RESUMEN
Rising neurodegenerative and depressive disease prevalence combined with the lack of effective pharmaceutical treatments and dangerous side effects, has created an urgent need for the development of effective therapies. Considering that these disorders are multifactorial in origin, treatments designed to interfere at different mechanistic levels may be more effective than the traditional single-targeted pharmacological concepts. To that end, an experimental diet composed of zinc, melatonin, curcumin, piperine, eicosapentaenoic acid (EPA, 20:5, n-3), docosahexaenoic acid (DHA, 22:6, n-3), uridine, and choline was formulated. This diet was tested on the olfactory bulbectomized rat (OBX), an established animal model of depression and cognitive decline. The ingredients of the diet have been individually shown to attenuate glutamate excitoxicity, exert potent anti-oxidant/anti-inflammatory properties, and improve synaptogenesis; processes that all have been implicated in neurodegenerative diseases and in the cognitive deficits following OBX in rodents. Dietary treatment started 2 weeks before OBX surgery, continuing for 6 weeks in total. The diet attenuated OBX-induced cognitive and behavioral deficits, except long-term spatial memory. Ameliorating effects of the diet extended to the control animals. Furthermore, the experimental diet reduced hippocampal atrophy and decreased the peripheral immune activation in the OBX rats. The ameliorating effects of the diet on the OBX-induced changes were comparable to those of the NMDA receptor antagonist, memantine, a drug used for the management of Alzheimer's disease. This proof-of-concept study suggests that a diet, which simultaneously targets multiple disease etiologies, can prevent/impede the development of a neurodegenerative and depressive disorders and the concomitant cognitive deficits.
Asunto(s)
Trastornos del Conocimiento/dietoterapia , Trastornos del Conocimiento/tratamiento farmacológico , Memantina/uso terapéutico , Enfermedades Neurodegenerativas/dietoterapia , Enfermedades Neurodegenerativas/tratamiento farmacológico , Nootrópicos/uso terapéutico , Animales , Atrofia/dietoterapia , Atrofia/tratamiento farmacológico , Atrofia/patología , Atrofia/fisiopatología , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Trastorno Depresivo , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/fisiopatología , Masculino , Trastornos de la Memoria/dietoterapia , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/patología , Trastornos de la Memoria/fisiopatología , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/fisiopatología , Neuroinmunomodulación/efectos de los fármacos , Neuroinmunomodulación/fisiología , Fármacos Neuroprotectores/uso terapéutico , Trastornos del Olfato/patología , Trastornos del Olfato/fisiopatología , Bulbo Olfatorio/fisiopatología , Agitación Psicomotora/dietoterapia , Agitación Psicomotora/tratamiento farmacológico , Agitación Psicomotora/patología , Agitación Psicomotora/fisiopatología , Ratas , Ratas Sprague-Dawley , Percepción Espacial/efectos de los fármacos , Percepción Espacial/fisiología , Sulfato de ZincRESUMEN
The serotonin transporter (SERT) plays a crucial role in anxiety. Accordingly, variance in SERT functioning appears to constitute an important pathway to individual differences in anxiety. The current study tested the hypothesis that genetic variation in SERT function is associated with variability in the basic reflex physiology of defense. Healthy subjects (N=82) were presented with clearly instructed cues of shock threat and safety to induce robust anxiety reactions. Subjects carrying at least one short allele for the 5-HTTLPR polymorphism showed stronger fear-potentiated startle compared to long allele homozygotes. However, short allele carriers showed no deficit in the downregulation of fear after the offset of threat. These results suggest that natural variation in SERT function affects the magnitude of defensive reactions while not affecting the capacity for fear regulation.
Asunto(s)
Miedo/fisiología , Polimorfismo Genético , Reflejo de Sobresalto/genética , Reflejo/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Estimulación Acústica , Adolescente , Adulto , Alelos , Ansiedad/genética , Señales (Psicología) , Femenino , Genotipo , Humanos , MasculinoRESUMEN
RATIONALE: Early life stress is a risk factor for the development of psychopathology in later life. Consequences of adverse life events, however, may depend on the genetic makeup of an individual. Reduced serotonin(1A) receptor function may predispose to the development of anxiety disorders. OBJECTIVE: Determine susceptibility of serotonin(1A) receptor knockout (1AKO) mice on different background strains to the effects of maternal separation (MS) by assessing startle plasticity in adulthood. METHODS: 1AKO mice on a 129S6 and a Swiss Webster (SW) background were used. MS groups were separated daily from their mother for 180 min/day from postnatal days 2 to 14. Control groups underwent normal animal facility rearing. In adulthood, effects on acoustic startle response, habituation, prepulse inhibition (PPI), and foot shock sensitization were determined. RESULTS: MS increased startle reactivity and reduced PPI in 129S6 mice. These effects of MS were independent of genotype. MS had no effect on the other readouts. In SW mice, MS had no consistent effect on startle reactivity and did not alter startle plasticity in wild type or in 1AKO mice. 1AKO mice did not differ from wild-type mice in startle plasticity. CONCLUSION: Serotonin(1A) receptor deletion does not enhance vulnerability to the effects of MS on startle plasticity. The life-long increase in startle reactivity and PPI deficit induced by MS are strain-dependent. Further, the use of startle reactivity and plasticity may have added value in translational studies relating to early life stress.
Asunto(s)
Privación Materna , Receptor de Serotonina 5-HT1A/genética , Reflejo de Sobresalto , Estrés Psicológico/complicaciones , Estimulación Acústica , Factores de Edad , Animales , Animales Recién Nacidos , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones NoqueadosRESUMEN
This unit describes the testing of sexual behaviors of male Wistar rats. The described test enables the detection of stimulatory and inhibitory profiles of compounds. The test includes four training sessions to reach a stable sexual performance, followed by acute and/or chronic administration of drugs. The main quantifiable sexual behaviors are number of mounts (no vaginal penetration), intromissions (vaginal penetration), and ejaculations. By comparing the test compound to reference compound(s), sexual (side) effects can be determined.