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Biomedical subjects

Irina V Zhdanova

Publications and source records attributed to Irina V Zhdanova.

8 recordsLinked to original sources
PubMed2006

Cognitive aging in zebrafish.

BACKGROUND: Age-related impairments in cognitive functions represent a growing clinical and social issue. Genetic and behavioral characterization of animal models can provide critical information on the intrinsic and environmental factors that determine the deterioration or preservation of cognitive abilities throughout life. METHODOLOGY/PRINCIPAL FINDINGS: Behavior of wild-type, mutant and gamma-irradiated zebrafish (Danio rerio) was documented using image-analysis technique. Conditioned responses to spatial, visual and temporal cues were investigated in young, middle-aged and old animals. The results demonstrate that zebrafish aging is associated with changes in cognitive responses to emotionally positive and negative experiences, reduced generalization of adaptive associations, increased stereotypic and reduced exploratory behavior and altered temporal entrainment. Genetic upregulation of cholinergic transmission attenuates cognitive decline in middle-aged achesb55/+ mutants, compared to wild-type siblings. In contrast, the genotoxic stress of gamma-irradiation accelerates the onset of cognitive impairment in young zebrafish. CONCLUSIONS/SIGNIFICANCE: These findings would allow the use of powerful molecular biological resources accumulated in the zebrafish field to address the mechanisms of cognitive senescence, and promote the search for therapeutic strategies which may attenuate age-related cognitive decline.

Acetylcholinesterase↗
PubMed2005

Stimulation of melatonin receptors decreases calcium levels in xenopus tectal cells by activating GABA(C) receptors.

To investigate the physiological effects of melatonin receptors in the Xenopus tectum, we have used the fluorescent indicator Fluo-4 AM to monitor calcium dynamics of cells in tectal slices. Bath application of KCl elicited fluorescence increases that were reduced by melatonin. This effect was stronger at the end of the light period than at the end of the dark period. Melatonin increased gamma-aminobutyric acid-C (GABA(C))-receptor activity, as demonstrated by the ability of the GABA(C)-receptor antagonists, picrotoxin and TPMPA, to abolish the effects of melatonin. In contrast, neither the GABA(A)-receptor antagonist bicuculline nor the GABA(B)-receptor antagonist CGP 35348 diminished the effects of melatonin. RT-PCR analyses revealed expression of the 3 known melatonin receptors, MT1 (Mel1(a)), MT2 (Mel1(b)), and Mel1(c). Because the effect of melatonin on tectal calcium increases was antagonized by an MT2-selective antagonist, 4-P-PDOT, we performed Western blot analyses with an antibody to the MT2 receptor; the data indicate that the MT2 receptor is expressed primarily as a dimeric complex and is glycosylated. The receptor is present in higher amounts at the end of the light period than at the end of the dark period, in a pattern complementary to the changes in melatonin levels, which are higher during the night than during the day. These results imply that melatonin, acting by MT2 receptors, modulates GABA(C) receptor activity in the optic tectum and that this effect is influenced by the light-dark cycle.

Aniline Compounds↗
PubMed2005

Melatonin as a hypnotic: pro.

In diurnal species, nocturnal melatonin secretion coincides with the habitual hours of sleep, in contrast to nocturnal animals which are at the peak of their activity while producing melatonin. Studies in humans, diurnal non-human primates, birds and fish show that melatonin treatment can facilitate sleep initiation during the daytime or improve altered overnight sleep. Behaviorally, the sleep-promoting effects of melatonin are distinctly different from those of common hypnotics and are not associated with alterations in sleep architecture. The effects of melatonin on sleep are mediated via specific melatonin receptors and physiologic doses of the hormone, those inducing circulating levels under 200 pg/ml, are sufficient to promote sleep in diurnal species. Aging reduces responsiveness to melatonin treatment and this correlates with reduced functional potency of melatonin receptors. Since melatonin receptors are present in different tissues and organs and involved in multiple physiologic functions, using physiologically relevant doses (0.1-0.3 mg, orally) and time of administration (at bedtime) is recommended, in order to avoid known and unknown side effects of melatonin treatment.

Adult↗
PubMed2004

Melatonin stimulates cell proliferation in zebrafish embryo and accelerates its development.

