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THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS. I. VIRUS PATHWAYS TO THE NERVOUS SYSTEM OF SUCKLING MICE DEMONSTRATED BY FLUORESCENT ANTIBODY STAINING.

The pathogenesis of herpes simplex virus encephalitis and myelitis was studied in suckling mice using routine titration procedures and fluorescent antibody staining for the identification of infected cells. After intracerebral inoculation virus was shown to disperse rapidly in the cerebrospinal fluid (CSF), multiply in meninges and ependyma, and then invade the underlying parenchyma infecting both neurons and glia. Following extraneural inoculation virus gained access to the central nervous system (CNS) by both hematogenous and neural pathways. After intraperitoneal and intranasal inoculation virus was found to multiply in viscera and produce viremia; foci of CNS infection then developed around small cerebral vessels. After subcutaneous and intranasal inoculation neural spread of virus was demonstrated along corresponding peripheral and cranial nerves. This spread resulted from the centripetal infection of endoneural cells (Schwann cells and fibroblasts). Antigen was not found in axons even after infection of the corresponding ganglion cell perikaryon. Subsequent spread within the CNS was unrelated to neural tracts, and there was no evidence of axonal spread of virus in the host-virus system studied. These findings are discussed in relation to previous and current theories of the viral "blood-brain barrier" and neural pathways of infection.

Animals↗

Sensory reinnervation of a musculocutaneous flap: an experimental rabbit study.

Sensory neurotisation of a muscle (sensory nerve transfer to the motor nerve of a muscle) produces muscle sensibility, but not skin sensibility. How to achieve sensation of a musculocutaneous flap remains a challenge to reconstructive microsurgeons. The purpose of our study was to determine if multiple nerve grafts which were placed vertically between the neuromuscular entrance zone of a muscle and a target area of dermis on the overlying skin could improve sensation. Thirty-six gracilis musculocutaneous flaps (18 rabbits) were raised and divided into three groups: group 1 consisted of 12 sensory neurotised gracilis musculocutaneous flaps with five nerve grafts each; group 2 consisted of another 12 sensory neurotised gracilis flaps with 10 nerve grafts each; and the control group consisted of 12 sensory neurotised gracilis musculocutaneous flaps without any nerve grafts. All nerve grafts spanned the distance between the neuromuscular entrance zone of the gracilis muscle and a specified 3 cm diameter area of the skin island. The saphenous nerve (sensory) was coapted to the obturator nerve (motor nerve of the gracilis) in an effort to achieve improved sensation of the skin island in the musculocutaneous flaps. After 6 months, the flaps were individually evaluated using cortical somatosensory evoked potentials (CSSEP) using normal, painful, cold and hot stimuli. One unoperated rabbit was studied as the baseline CSEEP for comparison. Retrograde horseradish peroxidase (HRP) labelling was then performed to evaluate the possibility of newly established neural pathways. Results of the CSSEP testing revealed that flaps possessing 10 nerve grafts (group 2) demonstrated better sensation when compared to flaps possessing five nerve grafts (group 1) or no nerve grafts (control group). Furthermore, retrograde HRP labelling proved that a new neural pathway had been established from the skin island to the dorsal root ganglia of S1 and S2 via the interposed nerve grafts and the sensory neurotised gracilis muscle in groups 1 and 2 rabbits. The control group did not display any sensory regeneration.

Animals↗

Novel Notch alleles reveal a Deltex-dependent pathway repressing neural fate.

