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V M Cassone

Publications and source records attributed to V M Cassone.

At least 37 records · Page 2Linked to original sources
PubMed1995

Comparative distribution of 2[125I]iodomelatonin binding in the brains of diurnal birds: outgroup analysis with turtles.

The roles that the pineal gland and its hormone melatonin play in the regulation of circadian rhythmicity and photoperiodism vary among vertebrate species. Recently, putative sites of melatonin action have been elucidated in several avian and mammalian species by application of in vitro binding of a radioiodinated melatonin agonist, 2[125I]iodomelatonin (IMEL) and autoradioradiography. These studies in mammals, birds and reptiles have indicated profound differences in the distribution of IMEL binding between these diverse groups, suggesting that these large differences in binding may reflect differences in melatonin function. The present study was performed to determine systematically whether the variance in IMEL binding among avian species corresponds to changes in circadian organization and/or phylogenetic relationships. The distribution of specific IMEL binding was determined in the brains from birds belonging to 14 different species in 5 Orders (Psittaciformes, Passeriformes, Columbiformes, Galliformes and Anseriformes) using in vitro binding, autoradiography and computer-assisted image analysis. The distribution was compared to a similar study in 3 species of turtles as an outgroup. The data indicated IMEL binding in retinorecipient structures of the circadian, tectofugal, thalamofugal and accessory optic visual pathways in all avian species. Relay nuclei and integrative structures of the tectofugal, thalamofugal, accessory optic, and limbic systems, however, bound the hormone to varying degrees. In turtles, binding was observed in retinorecipient structures of the thalamofugal visual pathway and in retinorecipient and integrative areas of the tectofugal visual pathway. No binding was observed in the pineal gland, tuberal hypothalamus or adenohypophysis in any avian or testudine species. This distribution is drastically different from that observed in mammals, where binding predominates in the pars tuberalis of the adenohypophysis and in the suprachiasmatic nucleus, suggesting that the circadian system may influence a wide array of sensory and integrative functions in birds and reptiles through the circadian secretion of melatonin, but that this capacity has been lost in mammals.

Animals↗
PubMed1995

The pineal gland: photoreception and coupling of behavioral, metabolic, and cardiovascular circadian outputs.

Although removal of the pineal gland has been shown to have very little effect on the mammalian circadian system in constant darkness (DD), several recent reports have suggested that the mammalian pineal gland may be more important for circadian organization in nocturnal rodents than was previously believed. Removal of the pineal gland (PINX) facilitates the disruptive effects of constant bright light on wheel-running rhythmicity. This suggests at least two possibilities for the role of the pineal gland in the mammalian circadian system. First, pinealectomized rats may perceive ambient light intensity to be brighter than do sham-operated (SHAM) rats. Second, the pineal gland, probably via its secretion of melatonin, may also be involved in coupling components of the circadian system. Coupling, as we see it, may occur at several levels of organization: (1) between retinohypothalamic afferents and suprachiasmatic nuclei (SCN) oscillatory neurons, (2) among multiple SCN oscillators, (3) between the SCN and their multiple outputs, and/or (4) among the multiple circadian outputs themselves. In this study we show that PINX rats free-run with a longer period in four different light intensities than do SHAM rats. Moreover, the rate of increase of tau is greater among PINX rats than among SHAM rats. This supports the first hypothesis. We also show that in PINX rats the circadian rhythms of wheel running, general activity, body temperature, and heart rate are all more disrupted in constant bright light than are those of SHAM rats, and each rhythmic output is disrupted in parallel. This supports the second hypothesis. Melatonin is probably not involved in coupling presynaptic elements of SCN afferents in the retinohypothalamic tract to pacemaking cells within the SCN, since enucleation has no effect on SCN 2-[125I]iodomelatonin (IMEL) binding. Together the data do not discount either of the two hypotheses but do restrict the possible levels at which the pineal gland is involved in coupling. These data also further support a growing body of literature indicating that the pineal gland and its hormone melatonin play a role in mammalian circadian organization.

Animals↗
PubMed1994

Retinohypothalamic projections and immunocytochemical analysis of the suprachiasmatic region of the desert iguana Dipsosaurus dorsalis.

