Browsing by Subject "fluoxetine"

Obesity is a significant problem for public health. Obesity develops when systems controlling food intake and consumption are imbalanced. Many different brain areas and transmitters contribute to maintain energy balance. Signals that are secreted proportional to body's fat storage (leptin and insulin) regulate energy balance in a long run. Hormones that are secreted from gastrointestinal tract control food intake in a short run. These hormones are for example cholecystokinin, peptide YY and ghrelin. Drug treatment for obesity is limited because effective drugs are lacking. The only drug to treat obesity in Europe is orlistat but it's effectiveness is modest. The development for new antiobesity drugs has been busy. Problems in drug development have however delayed drugs in the market. The aim of this study was to develop a method with which we could measure how much food zebrafish (Danio rerio) has been eaten and to study how different drugs affect feeding behavior of the zebrafish. The purpose was also to do high throughput screening of antiobesity drug with this method and to study how genes affect feeding. The amount of food that zebrafish ate was able to be measured by utilizing fluorescent rotifers as fish's food. Drugs that are known to affect feeding (fluoxetine and rimonabant) reduced the amount of food zebrafish ate when measurement was done in 6-well plate and with two hours feeding. Sibutramine did not affect food intake, although it has been shown to reduce food intake in zebrafish in another study. The effect of gene knock down was also studied with morpholino oligonucleotides. MANF, th2 or galanin gene knock down did not affect food intake in zebrafish. The conclusion is that the new method is well suited for food intake measurements and drug effectiveness studies. The method can not be used in high throughput screening because results can not be analyzed by a plate reader and the feeding can not be done in 96-well plate.

Myelin is a lipid-rich substance wrapped around nerve axons that can be adaptively modified in response to neuronal activity and experience. Recent research has revealed myelination of parvalbumin (PV) inhibitory interneurons, critical for brain oscillations and balance. Defects in PV interneuron myelination have been linked to psychiatric disorders, like schizophrenia. Tropomyosin receptor kinase B (TrkB) signaling has been shown to be important for myelination. Moreover, fluoxetine, an antidepressant, binds to TrkB receptors in PV interneurons, enhancing plasticity. While previous studies support the importance of PV interneuron mediated TrkB signaling for anti-depressant induced neural plasticity, its effect on PV interneuron myelination remains unexplored. The objective of this thesis was to investigate whether TrkB signaling, and fluoxetine affect the overall and PV-interneuron specific myelination in the medial prefrontal cortex (mPFC) in mice. Using immunohistochemical analysis, we assessed myelin changes through node of Ranvier morphology and myelin immunostaining intensity in control and in mice with heterozygous conditional TrkB deletion in PV interneurons (hereafter referred to as TrkB KO), with or without fluoxetine. We found that fluoxetine increases node length in TrkB KO mice, while reduced TrkB signaling shortens paranodes in PV neurons compared to controls. Our findings also depict that fluoxetine and PV-mediated TrkB signaling do not alter the overall myelination of the mPFC. The findings of this work provide mechanistic insights into PV interneuron myelination in the mPFC, with potential implications for demyelinating and psychiatric conditions where PV myelination plays a role.