BACKGROUND: The Notch receptor triggers a wide range of cell fate choices in higher organisms. In Drosophila, segregation of neural from epidermal lineages results from competition among equivalent cells. These cells express achaete/scute genes, which confer neural potential. During lateral inhibition, a single neural precursor is selected, and neighboring cells are forced to adopt an epidermal fate. Lateral inhibition relies on proteolytic cleavage of Notch induced by the ligand Delta and translocation of the Notch intracellular domain (NICD) to the nuclei of inhibited cells. The activated NICD, interacting with Suppressor of Hairless [Su(H)], stimulates genes of the E(spl) complex, which in turn repress the proneural genes achaete/scute. RESULTS: Here, we describe new alleles of Notch that specifically display loss of microchaetae sensory precursors. This phenotype arises from a repression of neural fate, by a Notch signaling distinct from that involved in lateral inhibition. We show that the loss of sensory organs associated with this phenotype results from a constitutive activation of a Deltex-dependent Notch-signaling event. These novel Notch alleles encode truncated receptors lacking the carboxy terminus of the NICD, which is the binding site for the repressor Dishevelled (Dsh). Dsh is known to be involved in crosstalk between Wingless and Notch pathways. CONCLUSIONS: Our results reveal an antineural activity of Notch distinct from lateral inhibition mediated by Su(H). This activity, mediated by Deltex (Dx), represses neural fate and is antagonized by elements of the Wingless (Wg)-signaling cascade to allow alternative cell fate choices.

Adaptor Proteins, Signal Transducing↗

Dyspnea.

Dyspnea is the medical term for the patient's or subject's complaint of shortness of breath. It encompasses the respiratory discomfort experienced in many different diease states as well as the shortness of breath felt by a normal subject during or after strenuous exercise. Several parameters which have been shown to correlate with the onset or severity of dyspnea are described, including reduced vital capacity, the ratio of minute ventilation to vital capacity, reduced breathing reserve, the work of breathing, and the oxygen cost of breathing. Attempts at quantitation of dyspnea have usually consisted of measuring physiological parameters associated with the sensation, such as the "dyspneic index". The direct measurement of respiratory sensations using modern psycho-physical methods is at an early stage of development. Since the observation that the existence of dyspnea is often unrelated to any disturbance of arterial blood gas composition, it has been generally held that the mechanism of dyspnea is primarily neurophysiological. The neural pathways may conceptually be divided into those which transmit the "dyspnea message" from the respiratory apparatus to integrating centers in the brain, and those concerned with subsequently bringing the sensation to the level of consciousness. It seems likely that there is no single sensing mechanism and neural pathway which will be able to explain dyspnea in the diverse populations of patients and subjects who experience unpleasant respiratory sensations. Three theories concerning mechanisms of dyspnea are briefly described: "length-tension inappropriateness", vagal afferent activity especially from the J-receptors, and the recent concept of diaphragmatic fatigue. Some specific characteristics of the shortness of breath experienced in certain disease states are described, including chronic bronchitis and emphysema, bronchial asthma, pulmonary fibrosis and congestive heart disease.

Asthma↗

Reflex cardiorespiratory effects of nociceptive oesophageal distension in the decerebrate rat.

It is well established that painful distension of hollow viscera such as the oesophagus can evoke a reflex tachycardia and pressor response; however, the nature of the oesophageal afferent pathway(s) remains controversial. This study investigated the afferent arc which mediates these reflex cardiovascular changes in the decerebrate rat. In addition, the effect of oesophageal distension on the respiratory activity of the costal diaphragm was studied. Focal distension of the oesophagus (volume of 0.3 ml applied for 10 s) just above the diaphragmatic hiatus evoked a reproducible pressor response and tachycardia in the decerebrate rat. Respiration was transiently inhibited at the beginning of oesophageal distension and prior to the rise in blood pressure. Neuromuscular blockade with the nicotinic acetylcholine receptor blocker alpha-bungarotoxin (140 microg bolus) had no effect on the magnitude of the cardiovascular response. Therefore the efferent supply to the striated muscle of the rat oesophagus was not essential in mediating this reflex. Signal averaging of the mean blood pressure response showed that neither selective ablation of oesophageal spinal afferents nor bilateral vagotomy altered the early trajectory of the pressure response. Bilateral vagotomy reduced the peak magnitude of the response to sustained oesophageal distension. In contrast, selective removal of spinal afferents had no effect on the response. Ablation of both neural pathways was essential to abolish the reflex cardiovascular and respiratory responses. It can be concluded that both vagal and spinal afferent pathways are utilised in the reflex cardiorespiratory response to painful oesophageal distension. Although ablation of one neural pathway had no effect on the response it was still implicated in the reflex, since ablation of both pathways was necessary to prevent the cardiorespiratory changes. This study emphasises the need for caution when inferences are made concerning single selective ablations of multiply innervated organs.

