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1.
Br J Pharmacol ; 171(20): 4767-84, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24866852

ABSTRACT

Eating disorders, such as anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorders (BED), are described as abnormal eating habits that usually involve insufficient or excessive food intake. Animal models have been developed that provide insight into certain aspects of eating disorders. Several drugs have been found efficacious in these animal models and some of them have eventually proven useful in the treatment of eating disorders. This review will cover the role of monoaminergic neurotransmitters in eating disorders and their pharmacological manipulations in animal models and humans. Dopamine, 5-HT (serotonin) and noradrenaline in hypothalamic and striatal regions regulate food intake by affecting hunger and satiety and by affecting rewarding and motivational aspects of feeding. Reduced neurotransmission by dopamine, 5-HT and noradrenaline and compensatory changes, at least in dopamine D2 and 5-HT(2C/2A) receptors, have been related to the pathophysiology of AN in humans and animal models. Also, in disorders and animal models of BN and BED, monoaminergic neurotransmission is down-regulated but receptor level changes are different from those seen in AN. A hypofunctional dopamine system or overactive α2-adrenoceptors may contribute to an attenuated response to (palatable) food and result in hedonic binge eating. Evidence for the efficacy of monoaminergic treatments for AN is limited, while more support exists for the treatment of BN or BED with monoaminergic drugs.


Subject(s)
Anorexia , Binge-Eating Disorder , Disease Models, Animal , Animals , Anorexia/drug therapy , Anorexia/physiopathology , Anorexia/psychology , Binge-Eating Disorder/drug therapy , Binge-Eating Disorder/physiopathology , Binge-Eating Disorder/psychology , Dopamine/physiology , Eating/drug effects , Feeding Behavior/drug effects , Humans , Neurotransmitter Agents/therapeutic use , Norepinephrine/physiology , Serotonin/physiology
2.
Gene Ther ; 21(2): 205-11, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24385145

ABSTRACT

RNA interference (RNAi) is a powerful strategy for unraveling gene function and for drug target validation, but exogenous expression of short hairpin RNAs (shRNAs) has been associated with severe side effects. These may be caused by saturation of the microRNA pathway. This study shows degenerative changes in cell morphology and intrusion of blood vessels after transduction of the ventromedial hypothalamus (VMH) of rats with a shRNA expressing adeno-associated viral (AAV) vector. To investigate whether saturation of the microRNA pathway has a role in the observed side effects, expression of neuronal microRNA miR-124 was used as a marker. Neurons transduced with the AAV vector carrying the shRNA displayed a decrease in miR-124 expression. The decreased expression was unrelated to shRNA sequence or target and observed as early as 1 week after injection. In conclusion, this study shows that the tissue response after AAV-directed expression of a shRNA to the VMH is likely to be caused by shRNA-induced saturation of the microRNA pathway. We recommend controlling for miR-124 expression when using RNAi as a tool for studying (loss of) gene function in the brain as phenotypic effects caused by saturation of the RNAi pathway might mask true effects of specific downregulation of the shRNA target.


Subject(s)
Genetic Vectors/adverse effects , MicroRNAs/genetics , Neurons/metabolism , RNA, Small Interfering/pharmacology , Signal Transduction/drug effects , Animals , Dependovirus/genetics , Gene Expression Regulation , Genetic Vectors/administration & dosage , MicroRNAs/toxicity , Organ Specificity , RNA, Small Interfering/genetics , Rats , Rats, Wistar , Ventromedial Hypothalamic Nucleus/metabolism
3.
Int J Obes (Lond) ; 38(4): 610-8, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23884084

ABSTRACT

BACKGROUND: Rats that have restricted access to food at a fixed time point of the circadian phase display high levels of food anticipatory activity (FAA). The orexigenic hormone ghrelin has been implicated in the regulation of FAA. However, it is not known via which brain area ghrelin exerts this effect. Growth hormone secretagogue receptor 1a (GHS-R1a) is highly expressed in the hypothalamus, including the dorsomedial hypothalamus (DMH) and the ventromedial hypothalamus (VMH). These two hypothalamic areas have been reported to play a role in FAA. AIM OF THE STUDY: To examine the role of GHS-R1a signaling in the DMH and VMH in FAA. DESIGN: Adeno-associated virus expressing a shRNA directed against GHS-R1a was used to establish local knockdown of GHS-R1a in the DMH and VMH in rats. Rats were subsequently subjected to a restricted feeding schedule (RFS). RESULTS: Under ad libitum conditions, knockdown of GHS-R1a in the VMH increased food intake and body weight gain. In addition, GHS-R1a knockdown in VMH and DMH reduced body temperature and running wheel activity (RWA). When rats were subjected to a RFS, the main effect of GHS-R1a knockdown in both DMH and VMH was a decrease in RWA and an attenuation of body weight loss. Rats with knockdown of GHS-R1a in DMH and VMH showed a delay in onset of FAA. In addition, GHS-R1a knockdown in DMH resulted in a reduction of FAA amplitude. CONCLUSION: This is the first study to investigate the effect of local hypothalamic knockdown of GHS-R1a on FAA. Our results implicate hypothalamic GHS-R1a signaling in the regulation of FAA. Nevertheless, some FAA remained, suggesting that a distributed network of brain areas and signaling pathways is involved in the development of FAA.


Subject(s)
Eating , Feeding Behavior , Ghrelin/metabolism , Hypothalamus/metabolism , Receptors, Ghrelin/metabolism , Weight Gain , Animals , Body Temperature , Body Weight , Male , Rats , Rats, Wistar , Signal Transduction
4.
Tijdschr Diergeneeskd ; 111(23): 1185-8, 1986 Dec 01.
Article in Dutch | MEDLINE | ID: mdl-3810631

ABSTRACT

The recording of spinal action potentials following stimulation of peripheral nerves may be as useful in dogs as it was found to be as a diagnostic tool in man. Technique and results of electrospinograms in ten normal dogs are reported.


Subject(s)
Dog Diseases/physiopathology , Electrodiagnosis/veterinary , Spinal Cord Diseases/physiopathology , Spinal Cord/physiopathology , Action Potentials , Animals , Dogs
5.
Tijdschr Diergeneeskd ; 110(22): 947-53, 1985 Nov 15.
Article in Dutch | MEDLINE | ID: mdl-4082162

ABSTRACT

Based on a review of the literature physical and histological features of cryotherapy are discussed. The most common indications in small animals are reviewed.


Subject(s)
Cryosurgery/veterinary , Animals , Anus Diseases/surgery , Anus Diseases/veterinary , Bone Neoplasms/surgery , Bone Neoplasms/veterinary , Cryosurgery/methods , Head and Neck Neoplasms/surgery , Head and Neck Neoplasms/veterinary , Skin Neoplasms/surgery , Skin Neoplasms/veterinary
6.
Vet Q ; 7(3): 237-9, 1985 Jul.
Article in English | MEDLINE | ID: mdl-4049721

ABSTRACT

Arthroscopy is presented as a safe, non-invasive diagnostic technique in dogs with knee-joint lesions. Equipment, procedure, and indications are briefly described. Advantages and disadvantages are summarized.


Subject(s)
Arthroscopy/veterinary , Dog Diseases/diagnosis , Hindlimb , Lameness, Animal/etiology , Stifle , Anesthesia, General/veterinary , Animals , Arthroscopes , Arthroscopy/methods , Dogs
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