SEARCH · PubMed Health

Results for “Neural Pathways”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 991 records · Page 55Linked to original sources

PubMed1991

Identification of neuronal pathways mediating phototactic modulation of head-waving in Aplysia californica.

The marine mollusc Aplysia californica exhibits a complex, rhythmic motor response, head-waving, in a variety of naturally occurring behavioral contexts. A cellular analysis of this behavior would be greatly facilitated by achieving stimulus control over the response. We have found that such stimulus control can be readily achieved by exposing a head-waving animal to a directional light source, which rapidly elicits a positive phototactic response: the animal either swings its head to face the light or biases its head waving toward the light source. Moreover, we have found that the neural pathways from the principal photoreceptive organs of Aplysia, the eyes and rhinophores, must be intact for the normal execution of this phototactic response: animals with chronic transection of the optic and rhinophore nerves show no phototactic behavior, whereas sham-operated animals continue to exhibit normal phototaxis.

Afferent Pathways↗

PubMed2000

Neural plasticity in the mouse inferior colliculus: relationship to hearing loss, augmented acoustic stimulation, and prepulse inhibition.

C57BL/6J (C57) and DBA/2J (DBA) mice exhibit progressive high-frequency hearing loss. Extracellular recordings of responses of neurons in the inferior colliculus (IC) evoked by 70-dB SPL tones indicated that normal tonotopic organization was greatly disrupted in both strains: still-audible lower frequencies (4-12 kHz) evoked responses in a large percentage of recording sites in ventral tonotopic regions that normally respond strongly to high frequencies only. To relate the IC responses to an auditory behavior, prepulse inhibition (PPI) was measured using 70-dB tones as prepulses. As high-frequency hearing loss progressed in C57 mice, prepulses of 4-12 kHz elicited stronger PPI, and this was significantly correlated with changes in the percentage of IC recording sites responding to 70-dB tones (the neural pathway for PPI includes the IC). The analysis was extended to DBA mice that had been exposed to an augmented acoustic environment (AAE) - a procedure that improves PPI. In these mice, a higher percentage of IC recording sites responded to 70-dB tones, and this was correlated with improved PPI. The data suggest that responses of IC neurons reflect both hearing loss-induced plasticity and changes induced by exposure to an AAE, and these neural changes are correlated with the magnitude of PPI.

Acoustic Stimulation↗

PubMed1989

Hypothalamic noradrenergic and sympathoadrenal control of glycemia after stress.

Central noradrenergic pathways play a significant role in mediating blood glucose levels after neuroglycopenia. To further investigate hypothalamic noradrenergic neuronal activity (NNA) and sympathoadrenal influences in glucoregulation, we studied the effects of acute stress on glycemia and insulin release in normal and adrenalectomized (ADRX) rats. Within 5 min of exposure of rats to ether or cold-swim stress, significant positive correlations were evident between hypothalamic NNA and serum glucose levels (r = 0.70, P less than 0.001; at 15 min r = 0.78, P less than 0.0001). Five minutes after stress in the intact rat, insulin release was inhibited and serum insulin levels inversely correlated to hypothalamic NNA (r = 0.45, P less than 0.05). This relationship between insulin and NNA was no longer present 15 min after stress, but the levels of insulin remained inappropriately low with respect to the elevated serum glucose levels (approximately 30% above basal). Blockade of sympathetic noradrenergic pathways by treatment of intact rats with guanethidine prevented the rise in glucose after cold-swim stress but did not prevent the inhibition of insulin release. Fifteen minutes after exposure of ADRX rats to cold-swim stress their hypothalamic NNA and serum glucose levels were similar to intact animals. However, in contrast to their intact counterparts, serum insulin levels were significantly elevated (P less than 0.01). These data are consistent with central noradrenergic neural pathways directly mediating hepatic glucose release and indirectly inhibiting pancreatic insulin release via activation of adrenal medullary catecholamines.

Adrenalectomy↗

PubMed2003

Melanogenesis in the ink gland of Sepia officinalis.

