RESUMEN
OBJECTIVE: Disturbances in hippocampal neurogenesis may be involved in the pathophysiology of depression and it has been argued that an increase in the generation of new nerve cells in the hippocampus is involved in the mechanism of action of antidepressants. MATERIALS AND METHODS: Adult Wistar rats were treated with fluoxetine (10 mg/kg) 1 h, daily for 5 (subchronic) or 28 days (chronic) before the Novelty Suppressed Feeding test was performed. Cell proliferation and neurogenesis were analysed using the markers 5-bromo-deoxy-2'-uridine, Ki-67, and doublecortin. RESULTS: A significant behavioural effect was found after 28 days of fluoxetine administration. However, no behavioural improvement was demonstrated after acute and subchronic treatment with fluoxetine. We further demonstrate that chronic antidepressant treatment increases cell proliferation as well as neurogenesis in the dentate gyrus, here using Wistar rats. CONCLUSIONS: In further development of antidepressants, neurogenesis may serve as an important parameter to examine the efficacy and mechanism of action of novel drugs.
Asunto(s)
Conducta Animal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fluoxetina/administración & dosificación , Neuronas/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Animales , Bromodesoxiuridina/metabolismo , Recuento de Células , Giro Dentado/citología , Proteínas de Dominio Doblecortina , Proteína Doblecortina , Esquema de Medicación , Conducta Alimentaria/efectos de los fármacos , Antígeno Ki-67/metabolismo , Masculino , Proteínas Asociadas a Microtúbulos/metabolismo , Neuropéptidos/metabolismo , Ratas , Ratas Wistar , Tiempo de Reacción/efectos de los fármacosRESUMEN
A study was performed to characterize dark brown or black discoloured kidneys ("black kidneys") in Danish slaughter cattle and to investigate the aetiology and pathogenesis. In 133 939 cattle entering four abattoirs, 359 cases of "black kidneys" were recorded. Of these, 57 cases were submitted for macroscopical, microscopical, and ultrastructural examination. A pigment with characteristics similar to those of lipofuscin was found in secondary lysosomes in epithelial cells of the proximal tubules. Pigment accumulation was the cause of discoloration, with a positive correlation between the discoloration of the renal cortex and the degree of pigment accumulation. Cases occurred only in cattle of the Holstein breed or the Red Danish Dairy breed and mainly in animals aged 3 years or older. In these breeds, prevalences of 0.44% and 2.51% were found, respectively. Epidemiological analyses indicated that affected animals aged 4.5 to 6.5 years or 7.5 to 8.5 years were culled more frequently than unaffected cattle. Epidemiological and genealogical analyses strongly indicated a genetic aetiology with simple autosomal recessive inheritance.