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PubMed2000

Coitus-induced activation of c-fos and gonadotropin-releasing hormone in hypothalamic neurons in female rabbits.

Copulation induces hypothalamic release of neuropeptides and catecholamines, especially gonadotropin-releasing hormone (GnRH) and norepinephrine, in female rabbits. The forebrain distribution of GnRH cells and the cellular events responsible for the coitally induced GnRH surge have not been identified. We characterized the expression of c-fos mRNA before (0 min) and up to 60 min after coitus in forebrain tissues of mated and nonmated females and compared these findings with those in which single- and double-labeled GnRH/Fos protein cells were identified by immunocytochemistry (ICC). Enhanced expression of fos-mRNA occurred 30 min after coitus, especially in the anteroventral periventricular nucleus (AVPV), the encapsulated portion of the bed nucleus of the stria terminalis (BNSTe) and the ventrolateral hypothalamus (VLH); this increased fos-mRNA activity remained elevated at 60 min in the AVPV and VLH, and was reflected by Fos protein expression 90 min postcoitus. Both ICC Fos-labeled and ICC GnRH-labeled cells were widely distributed throughout the forebrain with postcoital increased double-labeling in the preoptic-septal areas, the anterior-medial hypothalamus and the VLH. The increased number of dual-labeled and unchanged number of single-labeled GnRH cells after coitus suggest some GnRH neurons were non-detected before coitus. Many dual-labeled neurons were adjacent to Fos-labeled cells, suggesting enhanced interneuronal input to GnRH cells after coitus. Collectively, the results suggest that coitus activates hypothalamic GnRH neurons via several loci that include the AVPV, BNSTe and VLH. The distinct anatomical location of the AVPV, BNSTe and VLH further suggests that coital signals may reach the hypothalamus via separate neural pathways that are likely developed within the brainstem.

Animals↗

PubMed1999

Analysis of NO synthase expression in neuronal, astroglial and fibroblast-like derivatives differentiating from PCC7-Mz1 embryonic carcinoma cells.

We studied the expression of the NO synthase isoforms in an in vitro model of neural development using RT-PCR, Western blot and immunohistochemistry. Murine PCC7-Mz1 cells (Jostock et al., Eur. J. Cell Biol. 76, 63-76, 1998) differentiate in the presence of all-trans retinoic acid and dibutyryl cAMP along the neural pathway into neuron-like, fibroblast-like and astroglia-like cells. Undifferentiated cells showed immunofluorescent staining for neuronal-type NOS I and endothelial-type NOS III. This expression pattern was retained in those cells differentiating into neurofilament- and tau protein-positive neuronal cells. Thymocyte alloantigen (Thy1.2/CD 90.2)-positive fibroblasts, appearing around day 3, and glial fibrillary acidic protein (GFAP)-positive astroglial cells, appearing after day 6 of differentiation, stained negative for any NOS isoform. Starting at day 6 of differentiation, expression of inducible-type NOS II could be stimulated with cytokines in a subset of cells, which may represent activated astrocytes. NOS II was always undetectable in non-induced cultures. These data indicate that the ability of stem cells to express NOS I and NOS III is only retained when the cells differentiate along the neuronal lineage, while a small subpopulation of cells acquires the ability to express NOS II in response to cytokines.

Animals↗

PubMed2004

Tickle.

Tickle is a familiar sensation that may have two components: a light or feather-type noxious sensation termed by Hall and Allin as knismesis, and a heavy or laughter-associated sensation termed gargalesis. Studies on the sensation of tickle have generally been on one sensation or the other, but not on both. In pleasurable, laughter-associated tickle there are elements of touch and pleasure, but the sensation may be a synthesis of touch and itch, with receptors, neural pathways or central receptors different from knismesis. It is unclear why some skin sites are more ticklish than other sites. Laughter-associated tickle might best be considered a social behavior rather than a reflex. This behavior provides interaction between mother and child, helps to integrate a child with peers and adults in play, and may become part of the mating ritual or sexual foreplay. In tickle play there are elements of dominance and submission, with accompanying laughter and withdrawal developed as the signals of submission. In this scenario, ticklish areas of skin might be considered those areas most vital to the ticklee and allowed to be invaded in the dominance submission play.

Humans↗

PubMed1980

Effects of halothane on the vestibulo-ocular reflex.