Two separate and distinct retinal projections to the hypothalamus in the iguanid lizard Dipsosaurus dorsalis were described using horseradish peroxidase and cobalt-filling techniques. Both of the projections were unilateral and completely crossed; one terminated in the supraoptic nucleus and the other in the suprachiasmatic nucleus. Immunocytochemical analysis showed that the supraoptic nucleus contained cell bodies and fibers that cross-react with antibodies raised against arginine vasopressin, while the suprachiasmatic nucleus contained arginine vasopressin-like immunoreactive fibers emanating from cells in the nearby paraventricular nucleus. The suprachiasmatic nucleus contained a dense plexus of fibers that cross-reacted with neuropeptide-Y antibody. Antiserum against vasoactive intestinal polypeptide showed no reactivity in any part of the forebrain, while antiserum against serotonin showed sparse and uniform reactivity throughout the forebrain, including the suprachiasmatic nucleus. These results, together with other data, indicate that the suprachiasmatic nucleus of D. dorsalis is homologous to the suprachiasmatic nuclei of rodents, structures known to contain circadian pacemakers. We suggest that the suprachiasmatic nucleus may play a similar role in the circadian system of D. dorsalis.

Afferent Pathways↗
PubMed1994

The suprachiasmatic nucleus controls the circadian rhythm of heart rate via the sympathetic nervous system.

The mammalian suprachiasmatic nucleus (SCN) controls a wide variety of circadian behavioral and physiological processes. The specific motor output pathway(s) by which these diverse processes are controlled are unknown. The only established motor output of this system is the regulation of pineal melatonin synthesis via the sympathetic nervous system. It is therefore possible that other peripheral circadian rhythms are regulated similarly. To address this issue, body temperature (BT), general activity (GA), wheel-running activity (WR), and heart rate (HR) were recorded in laboratory rats, and the effects of SCN lesion (SCNX) and of pharmacological sympathectomy with guanethidine (GUAN) on these multiple circadian rhythms were determined. The SCNX abolished circadian patterns in all motor outputs, whereas sham animals showed robust rhythms in all measures. In contrast, guanethidine, which depleted peripheral but not central catecholamine content, selectively reduced HR circadian rhythmicity. Other rhythms (BT, GA, and WR) were unaffected. These results suggest that the SCN influences some peripheral targets via circadian regulation of the sympathetic nervous system, and other circadian outputs are regulated via different, unknown pathways.

Animals↗
PubMed1993

Pinealectomized rats entrain and phase-shift to melatonin injections in a dose-dependent manner.

Previous work has shown that daily injections of the pineal hormone melatonin (N-acetyl, 5-methoxytryptamine) entrain the free-running locomotor rhythms of rats held in constant darkness (with a median effective dose [ED50] of 5.45 +/- 1.33 micrograms/kg) and in constant bright light. The present experiments determined the dose-response characteristics of entrainment and phase shifting to daily and single melatonin injections in both sham-operated (SHAM) and pinealectomized (PINX) rats. The data indicated an ED50 of 332 +/- 53 ng/kg and 121 +/- 22 ng/kg for SHAM and PINX rats, respectively, during the entrainment experiment. The ED50's for the entrainment experiment were considerably lower than doses previously employed, and much lower than doses employed in reproductive and metabolic studies in rats and hamsters. The data indicated that no partial entrainment occurred; nor were there differences in phase angle, length of activity, or period among all effective doses. Next, a single injection of 1 mg/kg melatonin has previously been shown to cause a phase advance of approximately 45 min when administered at about circadian time (CT) 10. We found that both SHAM and PINX animals phase-advanced, in a dose-dependent manner to a single melatonin injection given at CT 10. The data for the phase-shifting experiment indicated an ED50 of 8.19 +/- 0.572 micrograms/kg and 2.16 +/- 0.326 micrograms/kg for SHAM and PINX animals, respectively, with an average phase advance of 40 min for both groups. Together, the data suggest that the presence of the pineal gland is not necessary for the effects of melatonin on the rat circadian system, and that PINX animals are marginally more sensitive to melatonin than their SHAM controls.

Adaptation, Physiological↗
PubMed1993

Melatonin, the pineal gland, and circadian rhythms.