Among the various melanin-producing systems, the ink gland of the cuttlefish (Sepia officinalis) has traditionally been regarded as a most convenient model system for the studies of melanogenesis. The ink gland is a highly specialized organ with immature cells in the inner portion, from where the cells gradually mature, migrate towards the outer portion of the gland and become competent to produce melanin giving rise to particulate melanosomes. When cell maturation is complete, melanin is secreted into the lumen of the gland, accumulated into the ink sac and ejected on demand. Biochemical studies carried out over the past two decades have shown that the ink gland contains a variety of melanogenic enzymes, including tyrosinase, a peculiar dopachrome rearranging enzyme (which catalyses the rearrangement of dopachrome to 5,6-dihydroxyindole) and a peroxidase (presumably involved in the later stages of melanin biosynthesis). These enzymes are functionally interactive in close subcellular compartments of ink gland cells and appear to act in a concerted fashion during the process of melanogenesis in the mature portion of the gland. More recent studies have revealed that ink production and ejection are affected and modulated by the N-methyl-D-aspartate (NMDA)-nitric oxide (NO)-cyclic GMP (cGMP) signalling pathway. Glutamate NMDA receptor and NO synthase, the enzyme responsible for the synthesis of NO, have been detected by biochemical and immunohistochemical techniques in immature ink gland cells. Stimulation of NMDA receptors caused a marked elevation of cGMP levels, activation of tyrosinase and increased melanin synthesis in the mature portion of the gland, via the NO-guanylyl cyclase interaction. This signalling is also present in different regions of the nervous system in Sepia and in certain neural pathways controlling contraction of the ink sac sphincters and wall muscle in the ejection mechanism. Overall, these and other findings allowed elaboration of an improved model of melanin formation in Sepia, which underscores the complex interplay of melanogenic enzymes and regulatory factors, highlighting both the similarities and the differences with melanogenesis in mammals.

Animals↗

PubMed1981

Mediation of the ocular response to cyclocryocoagulation.

The possible roles of prostaglandins and a neural pathway in the disruption of the blood-aqueous barrier in the rabbit eye after cyclocryocoagulation were studied. Both the preoperative IV administration of the prostaglandin inhibitor acetylsalicylic acid and the application of retrobulbar and topical anesthesia reduced IOP and decreased breakdown of the blood-aqueous barrier, as measured by protein in the aqueous humour. These results imply that the acute response of the animal eye to cyclocryocoagulation is mediated partly by prostaglandins and partly by a neural component resistent an inhibitor of prostaglandin synthesis. When administered together, acetylsalicylic acid and ocular anesthesia yielded a further reduction in postoperative reactions and protein concentrations in the aqueous humour, but were unable to abolish the ocular response completely. The dual ocular mediation to cyclocryocoagulation is apparently due to the combined thermal and mechanical injury caused to ocular structures which synthesize prostaglandins and receive sensory innervation from the trigeminal nerve. The considerable breakdown of the blood-aqueous barrier in cyclocryocoagulation allows leakage of different molecular weight proteins, in equal ratio, into the aqueous humour.

Animals↗

PubMed1984

Role of the hypothalamic paraventricular nucleus in neuroendocrine responses to daylength in the golden hamster.

Daylength regulates reproduction in golden hamsters through a mechanism which involves the pineal indoleamine, melatonin. Retinal input to the suprachiasmatic nucleus of the hypothalamus (SCN) and sympathetic innervation of the pineal are critical to the inhibition of reproduction by short photoperiods. Since the hypothalamic paraventricular nucleus (PVN) receives extensive input from the SCN in the rat, and may influence autonomic function via its brainstem and spinal cord projections, we studied the role of this nucleus in photoperiodically induced gonadal regression in the hamster. Bilateral electrolytic destruction of either the paraventricular nucleus (PVN) or suprachiasmatic nucleus (SCN) of the hypothalamus completely blocked testicular regression induced by either blinding or exposure to short days (10L:14D). Lesions in the retrochiasmatic hypothalamus (RCA) which may have interrupted the pathway of previously identified efferents from the SCN to the PVN were also effective in preventing short day-induced gonadal regression. Pineal melatonin content was measured in intact and lesioned hamsters sacrificed 3-5 h before lights on, at the time of the expected nocturnal peak. While SCN and RCA lesions significantly reduced pineal melatonin content, PVN lesions were still more effective in this regard. We conclude that the hamster's neuroendocrine response to photoperiod is mediated by neural pathways which include retinohypothalamic input to the SCN and efferents from this nucleus to the PVN which travel dorsocaudally through the retrochiasmatic area of the hypothalamus. Effectiveness of lesions restricted to the PVN suggests that direct projections from the PVN to spinal autonomic centers convey photoperiodic information which regulates pineal, and hence gonadal, function.

