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PubMed2003

Auditory startle response in cervical dystonia.

The excitability of brainstem neurons is abnormally enhanced in patients with cervical dystonia (CD), but the extend of such abnormality is not known. We examined whether patients with CD showed abnormalities in the auditory startle response (ASR), a brainstem reflex elicited by an unexpected loud stimulus. Thirteen patients with CD were investigated 3 months after botulinum toxin treatment. Thirteen healthy volunteers served as controls. ASRs were elicited by binaural high-intensity auditory stimuli. Reflex electromyographic (EMG) activity was recorded simultaneously with surface electrodes bilaterally from masseter, orbicularis oculi, sternocleidomastoid, and biceps brachii muscles. We found that ASR onset latencies were similar for patients and controls. CD patients had significantly lower ASR probabilities than controls (P = 0.007). ASR area under the curve was significantly smaller in CD patients (P = 0.017). Similar to controls, patients showed a significant habituation of ASR (P < 0.001, each); however, CD patients showed a prolonged tonic or phasic EMG activity after the initial ASR that was not observed in controls. Normal latencies and recruitment pattern indicate a preserved organization of intrinsic neural pathways mediating ASR in CD. Reduced ASR probability and magnitude as well as prolonged EMG activity after the proper startle response corroborate and extend previous findings on brainstem dysfunction in CD.

Adult↗

PubMed1995

Fate of the upper urinary tract in multiple sclerosis.

Urologic problems are a major source of morbidity for patients with multiple sclerosis (MS). Fifty-four to 78% of patients experience bladder symptoms which are due to spinal lesions interrupting neural pathways that control micturition. MS patients could have upper or lower motor neuron lesion type bladders. Both obstructive and irritative symptoms may be present. Although lower urinary tract dysfunction has been well described in MS, few studies have investigated the fate of the upper urinary tract. Thirty-two patients with MS were referred for urodynamic evaluation. Twenty-six of the 32 patients had upper urinary tract studies performed. Only 1 of the 26 patients had evidence of upper urinary tract deterioration. It is our impression that upper tract deterioration occurs infrequently in these patients. We discuss clinical clues that may predict deterioration.

Adult↗

PubMed1995

Reduced variance of latencies in pudendal evoked potentials after normalization for body height.

The value of the Somatosensory Evoked Potentials (SEP) in the assessment and detection of neurological disorders could be considerably enhanced if the normative standards of (SEP) characteristic parameters were normalized taking into account all other systematic sources of variance. The present study examines the influence of body height on the peak and interpeak latencies of the pudendal somatosensory evoked potentials. We examined the peak latency (L1) of the evoked potential recorded at the L1 vertebra and the onset latency (ONc) of the cortical evoked potentials, after stimulation of the pudendal nerve, as a function of body height in 40 normal male subjects (age 20-40 years). Significant positive correlation was found between both (ONc) latency and ONc-L1 interpeak latency and body height (H). Assuming that the latter is proportional to the length of the neural pathways, the experimental data were fitted using a theoretical model representing the conduction in the sensory neuraxis as a function of body height. Using the estimated fitting functions, we normalized our data with regard to a typical value of body height. The normalized values of the aforementioned latencies reveal a significantly reduced variance, as compared to the original ones, and consequently their diagnostic importance is significantly increased. Similar procedures applied to the L1 (spinal) latencies and the latencies of the bulbocavernosus reflex (BCR) reveal no correlation with body height and this is discussed on the basis of neuroanatomical considerations.

Adult↗

PubMed1995

Irritable bladder syndrome in an animal model: a continuous monitoring study.