Amniote circadian organization derives from the interactions of circadian oscillators and photoreceptors located in the hypothalamic suprachiasmatic nuclei (SCN), the pineal gland, and the eyes. In mammals, circadian organization is dominated by the SCN, which serve as "master pacemakers" in the control of a wide array of behavioral and physiological rhythms (including locomotion, sleep-wake, thermoregulation, cardiovascular function, and many endocrine processes). Among the rhythms under SCN control in mammals are the circadian synthesis and secretion of the pineal hormone melatonin, which relies on a multisynaptic pathway via the sympathetic nervous system to maintain and entrain rhythmicity in this hormone. Several studies have indicated that pineal melatonin feeds back on SCN rhythmicity to modulate circadian patterns of activity and other processes. However, the nature and system-level significance of this feedback are unknown. Recently published work indicates that although pinealectomy does not affect rat circadian rhythms in light-dark cycles or constant darkness, wheel-running activity rhythms are severely disrupted in constant light. These data suggest that either (1) pineal feedback regulates the light sensitivity of the SCN, and/or (2) it affects coupling among circadian oscillators within the SCN or between the SCN and its output. Research in our laboratory is currently addressing each of these hypotheses.

Animals↗
PubMed1992

The pineal gland influences rat circadian activity rhythms in constant light.

Mammalian circadian organization is believed to derive primarily from circadian oscillators within the hypothalamic suprachiasmatic nuclei (SCN). The SCN drives circadian rhythms of a wide array of functions (e.g., locomotion, body temperature, and several endocrine processes, including the circadian secretion of the pineal hormone melatonin). In contrast to the situation in several species of reptiles and birds, there is an extensive literature reporting little or no effect of pinealectomy on mammalian circadian rhythms. However, recent research has indicated that the SCN and circadian systems of several mammalian species are highly sensitive to exogenous melatonin, raising the possibility that endogenous pineal hormone may provide feedback in the control of overt circadian rhythms. To determine the role of the pineal gland in rat circadian rhythms, the effects of pinealectomy on locomotor rhythms in constant light (LL) and constant darkness (DD) were studied. The results indicated that the circadian rhythms of pinealectomized rats but not sham-operated controls dissociated into multiple ultradian components in LL and recoupled into circadian patterns only after 12-21 days in DD. The data suggest that pineal feedback may modulate sensitivity to light and/or provide coupling among multiple circadian oscillators within the SCN.

Activity Cycles↗
PubMed1992

Daily and circadian regulation of 2-[125I]iodomelatonin binding in the chick brain.

The pineal gland and its hormone melatonin are important in the control of circadian rhythms in birds. Recent research has indicated the presence of high affinity melatonin-binding sites in a wide array of avian cerebral structures. In this study melatonin-binding sites were localized and characterized in the brains of 2-week-old chicks using in vitro autoradiography and image analysis of 2-[125I]iodomelatonin (IMEL) binding. The IMEL binding predominated in the major components of the chick's visual and auditory systems. These brain binding sites showed a daily variation in IMEL binding, with a higher density of binding during the daytime. A significant peak in IMEL binding was observed in the late afternoon, Zeitgeber time 10. This rhythm of IMEL binding continued in constant darkness, with the peak at circadian time 10. The amplitude of the peak was increased in constant darkness in all structures, with the exception of the ectostriatum and neostriatum. Scatchard analysis of the binding revealed an average increase of 45 +/- 5% in the number of binding sites in the daytime vs. nighttime samples, with little change in the binding affinities, indicating that the rhythm in binding is caused by an increase in the total number of binding sites available in the daytime tissue, rather than an increase in the affinity of the binding sites. The data suggest that a rhythm of melatonin sensitivity in a diverse set of cerebral structures may regulate a temporal control of their function.

Animals↗
PubMed1990

Hypothalamic regulation of circadian noradrenergic input to the chick pineal gland.

While the avian pineal gland contains circadian oscillators and photoreceptors capable of producing circadian rhythms of the hormone melatonin, it is extensively innervated by post-ganglionic fibers of the superior cervical ganglia which release norepinephrine (NE) rhythmically. Norepinephrine turnover is higher during subjective day than during subjective night. In mammals, this rhythmic input, which is higher in subjective night than subjective day, derives from the hypothalamic suprachiasmatic nuclei (SCN) and is essential for rhythmic melatonin production. The present study was designed to determine whether one of two candidates for the avian homologue of the mammalian SCN is necessary for rhythmic NE turnover in the chick pineal gland. Either electrolytic lesions or sham lesions were delivered to the periventricular preoptic nuclei (PPN) or to the visual suprachiasmatic nucleus (vSCN). After recovery, the rates of decline in [NE] were determined following pretreatment with alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, at mid-subjective day or at mid-subjective night. Birds receiving sham surgeries in either PPN or vSCN and birds receiving lesions of the PPN exhibited rhythmicity in NE turnover. No rhythm of NE turnover could be determined in birds with ablated vSCN.