Animals↗

PubMed1991

Functional recovery and collateral neuronal sprouting examined in young and aged rats following a partial neural lesion.

The rat pineal gland was chosen as a model system to study how aging affects the capacity of surviving neurons to compensate for partial destruction of a neural pathway. The pineal gland receives bilateral overlapping sympathetic innervation from the two internal carotid nerves, whose activity regulates several aspects of pineal metabolism in a circadian fashion. The most dramatic of these is the marked nighttime increase in the activity of N-acetyltransferase, the rate-limiting enzyme in melatonin synthesis. These features allow for the pineal gland to be used as a model system for studies on neuronal plasticity, since it is possible to create specific partial neural lesions and to evaluate functional recovery subsequently at the cellular level. We examined the activity of N-acetyltransferase and the content of melatonin in the pineal gland as indices of pineal function at various time points after unilateral surgical denervation (lesion of one of the two internal carotid nerves) in 4-month-(young) and 25-month-old (aged) rats. At both ages, the nighttime levels of the two parameters were significantly lower 8 h after this lesion than in sham-operated animals of the same age, indicating impaired function. When examined at later time points (i.e., 1.5 and 10 days after this lesion), both young and aged animals exhibited full recovery in these two parameters. Measurement of specific neuronal uptake of [3H]norepinephrine was utilized as an index of the number of sympathetic varicosities innervating the pineal gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed2003

Motor evoked potentials from the pelvic floor.

AIMS: Proper function of the lower urinary tract depends on the integrity of the central and peripheral nervous pathways on multiple levels, and the complexity of this system leaves it susceptible to even minor lesions. While dysfunction of the lower urinary tract is prevalent amongst patients with nervous system disease, e.g., multiple sclerosis (MS), most women with lower urinary tract dysfunction (LUTD) have no overt neurological cause. Refined neuro-diagnostic approaches are needed to reveal neurogenicity in these patients. A potential method is transcranial magnetic stimulation (TMS), which is used routinely to test the motor innervation of limb muscles, but also can be applied to test pelvic floor efferents. To resolve the lack of methodological clarity and the need for normative values for the use of pelvic floor motor evoked potentials (MEPs), 30 healthy women and 16 women with MS were studied. METHODS: The healthy women underwent MEP studies with various stimulus and recording modalities, and, to test reproducibility, 18 of them were retested at a separate session. The women with MS underwent MEP testing as well as urodynamic studies. RESULTS: From the methodological studies of healthy women, the use of invasive concentric needle electrodes was found to be superior to surface electrodes. When applying magnetic stimuli over the sacral region, various methodological problems were encountered. In the healthy women, a large variability of responses was noted, the long-term reproducibility of pelvic floor MEP latencies was poor, and in some cases responses could not be obtained. In the study of women with MS, prolonged central conduction times were found, along with many cases of unevokable responses, and a poor correlation of MEPs to urodynamic findings. The problems of obtaining selective recordings from the inaccessible pelvic floor musculature are discussed, and possible sources of variability in MEPs from the pelvic floor are considered. By relating the findings in the present studies to those of others using different modalities, some reflections are presented on the nature of the neural pathways to the pelvic floor activated by magnetic stimulation. As unevokable responses from the pelvic floor were an occasional finding among the healthy women, it is argued that a pelvic floor non-response in a patient with suspected corticospinal lesion should be interpreted with care, and should not carry the same clinical significance as an absent limb response. CONCLUSIONS: The inherent limitations of pelvic floor MEPs are discussed, and it is concluded that while there seems to be only limited clinical value of pelvic floor MEP testing, there might be some interesting scientific perspectives in studies that aim to control and explain the variability of responses.