Animals↗

Enhanced activation of reward mediating prefrontal regions in response to food stimuli in Prader-Willi syndrome.

BACKGROUND: Individuals with Prader-Willi syndrome (PWS) exhibit severe disturbances in appetite regulation, including delayed meal termination, early return of hunger after a meal, seeking and hoarding food and eating of non-food substances. Brain pathways involved in the control of appetite in humans are thought to include the hypothalamus, frontal cortex (including the orbitofrontal, ventromedial prefrontal, dorsolateral prefrontal and anterior cingulate areas), insula, and limbic and paralimbic areas. We hypothesised that the abnormal appetite in PWS results from aberrant reward processing of food stimuli in these neural pathways. METHODS: We compared functional MRI blood oxygen level dependent (BOLD) responses while viewing pictures of food in eight adults with PWS and eight normal weight adults after ingestion of an oral glucose load. RESULTS: Subjects with PWS demonstrated significantly greater BOLD activation in the ventromedial prefrontal cortex than controls when viewing food pictures. No significant differences were found in serum insulin, glucose or triglyceride levels between the groups at the time of the scan. CONCLUSIONS: Individuals with PWS had an increased BOLD response in the ventromedial prefrontal cortex compared with normal weight controls when viewing pictures of food after an oral glucose load. These findings suggest that an increased reward value for food may underlie the excessive hunger in PWS, and support the significance of the frontal cortex in modulating the response to food in humans. Our findings in the extreme appetite phenotype of PWS support the importance of the neural pathways that guide reward related behaviour in modulating the response to food in humans.

Adult↗

Extrinsic innervation of the cat prostate gland: a combined tracing and immunohistochemical study.

PURPOSE: The purpose of the present study was to determine the peripheral neural pathways, spinal distribution, sizes, and peptide transmitter content of primary afferent and autonomic efferent neurons that innervate the prostate gland. METHODS: Retrograde transport of the fluorescent dye "fast blue" (injected into the prostate gland) was combined with neurotransmitter immunohistochemistry. Lesions of the pelvic and pudendal nerve were used to determine the peripheral neural pathways. RESULTS: The majority of the afferent innervation arose from the sacral dorsal root ganglia (DRG) and was equally comprised of small, substance P- and calcitonin gene-related peptide-immunoreactive (IR) neurons and large, non-IR neurons. The majority (70%) of the afferent axons traversed the pelvic nerve with the remainder traversing the pudendal nerve. Fewer afferent neurons were located in lumbar DRG; nearly all of these were small, peptidergic neurons. Efferent autonomic neurons were located in the inferior mesenteric ganglia (IMG), sympathetic chain ganglia (SCG), and pelvic plexus ganglia (PPG). Nearly all efferent neurons in the IMG and SCG, but only 2/3 of the PPG neurons, contained dopamine-beta-hydroxylase. Substantial neuropeptide Y innervation was derived from the SCG but not the IMG or PPG. CONCLUSIONS: First, clinical reports suggested that sensory innervation of the prostate would be purely nociceptive in nature (implied by small, peptide-IR neurons). However, the present study suggests that there may also be a substantial, presumably non-nociceptive, afferent innervation (implied by findings of large, non-IR neurons). Second, 3 sources of autonomic efferent innervation exist, each being different in the distribution of transmitter phenotypes. Understanding the physiological role of putative non-nociceptive primary afferent neurons, and the differential roles of the various autonomic neurons, is likely to be important in developing therapies for the treatment of prostatic diseases, such as benign prostatic hyperplasia and prostatodynia.