Irritable bladder syndrome (IBS) was induced in four female African green monkeys (Cercopithecus aethiops) by the use of intravesical instillation of acetone. The animals were housed in a modified metabolic cage for continuous micturition monitoring, and two uroflowmeters connected to a remote PC monitored the frequency, voided volumes, and peak flows. Before and after, urea absorption studies and urodynamics were obtained for each animal. Urea absorption increased significantly after acetone instillation and returned to baseline after 4 weeks (26 to 66 to 32%). Intravesical acetone instillation produced marked effects on bladder physiology in the first week. Bladder compliance dropped from a baseline of 10.47 to 0.58 ml/cm H2O. The voiding pattern changed from a normal pattern with a mean voided volume of 17.58 ml into marked increase in frequency and dribbling pattern with few voids (mean = 5.03 ml). Systematic behavioral observations were carried out for 4 hours per day utilizing an observation program on a laptop computer. Activity patterns, attention, sterotypic behaviors, and self-directed activities were recorded for each monkey. The animals demonstrated decreased frequency of activity and increased frequency in self-directed activities (groom, scratch), behaviors consistent with an animal experiencing pain or discomfort. The findings suggested that IBS induction in monkeys is feasible and produces a clinical picture similar to interstitial cystitis in humans. It offers a suitable animal model to enhance the understanding of voiding dysfunction with its neural pathways and to test the different therapeutic modalities to control IBS.

Acetone↗

PubMed2007

Autonomous contractile activity in the isolated rat bladder is modulated by a TRPV1 dependent mechanism.

AIMS: Resiniferatoxin (RTX), a vanilloid compound and agonist of the transient receptor potential channel 1 (TRPV1), is known for its beneficial effects on neurogenic detrusor overactivity. The mainstream rationale for its use is the desensitization of TRPV1 on sensory bladder afferents. However, recent findings showed that TRPV1 is present in other cell types in the bladder. To eliminate the effects of RTX on spinal and central neural circuits, we investigated autonomous contractility in normal and neurogenic rat bladders after treatment with RTX. METHODS: Female Wistar rats were made paraplegic at vertebral level T8-T9. Animals were intravesically pre-treated with vehicle (ethanol 5%) or RTX (100 nM) and sacrificed after 72 hr. Each bladder was excised and placed in a heated organ bath, where intravesical pressures were measured. Effects on contractile parameters of intravesical volume load, the non-selective muscarinic receptor agonist carbachol (CA) and electrical stimulation (ES) of nerves were studied in both groups. RESULTS: In RTX-treated normal bladders we found shorter contractions with higher amplitude than in control bladders (P < 0.05). In RTX-treated neurogenic bladders the amplitude and duration of autonomous contractions were increased compared with controls (P < 0.05). Furthermore RTX induced an increased response to CA and to ES (P < 0.05). CONCLUSIONS: RTX significantly affected the properties of autonomous bladder contractile activity. This provides evidence for local effects of RTX on bladder contractile activity, which are not mediated by afferent neural pathways and which may contribute to the beneficial effects on detrusor overactivity. TRPV1 and TRPV1(+) cells seem to play an important role in (autonomous) bladder contractility.

Animals↗

PubMed2004

Of lasers, mutants, and see-through brains: functional neuroanatomy in zebrafish.

Behavioral functions are carried out by localized circuits in the brain. Although this modular principle is clearly established, the boundaries of modules, and sometimes even their existence, are still debated. Zebrafish might offer distinct advantages in localizing behaviors to discrete brain regions because of the ability to visualize, record from, and lesion precisely identified populations of neurons in the brain. In addition, genetic screens in zebrafish enable the isolation of mutations that disrupt neural pathways and/or behaviors, as an alternative lesioning technique with complementary strengths to laser ablations. For example, the Mauthner cell, a large identified neuron in the hindbrain, has been postulated to be both necessary and sufficient for the execution of escapes. We discuss in this review how experiments, using laser ablations, calcium imaging, and mutants have eroded this notion. Even in a simple behavior, such as escape, many parallel pathways appear to be involved with no single one being absolutely necessary. Lesion studies and the analysis of behavioral mutants are now also beginning to elucidate the functional architecture of the zebrafish visual system. Although still in an embryonic stage, the neuroanatomy of behaviors in zebrafish has a bright future.

Animals↗

PubMed1985

Evidence for octopaminergic modulation of an insect visceral muscle.