Adult↗

PubMed2000

Multiple central nervous system targets for eliciting beneficial effects on memory and cognition.

The development of drugs for the treatment of disorders of cognition has benefited from a more precise knowledge of the loss of specific neural pathways associated with certain neurodegenerative diseases such as Alzheimer's disease (AD). The loss of basal forebrain cholinergic neurons in AD has engendered the development of new compounds that target various aspects of the cholinergic system. However, limitations in the effectiveness of the most common of these, the anticholinesterases, have fueled the race to provide more efficacious compounds. In an attempt to avoid side effects and improve efficacy, other neuronal targets have been considered, including receptors for norepinephrine, dopamine, serotonin, excitatory amino acids, neural peptides, and others. Our laboratory has had the opportunity to study the memory-enhancing potential of many of the compounds developed expressly for these neuronal targets in macaques. Upon reviewing 21 such studies it was evident that: 1) To varying degrees, pharmacological manipulation of each target yielded improved task performance. 2) Combining pharmacological targets could lead to additive or synergistic effects on task performance. 3) Mature adult and aged monkeys provided equivalent estimates of drug effectiveness. 4) There appeared to be no limiting level of task improvement for compounds tested in aged and younger monkeys. 5) Certain of these agents also exhibited potential disease-modifying actions. Thus, certain memory-enhancing agents may prove more useful when implemented early in the course of a disease such as AD, and they also may enjoy a wide application for the treatment of the memory decline associated with normal aging.

Aging↗

PubMed1993

Sex pheromone systems in goldfish: comparisons to vomeronasal systems in tetrapods.

Most amphibians, reptiles and mammals possess a well defined dual olfactory system comprised of separate neural pathways that regulate different olfactory functions. One pathway originates in the nasal cavity and gives rise to what is commonly referred to as the main olfactory system. The other pathway originates in the vomeronasal organ (VNO) and gives rise to the accessory olfactory system. Functionally, the main olfactory system is thought to subserve, olfactory-mediated tasks such as feeding and grooming, while the accessory olfactory system is believed to be primarily involved in mediating behavioral and physiological responses to sex pheromones. Traditionally, it has been difficult to address whether teleosts possess any components of the vomeronasal system, since they generally do not meet the criteria used to identify vomeronasal systems in other vertebrates. Previous conclusions that the nasal epithelia of fish is olfactory and not vomeronasal in nature are based on observations that teleosts lack a separate VNO-like chemosensory structure and an anatomically distinct accessory olfactory bulb. However, because sex pheromones have been identified in the goldfish, it is now possible to compare the neural substrates that regulate pheromone-induced responses in teleosts to those that mediate similar responses in other vertebrates. The olfactory system in goldfish is particularly well suited for such comparisons, because it comprises anatomical and functional subdivisions that resemble those associated with the main and accessory olfactory systems in tetrapods. The olfactory pathways that mediate endocrine and behavioral responses to sex pheromones in goldfish are described and then compared to the main and accessory olfactory systems of tetrapods. In making these comparisons, a number of similarities become apparent. First, the olfactory pathways that regulate responses to sex pheromones in goldfish are different from those that serve a more general olfactory function. Second, these functional differences appear to be subserved by separate and anatomically distinct olfactory tract projections to the brain. Third, the lateral olfactory tracts and their central projections in goldfish appear to serve a function analogous to that of the main olfactory system, while the medial olfactory tracts and their central projections comprise a pathway remarkably similar to the vomeronasal-accessory olfactory system. These findings suggest that teleosts may possess functional correlates of tetrapod vomeronasal systems, but in a form that has yet to be recognized. If so, medial olfactory tract projections in goldfish may be evolutionarily conserved and expressed in tetrapods as the vomeronasal system, or the medial olfactory tract projections may be new pathways that have evolved to serve the same function.

