with an early impulse that stopped the tachycardia. After isoproterenol administration, the tachycardia did not end following disappearance of LBBB, thus enabling the tachycardia cycle interval to shorten by a mean of 64.3 +/- 1.9 ms. This extent of tachycardia acceleration is diagnostic of the participation of a concealed, left free-wall bypass tract.

Adolescent↗
PubMed2006

Anatomy of autonomic nerve component in the male pelvis: the new concept from a perspective for robotic nerve sparing radical prostatectomy.

The DaVinci Robot (Intuitive Surgical, Sunnyvale California) with its magnified 3-D vision and multi-jointed wristed instruments enabled us to perform radical prostatectomy with consideration for the pelvic anatomy. In the present paper, we review the pelvic autonomic neuroanatomy with respect to robotic prostatectomy and demonstrate the procedures and critical points of nerve-sparing robotic radical prostatectomy based on novel anatomic concepts. Microscopic and macroscopic data were acquired from 30 fresh and 25 fixed male cadavers. A video study of 205 surgeries was performed for establishing the anatomy relevant to robotic prostatectomy. From a practical standpoint, we could group the relevant neural tissue into three broad zones: (1) proximal neurovascular plate (PNP), (2) predominant neurovascular bundles (PNB), (3) accessory distal neural pathways (ANP). Autonomic ganglion cells existed widely not only in nerve components but also along the viscera. The critical areas of nerve sparing surgery were the distal end of PNP, the entire PNB, and the circumference of the apex. Interindividual differences of cell counts were evident in all sites. Based on these concepts, we established the Athermal Robotic Technique (ART) for nerve sparing prostatectomy. Surgical and oncological outcomes were not mature but feasible. These tri-zonal and ganglion cell concepts may be of benefit to new surgeons undertaking nerve-sparing robotic radical prostatectomy.

Autonomic Pathways↗
PubMed2006

Regulation of salivary gland function by autonomic nerves.

Oral homeostasis is dependent upon saliva and its content of proteins. Reflex salivary flow occurs at a low 'resting' rate and for short periods of the day more intense taste or chewing stimuli evoke up to ten fold increases in salivation. The secretion of salivary fluid and proteins is controlled by autonomic nerves. All salivary glands are supplied by cholinergic parasympathetic nerves which release acetylcholine that binds to M3 and (to a lesser extent) M1 muscarinic receptors, evoking the secretion of saliva by acinar cells in the endpieces of the salivary gland ductal tree. Most salivary glands also receive a variable innervation from sympathetic nerves which released noradrenaline from which tends to evoke greater release of stored proteins, mostly from acinar cells but also ductal cells. There is some 'cross-talk' between the calcium and cyclic AMP intracellular pathways coupling autonomic stimulation to secretion and salivary protein secretion is augmented during combined stimulation. Other non-adrenergic, non-cholinergic neuropeptides released from autonomic nerves evoke salivary gland secretion and parasympathetically derived vasointestinal peptide, acting through endothelial cell derived nitric oxide, plays a role in the reflex vasodilatation that accompanies secretion. Neuronal type, calcium-activated, soluble nitric oxide within salivary cells appears to play a role in mediating salivary protein secretion in response to autonomimetics. Fluid secretion by salivary glands involves aquaporin 5 and the extent to which the expression of aquaporin 5 on apical acinar cell membranes is upregulated by cholinomimetics remains uncertain. Extended periods of autonomic denervation, liquid diet feeding (reduced reflex stimulation) or duct ligation cause salivary gland atrophy. The latter two are reversible, demonstrating that glands can regenerate provided that the autonomic innervation remains intact. The mechanisms by which nerves integrate with salivary cells during regeneration or during salivary gland development remain to be elucidated.

Animals↗
PubMed1985

Separation of the medullo-spinal descending pathway for somatic and autonomic outflow in the cat.

The present study investigated differences between vestibulo-somatic and vestibulo-sympathetic reflexes, along with differences between somatic and autonomic spino-bulbo-spinal (SBS) reflexes in chloralose-urethane anesthetized cats. Electrical stimulation was applied to the vestibular nerve (V) for a duration of 0.3 ms. The potential responses in the sympathetic renal nerve (RN) and somatic lumbar nerve were recorded simultaneously. Responses were recorded for a variety of conditioning stimulus to testing stimulus intervals, and the results were plotted to form a recovery curve. The recovery curve for the test response from the somatic nerve was very different from that of the sympathetic nerve. Following transection of the lateral part of the thoracic cord, in the case of the sympathetic renal nerve, recorded responses were still present on vestibular and lumbar nerve stimulation, whereas in the case of the vestibulo-somatic and somatic SBS reflexes, the reflex response had disappeared after transection. These findings suggest that sympathetic and somatic reactions as a result of vestibular stimulation have different descending pathways in the spinal cord, and that their physiological characteristics are different.

Animals↗
PubMed2005

Sacral neuromodulation in lower urinary tract dysfunction.

Vesico-urethral dysfunction is a major problem in daily medical practice due to its psychological disturbances, its social costs and its high impact on quality of life. Recently, sacral neuromodulation, namely the electrical stimulation of the sacral nerves, appears to have become an alternative for radical bladder surgery particularly in cases of idiopathic bladder overactivity. The mechanism of action is only partially understood but it seems to involve a modulation in the spinal cord due to stimulation of inhibitory interneurons. Temporary sacral nerve stimulation is the first step. It comprises the temporary application of neuromodulation as a diagnostic test to determine the best location for the implant and to control the integrity of the sacral root. If test stimulation is successful, a permanent device is implanted. This procedure is safe in experienced hands. So-called idiopathic bladder overactivity still the major indication for this technique. Patients not likely to benefit from the procedure were those with complete or almost complete spinal lesions, but incomplete spinal lesions seemed to be a potential indication. This technique is now also indicated in the case of idiopathic chronic retention and chronic pelvic pain syndrome. When selection is performed, more than three-quarters of the patients showed a clinically significant response with 50% or more reduction in the frequency of incontinent episodes, but the results vary according to the author's mode of evaluation. From the economic point of view, the initial investment in the device is amortized in the mid-term by savings related to lower urinary tract dysfunction. Finally, this technique requires an attentive follow-up and adjustments to the electric parameters so as to optimize the equilibrium between the neurological systems.

Afferent Pathways↗