Research interests in the Zhdanova laboratory center around the role of endogenous factors secreted into the cerebrospinal fluid in regulating behavior and physiological functions. We are specifically interested in two secretory organs, the pineal gland and the subcommissural organ (SCO), both of which secrete into the third brain ventricle, as well as into the blood stream.

The pineal gland is a well-characterized secretory gland, the most well known product of which is melatonin. Melatonin is secreted in a precise circadian fashion and its circulating levels are high at night and low during the day in the majority of species studied. Our data show that in diurnal species, including humans, melatonin is involved in daily sleep regulation, promoting sleep and adjusting its circadian timing. We are now addressing the mechanisms of melatonin effects on sleep and cognitive performance by using two animal models, diurnal primates (rhesus monkeys) and diurnal fish (zebrafish). Such combination of phylogenetically distant animal models allows us to broaden the methodological approaches, ranging from continuous recordings of primate sleep and cognitive performance to gene analysis in a genetically well-characterized zebrafish.

Little is known about the physiological role of another circumventricular gland we are studying, the SCO. This is an interesting brain structure, which secretes large glycoproteins into the lumen of the third ventricle. Some of these secretory proteins can aggregate and, in many species, form a mysterious Reissner's fiber, spanning through the entire central canal of the spinal cord. We are focusing on the role the SCO might play in development, circadian rhythmicity and behavior.

Age-related decline in pineal and SCO activity or alterations induced by drugs of abuse may contribute to insomnia, cognitive alterations, reduced thresholds for anxiety or depression. We are addressing these issues by comparing secretory functions, sleep and behavior in old and young zebrafish and primates and in 'drug abusing' zebrafish.

Several collaborative projects add to the methodological approaches and the range of questions addressed by the laboratory:

1. Role of the circadian rhythms and melatonin in human age-related insomnia with Drs. Friedman and Yesavage; Stanford University.
2. Age-related changes in zebrafish behavior and circadian rhythms with Dr. Kishi; Dana Farber Cancer Institute, Harvard University.
3. Neuronal activity in behaving zebrafish with Dr. O'Malley; Northeastern University.
4. Pharmacokinetic analysis of melatonin in rhesus monkey CSF with Dr. Balis and McCully; NIH/NCI.

Signaling pathways involved in melatonin effects on sleep and cognition with Dr. Slack, Boston University School of Medicine, Department of Pathology.