Animals↗
PubMed1990

Effects of melatonin on vertebrate circadian systems.

In many species of vertebrates the pineal gland and its indoleamine hormone melatonin play central roles in the control of circadian rhythms, whereas in some species, the pineal gland appears to hold little importance. However, recent research indicates that the circadian rhythms of many species of reptiles, birds and mammals, including humans, are synchronized by the administration of exogenous melatonin. These studies have led to questions concerning the role of this hormone in circadian organization in general. Studies of the sites and mechanisms of melatonin action further indicate that melatonin may be an excellent pharmacological tool for research on the cellular mechanisms of circadian clock function and have pointed to the possibility that melatonin or melatonin analogues may be therapeutically useful for the control of circadian clock dysfunctions such as jet lag, shift-work syndrome and sleep disorders.

Animals↗
PubMed1989

Effects of melatonin on neuronal activity in the rat suprachiasmatic nucleus in vitro.

The pineal hormone melatonin is believed to act directly on the hypothalamic suprachiasmatic nuclei (SCN), which are principal circadian pacemakers in rodents, although direct demonstration of this is lacking. To determine whether the SCN are sensitive to melatonin electrophysiologically, we investigated the effect of melatonin on rat SCN single-unit activity in an in vitro hypothalamic slice preparation. SCN single-unit activity was inhibited by melatonin superfusion during the late subjective day in a dose-dependent manner but not at other times of day, supporting the view that melatonin acts directly on SCN neurons.

Action Potentials↗
PubMed1989

Paraventricular nucleus projections mediating pineal melatonin and gonadal responses to photoperiod in the hamster.

Knife cuts were placed around the paraventricular nucleus of the hypothalamus (PVN) in order to identify the pathways mediating photoperiodism and pineal melatonin production in male golden hamsters. Cuts in the coronal plane caudal to the PVN, have no effect on photoperiodic control of the testes unless they actually damage the PVN. Bilateral parasagittal cuts at the medial border of the lateral hypothalamus block short photoperiod-induced gonadal regression. Nighttime levels of pineal melatonin are reduced by these cuts, but unaffected by caudal cuts. Projections from the lateral PVN region descending towards the spinal cord appear to be critical for the control of pineal melatonin production and the control of the testicular function by short photoperiod.

Animals↗
PubMed1989

Melatonin receptors in chick brain: characterization and localization.

Melatonin receptors in chick brain were characterized by RRA and localized by in vitro autoradiography, using [125I]melatonin [( 125I]MEL), a biologically active melatonin analog. In membranes from whole brain, radioreceptor studies revealed a high affinity [125I]MEL binding site with an equilibrium dissociation constant of 47.2 +/- 11.5 (mean +/- SEM) pM and a density of 37.8 +/- 8.5 fmol/mg protein. Binding was reversible and competitively inhibited by melatonin and closely related melatonin analogs, but not be norepinephrine or serotonin. In vitro autoradiographic studies of brain revealed a widespread distribution of melatonin receptors. Specific I-MEL binding was observed in retinorecipient and integrative nuclei of the visual system including the avian homolog of the mammalian suprachiasmatic nuclei. Auditory relay nuclei and limbic structures associated with arousal and vocalization were also specifically labeled. This widespread distribution of putative melatonin receptors in chick brain is in marked contrast to the very restricted distribution of melatonin receptors in mammalian brain and suggests that avian sensory systems are affected by melatonin.

Animals↗
PubMed1988

Circadian variation of [14C]2-deoxyglucose uptake within the suprachiasmatic nucleus of the house sparrow, Passer domesticus.

To determine whether the suprachiasmatic nuclei (SCN) of the house sparrow exhibit circadian variations in activity, metabolism within these and several other diencephalic structures was studied using the 2-deoxyglucose (2-DG) method at several times of day. Uptake of 2-DG was high at midday and mid-subjective day, but low at midnight within the SCN. Uptake was high at midday and low at midnight and mid-subjective day within the ventral lateral geniculate nucleus and lateral anterior nucleus, while no daily or circadian variation was observed within the periventricular preoptic nucleus. These data indicate that the avian SCN, as in mammals, express circadian rhythmicity.

Animals↗
PubMed1988

Effects of melatonin on 2-deoxy-[1-14C]glucose uptake within rat suprachiasmatic nucleus.