Two dorsal unpaired median neurons (DUMOV1 and DUMOV2) lying in the posterior region of the VIIth abdominal ganglion of Locusta migratoria have axons which project to the muscles of the oviducts. This study reports the presence of octopamine within isolated DUMOV cell bodies, as well as in the oviducal nerve and innervated oviducal muscle. Individual cell bodies were pooled and found to contain about 0.34 pmol of octopamine per cell body giving an approximate value of 1.27 mM octopamine. Octopamine is concentrated within the area of oviducal muscle which receives DUMOV axons. Pharmacological studies reveal that the amplitude of neurally-evoked contractions of the oviducal muscle is reduced in a dose-dependent manner by octopamine, with threshold lying between 5 X 10(-10) M and 7 X 10(-9) M. The receptors for this response show a specificity for octopamine and synephrine, with an order of potency being octopamine = synephrine greater than metanephrine greater than tyramine greater than dopamine. The presence of octopamine throughout this neural pathway, coupled with the demonstration of octopaminergic modulation of muscular contraction, supports the hypothesis that octopamine serves a physiological role in this visceral system.

Animals↗

PubMed1993

Neuroblastoma: the result of multistep transformation?

Genetic and molecular abnormalities, in association with malignant phenotypes, have been previously demonstrated in a variety of human tumors. Although the multistep theory fits well for some cancers such as retinoblastoma and colon carcinoma, for many others it still remains to be proven. Neuroblastoma, a tumor found in pediatric patients, seems to fall into the multistep model. Nonrandom chromosome abnormalities have been found with 1p deletion, loss of heterozygosity for short arm of chromosome 1 and for chromosome 11q and 14q. Amplification of N-myc oncogene and an increased level of Ras protein have also been demonstrated. Therefore, even if it is not possible to show that these mutations happen as discrete events in their order of appearance, the multistep model seems involved in neuroblastoma development. Neuroblastoma has a peculiar aspect, however, that makes this tumor a natural model of defect of cell differentiation. In fact, there is a particular subset of metastatic tumors that show spontaneous regression. In vitro, neuroblastoma cell lines can be induced to differentiate along the neural pathway using retinoic acid. Other natural and chemical substances are also able to induce cell differentiation. During retinoic acid treatment, N-myc oncogene expression decreases and other genes are deregulated. p53 and MDR1 gene expression increases. These two different aspects, failure of cell differentiation pathway and genetic mutations, make the neuroblastoma one of the most difficult problems of modern molecular biology.

Apoptosis↗

PubMed1989

Acute effects of alprazolam and adinazolam on the concentrations of corticotropin-releasing factor in the rat brain.

Corticotropin-releasing factor (CRF) is the major physiological regulator of the hypothalamic-pituitary-adrenal (HPA) axis. However, considerable evidence indicates that CRF may be responsible for integrating not only the endocrine, but the autonomic and behavioral responses of an organism to stress as well. In addition, clinical studies indicate that CRF of both hypothalamic and extrahypothalamic origin may be hypersecreted in major depression as well as other psychiatric disorders. These findings, taken together, led to the hypothesis that the efficacy of antidepressant and/or anxiolytic drugs may be related to their actions on CRF-containing neural pathways in the central nervous system (CNS). Therefore, alterations of CRF concentrations in 18 rat brain regions were studied after acute administration of a tricyclic antidepressant (imipramine) or one of two triazolobenzodiazepines (alprazolam or adinazolam) that possess anxiolytic properties typical of benzodiazepines, as well as purported antidepressant activity unique to these compounds. Treatment with alprazolam or adinazolam increased hypothalamic CRF concentrations, which was associated with lower plasma ACTH concentrations. In contrast, the concentration of CRF was markedly reduced in the locus coeruleus, amygdala, and several cortical regions by either triazalobenzodiazepine. Acute treatment with imipramine was without effect on CRF concentrations in any brain region studied. Of particular interest is the finding that the two triazolobenzodiazepines exert effects on CRF concentrations in the locus coeruleus and hypothalamus that are opposite to CRF changes seen after stress.