Animals↗

PubMed2003

Lumbar spinal stenosis in the elderly: an overview.

Lumbar spinal stenosis is a common condition in elderly patients and also one of the most common reasons to perform spinal surgery at an advanced age. Disc degeneration, facet degeneration and hypertrophy, and ligamentum flavum hypertrophy and calcification usually participate in the genesis of a stenotic condition in the elderly. These changes can lead to symptoms by themselves or decompensate a preexisting narrow canal. Although some lesions are more central or more lateral, this classic dichotomy is less present in the elderly patient, in whom the degenerative process usually encroaches both central and lateral pathways. Some less common causes of lumbar spinal stenosis are found in the aging subject, such as Paget's disease. However, it must be stressed that so-called stenotic images (sometimes severe) are present on imaging studies in a great number of symptom-free individuals, and that the relationship between degenerative lesions, importance of abnormal images, and complaints is still unclear. Lumbar stenosis is a very common reason for decompressive surgery and/or fusion. Various conditions can lead to a narrowing of the neural pathways and differential diagnosis with vascular troubles, also common in the elderly, can be challenging. The investigation of stenotic symptoms should be extremely careful and thorough and include a choice of technical examinations including vascular investigations. This is of utmost importance, especially if a surgical sanction is considered to avoid disappointing results.

Aged↗

PubMed1969

Types of nervous activity which may be recorded from the carotid sinus nerve in the sheep foetus.

1. In the sinus nerve of mature foetal sheep (120-147 days gestational age) three types of nerve activity have been demonstrated: (a) baroreceptor afferent, in which the nerve activity was synchronous with the pulse pressure wave and which followed pressure changes in the carotid sinus including those caused by compressing the umbilical cord. The discharge of nine out of twelve baroreceptor afferents increased with sympathetic stimulation, (b) a subtype of (a) in which there was irregular activity from pressure receptors which most probably represented baroreceptors discharging at or about threshold, and (c) in the older foetuses (130-147 days), there was activity which was unaffected by changes in carotid sinus pressure, P(a, O2) or NaCN but which increased in discharge rate with compression of the umbilical cord or with stimulation of the cervical sympathetic; this activity then increased with injection of NaCN and was thus identified as chemoreceptor in origin. In addition, a pathway originating in the cervical sympathetic and which passed through the superior cervical ganglion was demonstrated by evoking a compound action potential on stimulation of the preganglionic cervical sympathetic nerve.2. Recordings from pre- or post-ganglionic cervical sympathetic nerves showed that spontaneous activity was present and increased when the umbilical cord was compressed.3. These results suggest that the carotid body chemoreceptors in the foetus are relatively insensitive to chemical changes and that, in their activation at birth, the sympathetic could be involved. Possible neural pathways and the mechanism of activation are discussed.

Action Potentials↗

PubMed2001

The role of neuroeffector mechanisms in the pathogenesis of asthma.

Neural regulation of the airways consists of cholinergic excitatory, adrenergic inhibitory nerves and nonadrenergic, noncholinergic (NANC) nerves. NANC nerves can be either inhibitory or excitatory. Cholinergic nerves form the predominant bronchoconstrictor neural pathway in human airways. Acetylcholine controls neuronal and nonneuronal target cells via a short-lived action at nicotinic and muscarinic receptors. The most important control over acetylcholine release from postganglionic cholinergic nerves is exerted by acetylcholine itself. The M2 autoreceptor is located prejunctionally on postganglionic nerves. Its stimulation limits the further release of acetylcholine. A loss of function in the neuronal muscarinic M2 autoreceptor occurs after exposure to allergen, ozone, or viruses. In human airways, inhibitory NANC (i-NANC) mechanisms are the only neural bronchodilatory mechanisms. The presumed neurotransmitters of the i-NANC system are vasoactive intestinal peptide and nitric oxide. Substance P and neurokinin A have been implicated as the neurotransmitters mediating the excitatory part of the NANC nervous system. NK2 receptors are present on smooth muscle of both large and small airways and mediate part of the bronchoconstrictor effect of tachykinins. Most of the proinflammatory effects of substance P are mediated by the NK1 receptor. Tachykinin receptor antagonists are currently being developed as a possible anti-asthma treatment. An extensive cross-talk exists between nerves and the immune system. The complexity of the picture has increased further as it has become clear that classical neurotransmitters, such as acetylcholine and neuropeptides, are produced by nonneuronal cells.