The differential effect of halothane on the characteristics of fast and slow components of vestibular nystagmus was investigated in rabbits. Eye movements were monitored using the "magnetic search coil" method and evaluated with the aid of a laboratory minicomputer. Low concentrations of halothane act preferentially on the fast component. There is a shift of the position threshold of fast component generation toward the periphery of the orbit and a diminution of the eye velocity during this nystagmus phase. Higher steady state concentrations of halothane reduced the velocity of the slow components whereby there is an increase in the amplitude of stimulation necessary to produce vestibulo-ocular responses of a magnitude to exceed the threshold of fast components. The results support the hypothesis that there are independent neural pathways for the production of fast and slow components of nystagmus whose neurons have different sensitivities to anesthetic agents.

Animals↗

PubMedDate not supplied

Pathophysiology and management of cupulolithiasis.

Substantial support for the concept that the posterior semicircular canal is responsible for benign paroxysmal positional vertigo comes from four sources: clinical observations, temporal bone histopathology, experimental observations, and results of selective denervation of the posterior canal crista (singular neurectomy). The complete immediate relief of the positional vertigo and nystagmus that resulted from 39 of 40 singular neurectomies establishes this procedure as an effective management for patients with the chronic disabling form of cupulolithiasis. The ocular response in cupulolithiasis and the release nystagmus that follows singular neurectomy are explained by neural pathways that have been previously elucidated by anatomic and physiologic techniques. Although sensorineural hearing loss followed surgery three times among the first 15 patients, hearing loss has not occurred in the last 25 operations for cupulolithiasis.

Adult↗

PubMedDate not supplied

Contractile properties of laryngeal muscles in young and old baboons.

Aging is associated with changes in voice and/or laryngeal protective reflexes in humans. To assess the role of the laryngeal muscles in this change, we have examined in vitro thyroarytenoid (vocalis) muscles excised from the larynxes of young and old baboons. Contractile properties, fatigue characteristics, and resting oxygen consumption of these muscles were measured. The results indicate that the thyroarytenoid muscle of the baboon is a fast muscle that is resistant to fatigue. The thyroarytenoid muscles of older baboons contracted more slowly and recovered less rapidly from fatigue induced by prolonged contractions but developed more maximum active tension than thyroarytenoid muscles of young adult baboons. These small differences in the characteristics of thyroarytenoid muscle of older baboons are probably not sufficient to explain observed changes in laryngeal function in the elderly. The results suggest that changes in neural pathways and/or morphology of the larynx may play a larger role in the altered laryngeal function with age.

Aging↗

PubMed2002

Allatostatins of the tiger prawn, Penaeus monodon (Crustacea: Penaeidea).

More than 40 peptides belonging to the -Y/FXFGL-NH(2) allatostatin superfamily have been isolated and identified from the central nervous system (CNS) of the tiger prawn, Penaeus monodon (Crustacea: Penaeidea). The peptides can be arranged in seven sub-groups according to the variable post-tyrosyl residue represented by Ala, Gly, Ser, Thr, Asn, Asp, and Glu. Two of the residues (Thr and Glu) have not been observed in this position previously in either insects or crustaceans. Also reported for the first time for allatostatins, two of the peptides are N-terminally blocked by a pyroglutamic acid residue. The yields of certain peptides with similar amino acid sequences to each other were, in some instances, very different. As an example, the yield of ANQYTFGL-NH(2) was 2pmol, compared with ASQYTFGL-NH(2), with a yield of 156 pmol. There are several possibilities to account for this. If, as in all species so far investigated, there is a single allatostatin gene in P. monodon, then it would appear that different sub-populations have contributed mutant forms of particular peptides to the extract. Another, less likely possibility is that this species has more than one allatostatin gene, producing a variable array of peptides albeit in different molar ratios. Several peptides were present apparently as a result of the loss of one or more residues at the N-terminus of a larger form, either due to N-terminal degradation or specific post-translational processing. The number of peptides identified exceeds that for any other insect or crustacean species previously investigated. None is identical to any of the 60-70 insect allatostatins so far identified, and only three are common to other crustaceans. Immunohistochemical study of the CNS of P. monodon, with the same antisera as used to monitor the purification, confirms the widespread nature and complexity of allatostatinergic neural pathways in arthropods. Thus, all neuromeres of the brain, and all except one of the ventral cord ganglia, possess allatostatin neurons and extensive areas of allatostatin-innervated neuropile. In addition to the cytological evidence that the allatostatins act as neurotransmitters, associated with tissues as varied as eyes and legs, their presence in neurohemal areas such as the sinus gland and the perineural sheath of the thoracic ganglia suggests a neuroendocrine function. As well as posing a challenge to physiologists assigning specific functions to the allatostatins, their extensive intra-species multiplicity, linked to their inter-species variability, also presents a complex problem to geneticists and evolutionists.