Alprazolam↗

PubMed1996

Electrophysiology of the circumventricular organs.

Since the first anatomical description of the circumventricular organs (CVOs) as a structurally distinct group of regions in the central nervous system (CNS), considerable information has implicated these structures as physiologically significant autonomic control centers located at the blood-brain interface. Specialized features of these structures, such as their extensive vasculature, lack of the normal blood-brain barrier (BBB) (i.e., capillaries have a fenestrated endothelium), and dense aggregations of a variety of peptidergic receptors, support an involvement of the CVOs in communication between the circulation and the CNS. The two best understood examples of CVOs with the ability to sense circulating substances impermeable to the BBB are the subfornical organ (SFO) and the area postrema (AP). Specifically, the ability of numerous peptides to influence CNS function, as the result of actions on the neural substrate of these structures has been especially well documented. Considerable anatomical, biochemical, pharmacological, and physiological evidence has implicated these structures as CNS sites at which angiotensin (ANG), atrial natriuretic peptide (ANP), vasopressin (VP), and endothelin (ET) act to influence neuroendocrine and other more classical autonomic functions. In the following sections, we review neurophysiological studies which have provided new and exciting insights regarding the specific neural pathways and cellular mechanisms through which CVO neurons are able to exert their profound influences over central autonomic control.

Animals↗

PubMed1998

Ontogeny of the photoperiodic control of prolactin and luteinizing hormone secretion in male and female bantams (Gallus domesticus).

The development of the photoperiodic responses for prolactin and luteinizing hormone (LH) secretion was determined in the bantam (Gallus domesticus), which becomes somatically mature at 16-18 weeks of age. Male and female bantams were reared from hatch on short days (8 h light/day) and photostimulated by transfer to 20 h light/day at 4, 8, 12, and 16 weeks. Photostimulation at all ages stimulated a robust increase in prolactin secretion in both sexes. Luteinizing hormone secretion was also stimulated except in 4-week-old females and 16-week-old males. It is concluded that the neural pathways involved in the photoperiodic control of LH and prolactin secretion are mature in juvenile bantams well before somatic maturity.

Aging↗

PubMed1996

A new proposal for radical hysterectomy.

OBJECTIVE: The authors revised the surgical procedure for radical hysterectomy utilizing detailed observation of the venous system, connective fascial sheets, and neural pathways within the uterine supports. STUDY DESIGN: The anterior, middle, and posterior uterine supports were reclassified into two systems, supporting or fascial and drainage or areoral. Supporting system consisted of the superficial layer of the vesicouterine ligament, fascial part of the Mackenrodt ligament, sacrouterine ligament, and rectovaginal ligament, whereas drainage system consisted of the deep layer of the vesicouterine ligament, vascular part of the Mackenrodt ligament, and the so-called mesoureter. The operative procedure was planned according to the continuity of these ligaments and executed first by excising the fascia and then dissecting the denuded areoral tissue. RESULTS: Among the 15 patients who underwent surgery for uterine cancer during a 2-year period the mean (SD) time required for the operation was 305.5 +/- 30.5 min and the mean (SD) total volume of blood loss 592.0 +/- 238.2 ml. A mean (SD) period of 14.3 +/- 3.8 postoperative days was required until the volume of the residual urine decreased to less than 50 mL. CONCLUSION: The present operation has been structured more three-dimensionally and systematically than before. Further, safety of the operation was significantly improved including prevention of hemorrhage and preservation of bladder function.

Female↗

PubMed1994

Hormonal regulation of opioid peptide neurons in the anteroventral periventricular nucleus.

Steroid hormones provide a means of coordinating the activity of widespread neural systems that mediate endocrine, autonomic, and somatomotor aspects of reproductive processes that are essential for the propagation of mammalian species. Because these processes are quite different in each sex, the neural pathways that control them are also sexually differentiated. The anteroventral periventricular nucleus (AVPV) of the preoptic region occupies a nodal point in sexually dimorphic forebrain circuits and appears to play a critical role in regulating gonadotropin secretion. The AVPV contains sexually dimorphic populations of opioid peptide containing neurons that display different patterns of development and are differentially regulated in adult animals by gonadal steroids. Moreover, estrogen (ER) and progesterone (PR) receptors are expressed in AVPV neurons in a transmitter-specific way, and the expression of these nuclear transacting factors is differentially regulated by sex steroids. Thus, neurons in the AVPV show distinct patterns of hormonal regulation of gene expression, and distinct hormone receptor profiles.

