Supervisors info:
Αθανάσιος Πρωτόπαπας, Αναπληρωτής Καθηγητής, ΜΙΘΕ, ΕΚΠΑ
Ειρήνη Σκαλιόρα, Ερευνήτρια Γ', ΙΙΒΕΑΑ
Χριστίνα Δάλλα, Επίκουρη Καθηγήτρια, Ιατρική, ΕΚΠΑ
Summary:
Chronic stress can have a severe impact on the human body and brain, resulting in cognitive deficiencies and anxiety-related disorders like major depression. Animal research and neuroimaging techniques in humans have managed to identify mechanisms through which endogenous stress hormones influence the organism at the neuronal level, as well as specific brain areas. However, the intermediate level of the local brain networks has hardly been investigated.
In the present thesis we investigated the effect of chronic corticosterone administration on the spontaneous cortical network electrical activity of adolescent mice, while at the same time monitoring characteristic aspects of their anatomy, physiology and behaviour. C57/Bl6 male mice (n=24) received corticosterone in their water (50 μg/ml, diluted in 1% ethanol) for two weeks starting at postnatal day 28 (P28), while their body weight, food and liquid consumption were measured daily. A control group received regular water with ethanol for the same period. On day 13 of administration (P41), mice were examined on the Elevated Plus Maze in order to assess their behaviour and trace any anxiety traits. On the following days, mice were sacrificed, their brains extracted, cut in slices and put in a submerged chamber filled with oxygenated artificial cerebrospinal fluid.
Cortical network activity was recorded using the in vitro model of the spontaneously active brain slice. In this preparation, the isolated cortical network generates spontaneous periods of depolarization (Up states), interspersed with quiescent periods (Down states). This activity is exhibited in the absence of pharmacological or electrical stimulation, and is considered the default activity of the cortical circuits, reflecting endogenous connectivity. Spontaneous network activity was assessed by means of local field potential (LFP) recordings which were obtained from cortical layers II/III using low impedance (∼0.5 MΩ) glass pipettes filled with ACSF. Network activity events were analyzed and characterized as three different types of events (upstates, biphasics or multiphasics). Additionally, on the day of sacrifice the adrenal glands of mice were extracted and weighted. A subset of the initial group of treated mice, after receiving the corticosterone treatment for 2 weeks, were then left for 4 weeks with regular water to investigate if the corticosterone effects would disappear (n=8, washout group). After washout, they were also tested in the EPM, sacrificed in the following days and used in electrophysiology experiments.
We found that corticosterone administration had obvious (and anticipated) effects on the anatomy, physiology and behaviour of treated mice. CORT mice manifested a generally more anxious phenotype with reduced weight gain, while consuming equal amounts of food and significantly more liquid than the control group. Their adrenal glands were lighter than those of the control group, their tails were shorter and thinner and during the 2-week period of administration they produced more fecal boli and urine. In the Elevated Plus Maze, the CORT group covered significantly less distance and spent increased time in the closed arms compared to the control group. In spite of these clear signs of being under stress, the various parameters of Up state activity of the CORT group did not differ significantly from the control animals. During the washout period of the experiment, the CORT group recovered and all parameters returned to control levels. These results suggest that the endogenous cortical activity is a robust phenomenon under tight homeostatic regulation and is not significantly affected by corticosterone levels.
Keywords:
stress, corticosterone, electrophysiology, mice, brain, spontaneous, cortical, activity