Amino Acid Sequence↗

PubMed1997

Use of antagonists to define tachykininergic control of intestinal motility in pigs.

The involvement of the tachykinins in extrinsic nervous control of motility was studied in isolated, vascularly perfused, porcine ileal segments. Substance P and neurokinin A (10(-8) M) stimulated motility, and nonpeptide NK1 and NK2 receptor antagonists (10(-6) M) abolished this. Electrical stimulation of the mixed extrinsic nerves (8 Hz) had no effect alone or with atropine (10(-6) M) or phentolamine (10(-5) M), but increased motility during coinfusion of both blockers. This effect was abolished by hexamethonium (3 x 10(-5) M), and was reduced by over 80% by the NK1 receptor antagonist. As previously shown, substance P and neurokinin A were released during nerve stimulation, only during blockade of alpha-adrenergic and muscarinic receptors, and the release was abolished by hexamethonium. Capsaicin infusions (10(-5) M) increased substance P and neurokinin A release, and weakly stimulated small intestinal motility, but this was not inhibited by the tachykinin antagonists. Our results suggest that intrinsic tachykinin-producing neurons, controlled by extrinsic, nicotinic, excitatory neural pathways, and extrinsic adrenergic, inhibitory pathways, participate in the regulation of small intestinal motility.

Animals↗

PubMed1984

Galactorrhea secondary to chest wall surgery in an adolescent.

Although nonpuerperal galactorrhea in youth may be a sign of pituitary prolactinoma, the etiology may be benign and extensive neurologic or endocrinologic evaluation and treatment may be unnecessary. An 18-year-old female with an unusual but benign form of transient galactorrhea due to chest wall surgery is reported. It is hypothesized that the sectioning of the intercostal nerves may result in reflex stimulation of hypothalamic centers controlling lactation through the same neural pathways involved in puerperal lactation. The patient experienced galactorrhea for two months and transient amenorrhea. She is asymptomatic without galactorrhea at nine months follow up.

Adolescent↗

PubMed2000

Psychotomimetics moderately affect dopamine receptor binding in the rat brain.

The hypothesis that psychotomimetics induce a rapid dopamine receptor regulation that could participate in the expression of the brain dopaminergic overactivation and in the early signs of psychotic-like behaviour, was checked by radioligand binding on rat brain cryosections. For this purpose, subchronic 7-day-d-amphetamine pretreatment was combined with acute amphetamine, phencyclidine or LSD challenge. Acute application of psychotomimetics affected only striatal and accumbens but not nigral and olfactory dopamine receptor binding after 40 min, while subchronic amphetamine expressed no effect, as revealed by two-way ANOVA. Post-hoc statistical analysis showed that only striatal and accumbens[3H]SCH 23390 binding decrease (10-12%) following phencyclidine and striatal [3H]spiperone binding increase (11%) after acute amphetamine were significant. It is assumed that such moderate dopamine receptor binding changes probably reflect the fast receptor regulation responses without important influence on a proposed drug-induced dopaminergic overactivity. The registered alterations of D1 receptor binding after phencyclidine are suggested to be capable to modify the activity of some other neural pathways in the basal ganglia and thus participate in a psychotic-like behaviour.

Amphetamine↗

PubMedDate not supplied

Somatic mosaic approaches and the aging brain.

Elucidating the function of neural pathways in the aging mammalian brain is a formidable task. Mechanisms that underlie aging and pathogenesis in specific brain circuits have been particularly elusive. However, animal models have been exploited in studies related to normative and pathogenic aging. Traditional transgenic animals represent permanent germ-line alterations in gene expression; changes that are present during development, remain indefinitely and likely invoke compensatory changes in the animal. In contrast, conditional transgenic animals combined with somatic gene delivery afford precise temporal and spatial gene regulation. In this review, we will detail current somatic mosaic approaches to study networks involved in the recognition, interpretation and recall of spatial representations, the septohippocampal pathway. We will also highlight potential uses for this approach in Alzheimer's disease, a complex pathophysiological state involving changes in many cellular pathways.

Aging↗

PubMed2003

Therapeutic approaches to prion diseases.