Amidines↗

Theta burst stimulation of the human motor cortex.

It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices. With its relevance to processes such as learning and memory, the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models. To date, the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation (rTMS), a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp. However, effects on synaptic plasticity reported are often weak, highly variable between individuals, and rarely last longer than 30 min. Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable, consistent, long-lasting, and powerful effect on motor cortex physiology and behavior after an application period of only 20-190 s.

Adult↗

The importance of the hypothalamic lateral retrochiasmatic area in the control of adrenocorticotropin and thyrotropin secretion.

Anterolateral hypothalamic deafferentiation was made in rats to explore the importance of the neural pathways through the lateral retrochiasmatic area (RCAL) in the regulation of ACTH and TSH secretion. In rats with complete bilateral RCAL transection, pituitary-adrenal function was altered in the following respects compared to sham-operated controls. 1) Basal plasma ACTH, corticosterone (B), and adrenal weight were depressed. 2) Plasma ACTH and B elevation in response to 3-min ether inhalation were markedly decreased or abolished. 3) Insulin-induced hypoglycemia produced no or little plasma B elevation. 4) Lysine-vasopressin was significantly less effective in inducing pituitary-adrenal activation. Reductions in plasma ACTH and B concentrations and adrenal weight were correlated with the completeness of the RCAL transection. The plasma TSH concentration was lower in the deafferented rats than in the controls regardless of the completeness of the cut at the RCAL, indicating that the neural pathways traversing this area do not possess a critical importance for the regulation of TSH if the rest of the hypothalamus is deafferented anterolaterally. We conclude that intact neural connections between the medial basal hypothalamus and the central nervous system at the RCAL are essential for the maintenance of normal hypothalamic-pituitary-adrenal function.

Adrenal Glands↗

Seasonal regulation of neuroendocrine activity in male Turkish hamsters (Mesocricetus brandti): role of the hypothalamic paraventricular nucleus.

Male Turkish hamsters received horizontal knife cuts within the hypothalamus to investigate the role of afferent and efferent projections of the paraventricular nucleus (PVN) in seasonal regulation of endocrine function. Following surgery, the animals were exposed to either a long (16 h light/8 h dark) or a short (8 h light/16 h dark) photoperiod. Similar to pinealectomy, knife cuts placed ventral to the PVN, so as to disrupt transfer of photic information to the pineal gland, resulted in a rapid decline in circulating prolactin (PRL) and follicle-stimulating hormone (FSH) levels, as well as a reduction in testicular size, under both long- and short-photoperiod conditions. In contrast, knife cuts placed just dorsal to the PVN, 50 as to leave connections to the pineal gland intact, did not prevent the effects of short-day exposure on PRL secretion; however, short-day induced declines in FSH levels and testicular size were largely prevented by these lesions. The present results are consistent with past findings that the integrity of the neural pathway to the pineal gland is necessary for the maintenance of appropriate reproductive responses to photoperiod in seasonal mammals. They further indicate a dissociation between the role of hypothalamic connections in the photoperiod-dependent secretion of two anterior pituitary hormones, i.e., PRL and FSH, and suggest that release of these hormones may depend upon different neural pathways for their expression.

Afferent Pathways↗

Sensorimotor state of the contralateral leg affects ipsilateral muscle coordination of pedaling.