Animals↗

PubMed2003

Emerging antiobesity drugs.

The healthcare burden that the obesity epidemic now poses in highly significant, in part due to increased risk of secondary chronic diseases such as hypertension. A lack of physical activity and high fat diets are major factors contributing to this condition. However, increasingly apparent is the genetic predisposition of individuals and ethnic groups to obesity. Present treatment strategies are currently inadequate and unlikely to have a major effect on the future prevalence of obesity. To slow the obesity epidemic, the source needs to be tackled now through fundamental research into the mechanisms by which obesity is manifest, and education on the risks and how to prevent it. This article will describe current and emerging treatments for obesity and review the recent advances in research that may provide the antiobesity treatments of the future. Research into obesity has escalated at considerable pace, catalysed by the discovery of the obese gene product leptin. Leptin is secreted by adipose tissue and acts via specific receptors in the brain to engage central neural pathways involved in regulating energy homeostasis. Since this discovery, numerous significant advances have been made in our understanding of how the brain integrates and responds to central and peripheral signals involved in maintaining energy homeostasis, and how disruption of these signalling mechanisms can manifest as obesity. As a consequence of these findings, numerous potential sites for therapeutic intervention into this condition have and are materializing. The aim of this review is to highlight current treatment strategies for obesity, recent advances in our understanding of the central neural control of energy balance, and what the authors consider to be the most promising targets for the development of novel antiobesity drugs in the future. Thus, the review focuses on leptin, neuropeptide Y, melanocortin and ghrelin signalling at the level of the CNS, and strategies targeting the sympathetic innervation of fat cells at the periphery.

Animals↗

PubMed1994

Extrapancreatic cholinergic nerves mediate cholecystokinin-stimulated pancreatic polypeptide release.

Although vagal cholinergic stimulation is the predominant regulatory mechanism governing the release of pancreatic polypeptide (PP), recent studies suggest that cholecystokinin (CCK) is also an important mediator. The present study examined the role of cholinergic neural pathways in the PP response to exogenous CCK-8 using a selectively denervated canine pancreas model. Chronic denervated pancreatic preparations were created in five dogs, while five dogs underwent sham laparotomy as controls. On study days, the fasted animals were infused intravenous CCK-8 (40 or 400 pmole/kg/hr) for 60 min both with and without atropine (20 micrograms/kg/hr). Plasma was collected at 20-min intervals and PP levels were determined by radioimmunoassay. CCK-8 elicited a dose-dependent increase in circulating PP in dogs with a neurally intact pancreas. Atropine and pancreatic denervation eliminated the PP response to CCK-8 at 40 pmole/kg/hr (P < 0.01) and inhibited the PP response to CCK-8 at 400 pmole/kg/hr (P < 0.05). The high dose of CCK-8 still elicited a small PP response in the denervated dogs (P < 0.05), which was subsequently abolished by the addition of atropine. These findings suggest that extrapancreatic cholinergic nerves are essential components of CCK-stimulated PP release, and that intrapancreatic cholinergic activity may play a limited role.

Animals↗

PubMed1994

Hypoglossal and phrenic responses to central respiratory inhibition in piglets.