Animals↗

PubMed1996

Hormonal responses to parental and nonparental conditions in male cotton-top tamarins, Saguinus oedipus, a New World primate.

The socially monogamous cotton-top tamarin (Saguinus oedipus) monkey is a cooperative breeder with the breeding male providing extensive parental care shortly after birth. We examined the relationship of urinary prolactin and cortisol excretion both to male parental care and as a stress response in the cotton-top tamarin monkey. First-morning urine samples were collected to determine hormonal concentrations. Hormonal and behavioral data were collected on 8 male cotton-top tamarins during the 2 weeks before and the 2 weeks following birth of infants to their mate, 11 nonparental males with exposure to females, and three eldest sons from large family groups. Prolactin levels were significantly higher in experienced fathers during the postpartum period than in the other males, while cortisol levels were significantly lower in experienced fathers and eldest sons. Prolactin levels in experienced fathers were consistently elevated before birth, following birth, and after infants were weaned; prolactin levels during times of infant independence were still significantly higher than those in nonfather males. First-time fathers exhibited prolactin levels that were significantly higher after the births of infants than these same males did when they were paired with nonpregnant females. Elevated prolactin concentrations also occurred prior to the first birth, suggesting that males may be receiving cues from their pregnant females. The elevated prolactin levels in parental males may be associated with the experience of the fathers. Correlation between prolactin levels and number of successful births, number of previous births, and age were high. The care of newborn infants did not appear to be a stressful event since cortisol levels were not elevated postpartum. Both cortisol and prolactin were elevated following capture and injection of saline or a dopaminergic receptor antagonist, indicating that prolactin does respond to acute stress. Cortisol levels did not coincide with prolactin levels except under acute stress conditions, suggesting that different neural pathways are probably involved in prolactin release during parental care versus acute stress. These studies provide evidence that male urinary prolactin levels may be elevated due to cues from pregnant females and the constant exposure of males to the family environment.

Animals↗

PubMed1996

Testosterone control of male-type sexual behavior in the tammar wallaby (Macropus eugenii).

In the tammar wallaby, Macropus eugenii, the expression of male-type sexual behavior is apparently determined by the activating effects of testicular hormones in adulthood. The incidence of male-type copulatory behavior and sexual checking behavior was compared in intact (control) males, control females, testosterone-treated females, and three groups of males castrated either postnatally (24-26 days of age), prepubertally (14.5 months of age), or in adulthood. All three groups of castrated male wallabies showed a very low incidence of male sexual behavior in adult life, comparable to that shown by the untreated females. Adult female wallabies with 100-mg testosterone implants showed a high incidence of male sexual behavior which was indistinguishable from that shown by intact males. The results suggest that sex differences in male-type behavior in the tammar wallaby are due to short-term inductive effects of testosterone acting on a sexually indifferent brain. There is no evidence of any long-term organizational effects of testosterone acting in fetal or neonatal life on the neural pathways controlling male-type sex behavior in this marsupial mammal.

Animals↗

PubMed1999

Estradiol accelerates extinction of a conditioned taste aversion in female and male rats.

