Wirkung der transkraniellen magnetisch applizierten intermittierenden Theta-Burst Stimulation auf die Entwicklung eines psychiatrischen Phänotyps im Rattenmodell maternaler Immunstimulation
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Beschreibung
Effects of Pre-Adolescent Transcranial Magnetic Stimulation on the Behavioural and Neuronal Phenotype of Rats of a Maternal Immune Stimulation Model
Schizophrenia is one of the most serious and most frequent psychiatric disorders in the world. Despite the use of modern antipsychotics in combination with individual psychotherapy, about 30 % of the patients relapse or show inadequate response to pharmacological treatment. Therefore, it is important to look for alternative treatment options. One promising method is transcranial magnetic stimulation, which can be applied in a non-invasive and painless fashion. A coil creates a magnetic field which, via the induced electric field within the brain, is able to depolarise or hyperpolarise neurons. It has an outlasting excitatory or inhibitory effect on brain activity when applied in a repetitive fashion. This way, magnetic stimulation may normalise unbalanced excitatory and inhibitory activity supposed to be one reason for psychiatric disorders. To create a schizophrenia-like phenotype in rats, we used the Poly(I:C) maternal immune stimulation model. Since brains are more plastic during development and thus more sensitive for disturbances but also corrective mechanisms, transcranial magnetic stimulation was applied before puberty at the age of 6 weeks. The intermittent theta-burst stimulation protocol (iTBS) had been chosen because it had the strongest modulatory effect on inhibitory cortical systems in previous studies. Behavioural abnormalities of patients who suffer from schizophrenia occur during adulthood; therefore, the rats were tested in different behaviour experiments at the age of 12 weeks. These included Elevated Plus Maze, Novel Object Recognition Test, Morris Water Maze, Pre-Pulse Inhibition Test, Sucrose Consumption Test and Porsolt Forced Swim Test. The rats’ brains were subsequently analysed by the aid of immunohistochemistry to determine the expression levels of the neuronal activity markers NeuN, Parvalbumin, Calbindin, cFos, Glutamate-Decarboxylase 67, and BDNF. Differences between NaCl Controls and Poly(I:C) animals as well as Verum and Sham iTBS treated animals were detected. iTBS-reated Poly(I:C) rats were less anxious than Poly(I:C) Sham rats in Elevated Plus Maze. In Novel Object Recognition Test Poly(I:C) Sham rats showed a deficit in long-term memory while they performed better than the other groups with regard to spatial learning and memory in Morris Water Maze on day 2 and 4. Porsolt Forced Swim Test revealed the NaCl Verum rats as being the most inactive group. No differences were found between groups in case of Pre-Pulse Inhibition. According to immunohistochemistry, iTBS significantly reduced the expression of Glutamate-Decarboxylase 67 and cFos in the prefrontal cortex. Both, in the nucleus accumbens and in the ventral tegmental area expression of Calbindin and Glutamate-Decarboxylase 67 significantly increased after iTBS in Poly(I:C) rats while cFos decreased in the ventral tegmental area. Effects within the dorsal and ventral hippocampus were highly variable. The results of this study show a long-lasting effect of iTBS and an improved learning ability after iTBS in Poly(I:C) rats and Controls. The absence of a Pre-Pulse Inhibition deficit in adult Poly(I:C) rats which had been treated with iTBS during adolescence could be one indication that this interventions has a positive effect, however, a couple of other factors like handling and testing the animals, their age and the time interval between stimulation and behavioural testing appear to modulate the behavioral and molecular phenotyp in addition.
Autor*in
Nadine Rittweger
Themen in »Wirkung der transkraniellen magnetisch applizierten intermittierenden Theta-Burst Stimulation auf die Entwicklung eines psychiatrischen Phänotyps im Rattenmodell maternaler Immunstimulation«
Immunhistochemie Ratten Schizophrenie Tiermodell Tierverhalten animal behaviour animal models immunohistochemistry rats schizophrenia transcranial magnetic stimulation (MeSH)