The objective of this study was to determine if independent central pattern generating elements controlling the legs in bipedal and unipedal locomotion is a viable theory for locomotor propulsion in humans. Coordinative coupling of the limbs could then be accomplished through mechanical interactions and ipsilateral feedback control rather than through central interlimb neural pathways. Pedaling was chosen as the locomotor task to study because interlimb mechanics can be significantly altered, as pedaling can be executed with the use of either one leg or two legs (cf. walking) and because the load on the limb can be well-controlled. Subjects pedaled a modified bicycle ergometer in a two-legged (bilateral) and a one-legged (unilateral) pedaling condition. The loading on the leg during unilateral pedaling was designed to be identical to the loading experienced by the leg during bilateral pedaling. This loading was achieved by having a trained human "motor" pedal along with the subject and exert on the opposite crank the torque that the subject's contralateral leg generated in bilateral pedaling. The human "motor" was successful at reproducing each subject's one-leg crank torque. The shape of the motor's torque trajectory was similar to that of subjects, and the amount of work done during extension and flexion was not significantly different. Thus the same muscle coordination pattern would allow subjects to pedal successfully in both the bilateral and unilateral conditions, and the afferent signals from the pedaling leg could be the same for both conditions. Although the overall work done by each leg did not change, an 86% decrease in retarding (negative) crank torque during limb flexion was measured in all 11 subjects during the unilateral condition. This corresponded to an increase in integrated electromyography of tibialis anterior (70%), rectus femoris (43%), and biceps femoris (59%) during flexion. Even given visual torque feedback in the unilateral condition, subjects still showed a 33% decrease in negative torque during flexion. These results are consistent with the existence of an inhibitory pathway from elements controlling extension onto contralateral flexion elements, with the pathway operating during two-legged pedaling but not during one-legged pedaling, in which case flexor activity increases. However, this centrally mediated coupling can be overcome with practice, as the human "motor" was able to effectively match the bilateral crank torque after a longer practice regimen. We conclude that the sensorimotor control of a unipedal task is affected by interlimb neural pathways. Thus a task performed unilaterally is not performed with the same muscle coordination utilized in a bipedal condition, even if such coordination would be equally effective in the execution of the unilateral task.

Adult↗

Why do asthmatic subjects respond so strongly to inhaled adenosine?

Bronchospasm induced by adenosine is blocked by representatives of all the major classes of drugs used in the treatment of asthma. Understanding the mechanism of this bronchospasm may help understand the way these drugs work. Clinical studies have suggested involvement of neural pathways, mast-like cells and mediators such as histamine, serotonin and lipoxygenase products. There is a strong link between responsiveness to adenosine and eosinophilia. In different animal models A1, A2b and A3 adenosine receptor subclasses have all been implicated in inducing bronchospasm. whilst occupation of the A2a receptor generally has no, or the opposite effect. At least two different mechanisms, both involving neural pathways, exist. One, involving the adenosine A1 receptor, functions in mast cell depleted animals; the other requires interaction with a population of mast-like cells activated over A2b or A3 receptors. Not only histamine but also serotonin and lipoxygenase products released from the mast-like cells are potential mediators. In animal models good reactivity to adenosine receptor agonists is generally only found when the animals are first sensitized and exposed to allergen in ways likely to induce an allergic inflammation. An exception is the BDE rat, which reacts to adenosine receptor agonists such as APNEA or NECA even without allergen exposure. This rat strain does however show evidence of spontaneous eosinophilic inflammation in the lung even without immunization. As mast cells both release adenosine and respond to adenosine, adenosine provides a non-specific method of amplifying specific signals resulting from IgE/antigen interaction. This mechanism may not only have a pathological significance in asthma; it may be part of a normal bodily defense response that in asthmatic subjects is inappropriately activated.

Adenosine-5'-(N-ethylcarboxamide)↗

Binaural cross-correlation and auditory localization in the barn owl: a theoretical study.

