CC BY
39STH MULTIDISCIPLINARY INTERNATIONAL
Conference of Biological Psychiatry
«Stress and Behavior»
Proceedings of the 9th International Multidisciplinary Conference «Stress and behavior» Saint-Petersburg, Russia, 16-19 May 2005 Editor: Allan V. Kalueff, PhD
CONFERENCE ABSTRACTS
3. EPILEPSY
INHIBITOR OF HSP EXPRESSION QUERCETIN DOES NOT ALTER OPEN FIELD BEHAVIOR IN THE RAT PREDISPOSED TO AUDIOGENIC SEIZURES
M.V. Chernyshev, L.E. Nitsinskaya Sechenov Institute of Evolutionary Physiology and Biochemistry RAS, St. Petersburg, Russia
Heat shock proteins (HSPs) expression in the nervous system are related to a wide variety of stresses (basically thermal and oxidative). Exposing the mammalian CNS to nonlethal heat stress (thermal preconditioning) increases HSPs such as inducible HSP 70kDa and enhances the viability of neurons under various subsequent stresses (Amin et al., 1996; Kelty et al., 2002). There are numerous studies on molecular mechanisms of protective functions of HSP expression in nervous tissues, whereas behavioral experimental research in this area remains obscure. However, some experiments in animal models (Pizarro et al., 2003; Ambrosini et al., 2005) have shown a positive role of HSP 70 in learning and memory in stressed and non-stressed rats. Recently, a special attention was paid to an inhibitor of HSP 70 expression such as bioflavanoid quercetin, due to its influence on various biochemical processes. This flavonoid possesses pronounced antioxidative properties that finds a wide range of therapeutical perspectives. In animal models, quercetin was found to mitigate oxidative stress and cell damages induced by ischemia and ultraviolet irradiation (Brookes et al., 2002; Inal et al., 2002). It may reverse abnormal cell growth and inhibit prostate cancer, etc. On the other hand, quercetin markedly inhibits HSP expression under thermal and oxidative stress and thereby attenuates stress protective functions of organism, suggesting a negative side of its pharmacological application (Budagorova et al., 2003). Notably, epileptic seizures are accompanied by HSP 70 expression in the limbic system (Ferrer, 2002), suggesting possible biological effects of quercetin in animal models of epilepsy. The aim of the present study was to make a comparative analysis of possible behavioral changes following quercetin injections in rats predisposed to audiogenic seizures. Experiments were carried out on adult male rats Wistar of two groups. Group I — control rats (n = 15, 250 g). Group II — rats predisposed to audiogenic seizures (n = 7, 200 g). All animals were kept in a control environment maintained at a constant temperature (23 °C) with free access to food and water. In both groups, quercetin injections were performed i.p. Each animal at 2 different days (with a 3-day interval) was injected (5 mg/kg) with quercetin or saline (control). Each group was injected with both quecetin and saline at the same day. Animal behavior was tested for 10-min in the open field 4 h after the injections. We recorded the following parameters of behavior: the number and the duration of peripheral visits; the number and the duration of inner visits; total number of visits; the number and the duration of freezing (NF and DF), grooming; the number of vertical rears, and defecations. 3 days prior to injections, each group was tested for obtaining baseline data. Data were analyzed by Kruskal-Wallis and U-tests (P < 0.05). A comparison between the groups I and II showed significant differences in certain characteristics of behavior. The group II showed higher levels of total visits, inner visits, and vertical rears. These parameters indicate higher exploration in the group II (compared to the group I) also consistent with the marked decrease in the number of freezing. At the same time, the group II showed higher level of defecation indicating pronounced vegetative functions connected with emotionality. Overall, the group II differed from the group I in a higher level of exploratory and emotional activity. Quercetin injections in both groups did not alter any behavioral characteristics vs. controls. The lack of
ISSN 1606—8i8i
behavioral effects of Quercetin may be explained taking into account the specifics of stress factor in such an experiment. Inducible HSP 70 expression in nervous tissues is primarily associated with relatively severe stressors such as such as hyperthermia or hypoxia. In our experiments, placing an animal in the novel surroundings of the open field represented a relatively mild stressor. We suggest that quercetin injections may inhibit the enhancement of HSP 70 expression under open field stress, thus altering rat behavior. However, the strength of this stress appears to be mild to considerably increase the level of inducible HSP 70 in CNS. The study was supported by the RFRF grant 03-03-33034.
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