Prion diseases are unique in that they comprise sporadic, genetic, and iatrogenically or environmentally acquired forms. When disease is acquired by peripheral route, neuroinvasion occurs via at least two different neural pathways (vague and splanchnic nerves) and is usually preceded by prion propagation in secondary lymphoid organs. Conversely, in the other etiologic forms, PrPSc formation occurs within, and is apparently limited to, the CNS. Longitudinal studies on experimental scrapie indicate that substantial neuropathologic changes (i.e., glial activation and nerve cell degeneration) already are present before the onset of symptoms and are topographically related to PrPSc deposits. Accordingly, any effective intervention should start during the preclinical stage of disease, and be aimed at preventing neuroinvasion or PrPSc propagation in the CNS. Unfortunately, no tests are available currently to detect presymptomatic individuals, except for carriers of pathogenic mutations of the PRNP gene. Inhibition of PrPSc formation can be achieved through (1) abrogation of PrPC synthesis or prevention of its transport to the cell surface; (2) stabilization of the PrPC structure to make its conformational change unfavorable; (3) sequestration of PrPSc; (4) reversion of PrPSc to a protease-sensitive form; or (5) interference with the interaction between PrPC, PrPSc, and other macromolecules that feature in the conversion process. The compounds that have some effectiveness in in vitro, cell culture, or animal models of prion disease seem to operate through one of these mechanisms (see Table 1); however, even the most effective drugs only work when administered at the time of infection or very short thereafter, and these conditions are incurable at present. The heterogeneity and complexity of the etiopathogenesis of prion diseases suggest that various strategies and a combination of several compounds with different modes of actions are likely necessary for prevention and treatment. Major efforts should be focused on the development of preclinical diagnostic tests in conjunction with immunization strategies for diseases acquired by peripheral route and identification of more effective compounds for the other etiological forms.

Animals↗

PubMed1997

The sensitivity of biological tissue to ultrasound.

Mammalian tissues have differing sensitivities to damage by physical agents such as ultrasound. This article evaluates the scientific data in terms of known physical mechanisms of interaction and the impact on pre- and postnatal tissues. Actively dividing cells of the embryonic and fetal central nervous system are most readily disturbed. As a diagnostic ultrasound beam envelopes a small volume of tissue, it is possible that the effects of mild disturbance may not be detected unless major neural pathways are involved. There is evidence that ultrasound can be detected by the central nervous system; however, this does not necessarily imply that the bioeffect is hazardous to the fetus. Biologically significant temperature increases can occur at or near to bone in the fetus from the second trimester, if the beam is held stationary for more than 30 s in some pulsed Doppler applications. In this way, sensory organs that are encased in bone may be susceptible to heating by conduction. Reports in animals and humans of retarded growth and development following frequent exposures to diagnostic ultrasound, in the absence of significant heating, are difficult to explain from the current knowledge of ultrasound mechanisms. There is no evidence of cavitation effects occurring in the soft tissues of the fetus when exposed to diagnostic ultrasound; however, the possibility exists that such effects may be enhanced by the introduction of echo-contrast agents.

Animals↗

PubMed2000

Visualisation of AMPA binding sites in the brain of mice lacking the adenosine A(2a) receptor.

Adenosine A(2a) receptor knockout mice (A(2a)R k/o) have been characterised as hypertensive, aggressive, anxious and hypoalgesic [12]. Thus, the present study was designed to investigate markers of glutamatergic transmission in specific brain nuclei associated with autonomic regulation. Visualisation of alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid binding sites in the brains of A(2a)R k/o mice was achieved by utilising quantitative receptor autoradiography with (S)-[(3)H]-5-fluorowillardiine ([(3)H]FW:10 nM) on slide-mounted sections of mouse-brain. [(3)H]FW binding significantly increased in the nucleus tractus solitarius and area postrema of A(2a)R k/o mice compared with wildtype CD-1 mice. In other autonomic nuclei examined, binding was unchanged between wildtype and knockout mice. The present study suggests that glutamatergic neurotransmission within certain neural pathways involved in autonomic and motor control is altered in the brains of A(2a)R k/o mice.

Animals↗

PubMed1999

Pathological PrP is abundant in sympathetic and sensory ganglia of hamsters fed with scrapie.