Previously, we have demonstrated that metabolic activity, shown by autoradiographic determination of 2-deoxy-[1-14C]glucose (2-DG) uptake, within the rat hypothalamic suprachiasmatic nuclei (SCN) was inhibited by subcutaneous injection of 1 mg/kg melatonin. To determine whether this effect was specific to a particular time of day, the effects of melatonin on 2-DG uptake were studied in several hypothalamic areas, including the SCN, supraoptic nuclei (SON), lateral hypothalamic area (LHA), and anterior hypothalamic area (AHA) every 4 h throughout the circadian day. In a second experiment, the effects of different melatonin doses were studied at the time of day at which melatonin had its maximal effect to determine the dose-response relationship of melatonin-induced inhibition of SCN 2-DG uptake. The data indicate that melatonin inhibited 2-DG uptake in the SCN alone at one time of day, primarily at circadian time (CT) 6 and CT10, 2-6 h before subjective dusk, and secondarily at CT22, just before subjective dawn. This effect was dose dependent with a 50% effective dose of 1.49 +/- 2.30 micrograms/kg. The temporal and dose-response characteristics of these effects are similar to those characterizing the entraining effects of melatonin on circadian patterns of locomotion and drinking.

Animals↗
PubMed1988

Comparative anatomy of the mammalian hypothalamic suprachiasmatic nucleus.

A detailed analysis of the cytoarchitecture, retinohypothalamic tract (RHT) projections, and immunohistochemical localization of major cell and fiber types within the hypothalamic suprachiasmatic nuclei (SCN) was conducted in five mammalian species: two species of opossum, the domestic cat, the guinea pig, and the house mouse. Cytoarchitectural and immunohistochemical studies were conducted in three additional species of marsupial mammals and in the domestic pig. The SCN in this diverse transect of mammalian taxonomy bear striking similarities. First, the SCN are similar in location, lying close to the third ventricle (3V) dorsal to the optic chiasm (OC), with a cytoarchitecture characterized by small, tightly packed neurons. Second, in all groups studied, the SCN receive bilateral retinal input. Third, the SCN contain immunohistochemically similar elements. These similarities suggest that the SCN developed characteristic features early in mammalian phylogeny. Some details of SCN organization vary among the species studied. In marsupials, vasopressin-like immunoreactive (VP-LI) and vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) cells codistribute primarily in the dorsomedial aspects of the SCN, while in eutherians, VP-LI and VIP-LI cells are separated into SCN subnuclei. Furthermore, the marsupial RHT projects to the periventricular dorsomedial region, whereas the eutherian RHT projects more ventrally in the SCN into the zone that typically contains VIP-LI perikarya.

Animals↗
PubMed1987

Retinohypothalamic projection and suprachiasmatic nucleus of the house sparrow, Passer domesticus.

The distribution of retinohypothalamic projections and the organization of the suprachiasmatic region of the hypothalamus was investigated in the house sparrow (Passer domesticus). Retinohypothalamic projections (RHT) were studied by two anterograde tracing methods, and hypothalamic organization was investigated immunohistochemically with antisera against a number of substances known to be present in the mammalian suprachiasmatic nucleus (SCN): bombesin (BBS), glutamic acid decarboxylase (GAD), 5-hydroxytryptamine (5HT), neuropeptide Y (NPY), neurotensin (NT), somatostatin (SS), substance P (SP), vasoactive intestinal polypeptide (VIP), and arginine vasopressin (AVP). Observations from these experiments were analysed within the framework of a cytoarchitectural study using Nissl-stained material. From this study, we have identified an area in the anterior hypothalamus which we believe is an avian homologue of the mammalian SCN. This area contains a nucleus located in close apposition to the optic chiasm between the dorsal supraoptic decussation (DSD) and the ventral lateral geniculate body (GLv) for much of its rostrocaudal extent. The central portion of this nucleus contains neurons that exhibit GAD- and BBS-like immunoreactivity and is the terminal field for the RHT. For this reason, we term this nucleus the visual SCN. It also contains axon plexuses exhibiting 5HT-like, SP-like, and NPY-like immunoreactivity and is bordered ventrally by AVP-like, SP-like, and NT-like immunoreactive cells and medially by VIP-like and SS-like immunoreactive cells. Although it is not established that these cell groups together compose a single suprachiasmatic nucleus, the organization in the avian brain of a nuclear complex with a retinorecipient area surrounded by nonvisual components would be very similar to that of the mammalian SCN.

Animals↗