The barn owl is a nocturnal predator that is able to capture mice in complete darkness using only sound to localize prey. Two binaural cues are used by the barn owl to determine the spatial position of a sound source: differences in the time of arrival of sounds at the two ears for the azimuth (interaural time differences (ITDs)) and differences in their amplitude for the elevation (interaural level differences (ILDs)). Neurophysiological investigations have revealed that two different neural pathways starting from the cochlea seem to be specialized for processing ITDs and ILDs. Much evidence suggests that in the barn owl the localization of the azimuth is based on a cross-correlation-like treatment of the auditory inputs at the two ears. In particular, in the external nucleus of the inferior colliculus (ICx), where cells are activated by specific values of ITD, neural activation has been recently observed to be dependent on some measure of the level of cross-correlation between the input auditory signals. However, it has also been observed that these neurons are less sensitive to noise than predicted by direct binaural cross-correlation. The mechanisms underlying such signal-to-noise improvement are not known. In this paper, by focusing on a model of the barn owl's neural pathway to the optic tectum dedicated to the localization of the azimuth, we study the mechanisms by which the ITD tuning of ICx units is achieved. By means of analytical examinations and computer simulations, we show that strong analogies exist between the process by which the barn owl evaluates the azimuth of a sound source and the generalized cross-correlation algorithm, one of the most robust methods for the estimate of time delays.

Journal Article↗

Neuronal activity and information processing in motor control: from stages to continuous flow.

Some years ago, we proposed, along with others, that the isomorphism between models of information processing by stages and the organization of neural pathways connecting functionally specialized neuronal networks was a guideline for conducting experiments in which the integration of methods and concepts of cognitive psychology and of neurophysiology was a promising approach to increase our knowledge of the processes responsible for motor control. At a time when models of serially organized information processing stages are being increasingly challenged, the deciphering of the underlying brain processes increasingly suggests that current views about the linkage between neural structures and behavioural functions must be reconsidered. First, at the "molar" level, the notion of a functional specialization of neuronal networks as, for example, being "sensory", "sensorimotor" or "motor", has to be viewed as a quantitative and not as a qualitative concept. Second, at the "molecular" level, the notion of a clear-cut functional differentiation between neuronal units, or between small sets of neurons, must similarly be revised: a neuron may be more or less "sensory" or "motor" and, moreover, may share both these functional properties to varying degrees. When the brain processes responsible for movement control are reconsidered in the light of these two concepts--that is a functional heterogeneity of structurally defined neuronal networks, as well as a continuum in functional specification of isolated neuronal units--data collected by using single-cell recording of neuronal activity fit well into the model of a continuous flow of information processing: neural pathways from the cortical parietal association areas to the corticospinal apparatus appear as a privileged sensorimotor information stream along which the amount of neuronal activity responsible for movement planning progressively decreases, while the amount of neuronal activity involved in movement execution progressively increases.

Animals↗

Evidence for regulation of peptide-YY release by the proximal gut.

Peptide-YY (PYY) is a novel enteric peptide that is structurally related to pancreatic polypeptide and neuropeptide-Y. The objectives of the present experiments were to characterize the following aspects of PYY metabolism: the distribution of PYY in the canine gastrointestinal tract, the release of PYY in response to oral ingestion of a mixed meal or intraduodenal (ID) administration of oleic acid, the effect of ileocolectomy on the release of PYY in response to ID administration of oleic acid when transit of chyme to the distal ileum and colon is prevented, the effect of interruption of intramural neural pathways of the small bowel on the release of PYY, and the effect of iv cholecystokinin on the release of PYY. The results of these experiments demonstrate that PYY immunoreactivity is distributed primarily in the terminal ileum, colon, and rectum. Circulating levels of PYY increase significantly (P less than 0.05) within 10-30 min after ingestion of a meal or to ID administration of a fatty acid. Complete interruption of the flow of chyme to the site of PYY-containing cells (i.e. ileum-colon) did not block the release of PYY; however, ileocolectomy abolished the release of PYY in response to ID administration of oleic acid. Severance of intramural neural pathways along the small bowel did not alter the release of PYY in response to an oral meal. Intravenous administration of graded doses of cholecystokinin stimulated the release of PYY in a dose-related manner. The results of these experiments indicate that the release of PYY from the distal ileum and colon is controlled, at least in part, by an extramural neural, endocrine, or a combination of both types of mechanisms which originate in the foregut.