Although the ultimate target of infection is the CNS, there is evidence that the peripheral nervous system (PNS) is involved in the pathogenesis of Transmissible Spongiform Encephalopathies (TSEs). We used immunocytochemistry to identify the presence of pathological accumulations of a host protein, PrP, in the CNS and PNS (sensory and autonomic ganglia) of hamsters orally infected with 263K scrapie. All hamsters showed pathological deposition of PrP in most brain areas, along the length of the spinal cord, in nodose (NG) and dorsal root (DRG) ganglia and in the coeliac mesenteric ganglion complex (CMGC). In one case, scant deposition was observed along a few axons of the vagus nerve. This finding suggests that, after oral challenge, TSE infectious agent uses neural pathways and ganglia of the peripheral nervous system to reach target sites in the CNS.

Administration, Oral↗

PubMed1999

Immunohistochemical localization of serotonin receptors in the rat suprachiasmatic nucleus.

Serotonin (5-HT) has been implicated in the regulation of circadian rhythms through its actions on the suprachiasmatic nucleus (SCN). Recent data suggests that, along with excitatory amino acids, serotonin may be important in the neural pathway that mediates the transmission of photic information to the circadian system. The present study uses immunohistochemistry to examine the presence of three different 5-HT receptor subtypes in the suprachiasmatic nucleus (5-HT2a, 5-HT2c and 5-HT7) in male albino Wistar rats. In the SCN, there was a considerable amount of 5-HT2c-receptor-like immunoreactivity, a lesser amount of 5-HT2a positive fibres and no staining with antiserum against the 5-HT7 receptor subtype. These results are compatible with previous pharmacological evidence obtained in our laboratory showing that serotonin acting through the 5-HT2c receptor subtype may be important in the phase shifting effects of light on the circadian system.

Animals↗

PubMed1999

Electrophysiological evidence for the role of substance P in retinohypothalamic transmission in the rat.

The retinohypothalamic tract (RHT) is a neural pathway through which photic time cues are delivered directly to the mammalian circadian pacemaker in the suprachiasmatic nucleus (SCN). Although the excitatory amino acid glutamate is the primary neurotransmitter in the RHT, other substances such as substance P (SPq also have been suggested to play a role. The present study tested the hypothesis that SP participates in retinohypothalamic transmission and selectively modulates either N-methyl-D-aspartate (NMDA) or non-NMDA receptor-mediated neurotransmission. The SP antagonist L-703,606 depressed the excitatory postsynaptic current (EPSC) evoked by optic nerve stimulation in SCN neurons in rat hypothalamic slices. The SP antagonist also had a similar depressive effect on the NMDA and non-NMDA receptor-mediated components of the EPSC. These results suggest that SP is an excitatory neuromodulator contributing to the expression of both the NMDA and non-NMDA receptor-mediated components of retinohypothalamic transmission.

2-Amino-5-phosphonovalerate↗

PubMed1999

Involvement of trigeminal subnucleus caudalis (medullary dorsal horn) in craniofacial nociceptive reflex activity.

We have previously shown that an increase in electromyographic (EMG) activity of digastric (DIG) and masseter (MASS) muscles can be reflexly evoked by injection into the rat's temporomandibular joint (TMJ) region of the small-fibre excitant and inflammatory irritant mustard oil (MO). Since the trigeminal (V) subnucleus caudalis (Vc, i.e. medullary dorsal horn) has traditionally been viewed as an essential brainstem relay site of nociceptive information from craniofacial tissues, an EMG study was carried out in 45 anaesthetized rats to determine if Vc is involved in the MO-evoked increases in jaw muscle EMG activity. The effects of histologically confirmed surgical or chemical lesions of Vc on this evoked EMG activity were tested in different groups of rats. MO injection into the left TMJ region of intact rats evoked bilateral increases in EMG activity of DIG and MASS which could be significantly reduced by surgical transection of the left caudal brainstem at the obex level; MO injection into the right TMJ region in these same rats still readily evoked increases in EMG activity. A sagittal section medial to Vc or transection at the level of the second cervical spinal segment did not produce any significant reduction in the reflexly evoked EMG activity. Neurones in Vc, as opposed to fibres of passage, appear to be important for the MO-evoked EMG activity, since injection into Vc of the neurotoxic chemical ibotenic acid significantly reduced the mustard oil-evoked EMG activity. The Vc also appears to play a role in the activation of contralateral V motoneurons, as evidenced by the activation of the contralateral DIG and MASS muscles by the injection of MO into the left TMJ region of intact rats and by the reduction of this evoked EMG activity in the contralateral DIG and MASS of rats with a surgical transection or ibotenic acid lesion of the left Vc. These findings suggest that Vc may be a critical element in the neural pathways underlying the reflex responses evoked bilaterally in DIG and MASS muscles by noxious stimulation of the TMJ region.

Animals↗