Neonatal apnea is characterized by decreased neural output to the ventilatory muscles, and frequently associated with upper airway obstruction. We sought to characterize: (1) the role of central chemosensitive structures at the ventral medullary surface (VMS) in modulating hypoglossal and phrenic neural output, and (2) the recovery of hypoglossal and phrenic neural output during simulated central apnea. We studied 14 anesthetized, paralyzed, ventilated piglets aged 14-21 days and performed VMS cooling to inhibit central neural pathways mediating CO2 sensitivity. Phrenic and hypoglossal ENGs and end-tidal CO2 were continuously recorded. During CO2 rebreathing, hypoglossal activity was always more sensitive than phrenic activity to the inhibitory effects of VMS cooling. When phrenic apnea was induced by VMS cooling, and followed by discontinuation of ventilation for 60 sec in order to induce simultaneous hypercapnia and hypoxia, reappearance of hypoglossal ENG was delayed and recovery was significantly suppressed when compared to phrenic ENG. Therefore, attenuated central chemosensitivity during early postnatal life appears to preferentially inhibit neural output responsible for upper airway patency, and may predispose to upper airway obstruction during recovery from neonatal apnea.

Animals↗

PubMed2004

Methionine adenosyltransferase:adrenergic-cAMP mechanism regulates a daily rhythm in pineal expression.

(S)-adenosylmethionine (SAM) is a critical element of melatonin synthesis as the methyl donor in the last step of the pathway, the O-methylation of N-acetyl 5-hydroxytryptamine by hydroxyindole-O-methyltransferase. The activity of the enzyme that synthesizes SAM, methionine adenosyltransferase (MAT), increases 2.5-fold at night in the pineal gland. In this study, we found that pineal MAT2A mRNA and the protein it encodes, MAT II, also increase at night, suggesting that the increase in MAT activity is caused by an increase in MAT II gene products. The night levels of MAT2A mRNA in the pineal gland were severalfold higher than in other neural and non-neural tissues examined, consistent with the requirement for SAM in melatonin synthesis. Related studies indicate that the nocturnal increase in MAT2A mRNA is caused by activation of a well described neural pathway that mediates photoneural-circadian regulation of the pineal gland. MAT2A mRNA and MAT II protein were increased in organ culture by treatment with norepinephrine (NE), the sympathetic neurotransmitter that stimulates the pineal gland at night. NE is known to markedly elevate pineal cAMP, and here it was found that cAMP agonists elevate MAT2A mRNA levels by increasing MAT2A mRNA synthesis and that drugs that block cAMP activation of cAMP dependent protein kinase block effects of NE. Therefore, the NE-cAMP dependent increase in pineal MAT activity seems to reflect an increase in MAT II protein, which occurs in response to cAMP-->protein kinase-dependent increased MAT2A expression. The existence of this MAT regulatory system underscores the importance that MAT plays in melatonin biogenesis. These studies also point to the possibility that SAM production in other tissues might be regulated through cAMP.

Animals↗

PubMed1996

Use of the novel carbocyanine tracer fast-DiI for investigating upper respiratory tract cranial nerves in prenatal rats.

The use of traditional neuroanatomic tracing methods with tracers such as horseradish peroxidase requires living systems to take up and transport the label. These tracers have limited application in the study of prenatal systems. The advent of the carbocyanine dye DiI provided a tool by which neuronal pathways may be traced in postmortem fixed tissue. This dye allows careful dissection of prenatal organisms and specific application of the tracer to the neuroanatomic structure under investigation. Although DiI has become increasingly popular, it is limited by the difficulty in applying crystals to peripheral nerves and in the lengthy trace times, particularly in fixed tissue. A chemically modified version of DiI has been introduced that may overcome some of the limitations in using this tracer. The newer dye, fast-DiI, is easy to apply and can trace neural pathways in a shorter period. We describe our experience with the use of fast-DiI in the prenatal rat for the investigation of motoneurons that subserve upper respiratory tract structures. We have determined protocols for fixation, application of dye, processing of tissue, and visualization of traces. The entire protocol can be completed within 1 week, and the use of fast-DiI is easy to learn and apply. The resultant labeling of traced nerves is specific and clearly demonstrates respective motor nuclei and individual motoneurons.

Animals↗