Animals↗

Identification of specific pathways of communication between the CNS and NK cell system.

The specific signals and pathways utilized by the natural killer (NK) cell system and the central nervous system (CNS) that results in the conditioned response (CR) is not clearly understood. Single trial conditioning of the NK cell activity provides us with a model to probe the mechanisms of communication between two major systems (Immune and CNS) which are involved in the health and disease of the individual. The studies show that the IFN-beta molecules possess the properties attributed to the unconditioned stimulus (US). IFN-beta can penetrate the CNS and evoke the elevation of NK cell activity in the spleen. This unconditioned response (UR) can be linked to a specific conditioned stimulus (CS). Specific odors such as camphor provide a neural pathway for the CS to associate with the US. Evidence is presented that in conditioning there are two locations where memory develops. The CS/US association is made centrally and its memory is stored at a central location, but the memory for the specificity of the odor is presumably stored in the olfactory bulbs. The CS recalls the CR by triggering the olfactory neural pathway which, in turn, signals the hypothalamic-pituitary axis to release mediators that modulate the activity of NK cells in the spleen. These results imply that through conditioning one has direct input into the regulatory hypothalamus that controls the internal environment of the organism and the health and disease of the individual. Consequently, it is not inconceivable that through this approach we might be able to alter the course of a disease process.

Animals↗

2-Deoxy-D-glucose and mercaptoacetate induce different patterns of macronutrient ingestion.

2-Deoxy-D-glucose (2DG) and mercaptoacetate (MA) are antimetabolic agents that reduce the metabolism of glucose and fatty acids, respectively, and stimulate feeding. The present study compared the effects of MA and 2DG on macronutrient self-selection. Because 2DG and MA have different metabolic actions and appear to activate different neural pathways, our hypothesis was that 2DG and MA would elicit different patterns of macronutrient selection. The first experiment examined macronutrient selection in response to 2DG, MA, and 0.9% saline in rats maintained on a three-macronutrient self-selection diet consisting of cornstarch, casein, and vegetable oil. Subsequently, one macronutrient source was replaced in each of three similar experiments with Polycose, albumin, or solid vegetable shortening. Finally, 2DG and MA tests were conducted in which only one macronutrient (cornstarch, casein, or oil) was available during the test. Results show that MA and 2DG elicit different macronutrient preferences. 2DG elicits intake of all three macronutrients in the same relative proportion consumed during spontaneous feeding across a number of dietary conditions, suggesting that glucoprivation activates interoceptive signals and neural pathways similar to those involved in normal hunger. MA elicits a selective intake of protein. Conditions in which carbohydrate palatability is enhanced or protein palatability is diminished lead to a relative increase in carbohydrate intake in response to MA. However, MA did not increase the intake of fat. Results suggest that intake of each macronutrient is subject to separate neural or endocrine control, and that these controls are linked to metabolic cues.

Animals↗

Neural immune pathways and their connection to inflammatory diseases.

Inflammation and inflammatory responses are modulated by a bidirectional communication between the neuroendocrine and immune system. Many lines of research have established the numerous routes by which the immune system and the central nervous system (CNS) communicate. The CNS signals the immune system through hormonal pathways, including the hypothalamic-pituitary-adrenal axis and the hormones of the neuroendocrine stress response, and through neuronal pathways, including the autonomic nervous system. The hypothalamic-pituitary-gonadal axis and sex hormones also have an important immunoregulatory role. The immune system signals the CNS through immune mediators and cytokines that can cross the blood-brain barrier, or signal indirectly through the vagus nerve or second messengers. Neuroendocrine regulation of immune function is essential for survival during stress or infection and to modulate immune responses in inflammatory disease. This review discusses neuroimmune interactions and evidence for the role of such neural immune regulation of inflammation, rather than a discussion of the individual inflammatory mediators, in rheumatoid arthritis.

Animals↗