All vertebrates show a dramatic circadian rhythm in circulating melatonin with high levels at night and very low levels during daytime. In adults, melatonin is thought to synchronize other circadian rhythms and regulate seasonal rhythms in photoperiodic animals by acting on specific G-protein coupled receptors. The role of melatonin in development is unknown, even though melatonin receptors appear to be more highly expressed in developing embryos and neonates than in adults. In this study on zebrafish embryos, we describe a role for melatonin in increasing cell proliferation and accelerating development. We propose that melatonin has a role in extending the safe limit of proliferation rate at night to allow more rapid development when potentially damaging ultraviolet light is absent.

Animals↗
PubMed2004

Advances in the management of insomnia.

Insomnia is a prevalent disorder, altering night time sleep, daytime mood and performance. Current treatment strategies, used separately or in combination, include pharmacological, circadian, behavioural and cognitive therapy. An increased diversity of available hypnotics with different potency, pharmacodynamic and pharmacokinetic profiles and improved side effect profiles provides more flexibility in designing individual treatment strategies. Melatonin, a pineal hormone with acute sleep-promoting and chronobiotic properties, allows additional possibilities in treating insomnia and circadian sleep disorders. Current studies of processes involved in normal sleep regulation and pathophysiology of insomnia should result in the development of new medications based on physiological mechanisms of sleep.

Behavioral Medicine↗
PubMed2002

Melatonin alters behavior and cAMP levels in nucleus accumbens induced by cocaine treatment.

This study describes the effects of melatonin on cocaine-induced anxiety-like behavior and nucleus accumbens (NAc) cAMP levels in rats. Animals drinking a solution of melatonin (200 ng/ml) at night, either during repeated cocaine administration (15 mg/kg i.p., twice a day for 9 days) or during its withdrawal, showed less anxiety-like behavior in a defensive withdrawal paradigm 48 h after the last injection of cocaine. Melatonin did not alter behavior in control rats treated with saline. Animals exposed for 1 week to unrestricted free-choice oral melatonin self-administration (200 ng/ml) did not show preference for the drinking solution containing melatonin. Pretreatment with melatonin (200 ng/kg i.p. or 200 ng/ml orally) significantly attenuated the augmentation of cAMP levels in NAc following acute cocaine administration (15 mg/kg i.p.). Taken together, these results suggest that a low-dose night-time melatonin treatment results in anxiolytic-like effects in rats withdrawn from repeated cocaine administration, can antagonize cocaine-induced activation of NAc cAMP levels and has low dependence liability.

Animals↗
PubMed2002

Melatonin promotes sleep in three species of diurnal nonhuman primates.

Nocturnal melatonin secretion is concurrent with consolidated sleep episodes in diurnal mammals and physiological melatonin levels can promote sleep onset in humans and in pigtail macaques. In order to further investigate the effects of melatonin treatment on sleep parameters in diurnal nonhuman primates, three macaque species have been studied: Macaca nemestrina, Macaca fascicularis, and Macaca mulatta. Sleep was assessed using continuous actigraphic recording of motor activity in animals maintained under 12:12-h light/dark cycle. Oral doses of melatonin (5-320 microg/kg) were administered 2 h before lights-off time, with 5- and 10-microg/kg doses resulting in physiological circulating melatonin levels (31-95 pg/ml). The effects of melatonin administration were similar in three species studied and included significantly earlier sleep onset time and longer sleep period time, with no difference in time of awakening, following administration of both physiological (5-10 microg/kg) and pharmacological (20-320 microg/kg) doses. While low melatonin doses (5-20 microg/kg) did not significantly affect nighttime sleep efficiency, higher pharmacological doses reduced sleep efficiency and increased sleep fragmentation at night, and reduced spontaneous daytime locomotor activity. Daily administration of a 5-microg/kg dose for 4 weeks or gradually escalating melatonin doses (5-320 microg/kg over a 3-week period) did not result in the development of tolerance or sensitization to the effect of melatonin on sleep initiation or sleep period. These data affirm that sleep-promoting effects of melatonin observed in humans are also typical for diurnal primates. They also suggest that physiological and pharmacological melatonin levels might produce different effects on sleep efficiency and that nonhuman primates can serve as adequate animal model for studying the mechanisms of melatonin's action on sleep and performance.

Animals↗