Exogenous testosterone treatment prolongs extinction of conditioned taste aversions and estradiol treatment prevents testosterone from prolonging extinction in both gonadectomized males and females. Estradiol could require the presence of testosterone for its effect or its action alone could accelerate extinction. The first series of experiments were designed to test the hypothesis that estradiol accelerates extinction when it is given in the absence of testosterone. The results showed that estradiol accelerates extinction of conditioned taste aversions in the absence of testosterone in gonadectomized Sprague-Dawley females and Fischer 344 females and males. The second series of experiments were designed to determine whether estradiol and testosterone differ in the temporal requirements for their opposite effects on extinction. The results showed that estradiol can accelerate extinction when it is present before and during acquisition (from 8 days before until 3 days after acquisition) or when it is present before and during extinction (from 2 days after acquisition, which was 23 days before extinction, until extinction trials were terminated). This is in contrast to a previous finding that testosterone prolongs extinction only when it is present before and during extinction. The following two hypotheses were suggested to account for the temporal effects of estradiol on extinction of conditioned taste aversions: (1) the presence of estradiol during acquisition reduces the effectiveness of LiCl through its action on the opioid system, and the presence of estradiol during extinction activates a neural pathway, such as that associated with activity levels, that accelerates extinction of passive avoidance tasks in general or (2) the presence of estradiol before, not during, acquisition or extinction accelerates extinction because of its illness-inducing properties. Most of the evidence supports the second hypothesis.

Animals↗

PubMed2000

Leptin and metabolic control of reproduction.

Leptin treatment prevents the effects of fasting on reproductive processes in a variety of species. The mechanisms that underlie these effects have not been elucidated. Progress in this area of research might be facilitated by viewing reproductive processes in relation to mechanisms that maintain fuel homeostasis. Reproduction, food intake, and fuel partitioning can be viewed as homeostatic responses controlled by a sensory system that monitors metabolic signals. These signals are generated by changes in intracellular metabolic fuel availability and oxidation rather than by changes in the amount of body fat or by changes in any aspect of body composition. Leptin might be viewed as either a mediator or as a modulator of the intracellular metabolic signal. Consistent with its purported action as a mediator of the metabolic signal, leptin synthesis and secretion are influenced acutely by changes in metabolic fuel availability, and these changes might lead to changes in reproductive function. The effects of leptin treatment on reproduction are blocked by treatments that inhibit intracellular fuel oxidation. Metabolic signals that inhibit reproduction in leptin-treated animals might act via neural pathways that are independent of leptin's action. Alternatively, both leptin and metabolic inhibitors might interact at the level of intracellular fuel oxidation. In keeping with the possibility that leptin modulates the metabolic signal, leptin treatment increases fuel availability, uptake, and oxidation in particular tissues. Leptin might affect reproduction indirectly by altering fuel oxidation or other peripheral processes such as gastric emptying. Reproductive processes are among the most energetically expensive in the female repertoire. Because leptin increases energy expenditure while simultaneously inhibiting energy intake, it may have limited use as a long-term treatment for infertility.

Adipose Tissue↗

PubMed2001

Vasopressin and aggression in cross-fostered California mice (Peromyscus californicus) and white-footed mice (Peromyscus leucopus).

To examine how developmental experiences alter neural pathways associated with adult social behavior, we cross-fostered pups between the more aggressive and monogamous California mouse (Peromyscus californicus) and the less aggressive and polygamous white-footed mouse (P. leucopus). Cross-fostered males became more like their foster parents when tested as adults. Male white-footed mice became more aggressive only in an aggression test in a neutral arena, whereas the territorial California mice became less aggressive in resident-intruder aggression test, as measured by attack latency. Only the species that displayed a change in resident-intruder aggression showed a change in arginine vasopressin (AVP) levels: cross-fostered California mice had significantly lower levels of AVP-immunoreactive (AVP-ir) staining than controls in the bed nucleus of the stria terminalis (BNST) and the supraoptic nucleus (SON) and a nonsignificant trend toward lower levels in the medial amygdala (MA). Neither species showed changes in AVP-ir staining in a control area, the paraventricular nucleus (PVN). The changes in AVP-ir staining in the BNST and SON may not be caused by stress because cross-fostering was not associated with changes in adult plasma concentrations of two steroid hormones, corticosterone and testosterone, that have been associated with stress-related alterations in AVP pathways. These results suggest that manipulating the early parental environment can directly alter both a neurotransmitter system and species-typical patterns of social behavior, but that these effects may vary between species and under different social contexts.

Aggression↗