Effects of a constant light environment on hippocampal neurogenesis and memory in mice
ABSTRACT Because the environmental light-dark cycle is a key factor involved in modulating circadian rhythm in mammals, disruption of cyclic light conditions has a variety of effects on physiology and behavior. In the hippocampus, neurogenesis, which continues to occur throughout life, has been reported to exhibit circadian variation under cyclic light-dark conditions. In the present study, we examined whether a constant light environment affected hippocampal neurogenesis in mice. Half of the animals were exposed to continuous light conditions (L/L group), while the other half remained under normal cyclic light-dark conditions (L/D group). In the L/L group, the number of BrdU-labeled cells (proliferating cells) and that of BrdU and class III β-tubulin double-labeled cells (newborn neurons) in the granule cell layer were significantly decreased compared with the L/D group. Because hippocampal neurogenesis is involved in memory and learning, we also investigated the effects on performance in water maze tasks to assess spatial learning. Exposure to L/L treatment for 3 weeks impaired spatial learning task performance, although there was no difference in the open field behaviors between the groups. These findings demonstrate that the constant light conditions impaired hippocampal neurogenesis as well as cognitive performance, and suggest an important role for the cyclic light-dark environment in appropriate maintenance of the hippocampal system.
SourceAvailable from: Cesar Acevedo-Triana[Show abstract] [Hide abstract]
ABSTRACT: Se reconoce que el ejercicio puede aumentar la neurogénesis adulta y este fenómeno podría evidenciarse en diferentes niveles (comportamental, celular, electrofisiológico). El objetivo del estudio fue evaluar el efecto de la estimulación de la neurogénesis hipocampal mediante el ejercicio, sobre la memoria de trabajo evaluada mediante una tarea de laberinto en T en ratas macho adultas de la sepa Wistar. Se utilizó un diseño experimental de dos grupos en el cual un grupo experimental GE (n = 12) fue sometido a un programa de ejercicio forzado durante 5 días, al mismo tiempo que se administró un marcador de síntesis de ADN (Bromo-deoxi-uridina [BrdU](50 mg/kg IP.), los animales control GC (n = 9) no fueron expuestos al ejercicio pero se les administró igual dosis de BrdU. Tres (3) animales (GE = 2; GC = 1) se sometieron a cirugía de implantación de electrodos en la corteza frontal medial (+3,0 mm AP; ± 0.5 mm ML; -3.0mm DV) e hipocampo (-3.0mm AP; ± 1.8mm ML; -3.5mm DV) para registro electroencefalográfico durante la ejecución en el laberinto en T. 6-8 semanas después de la aplicación del ejercicio se evaluó la memoria de trabajo en laberinto en T y se analizaron cuatro (4) días de elección evaluando la alternancia de las opciones como indicador de memoria de trabajo. No se encontró diferencia comportamental entre los grupos experimental y control en variables comportamentales (alternancia, índice de preferencia, tiempo de respuesta, tiempo de ensayo, consumo de comida). El registro electroencefalográfico de los animales no mostró una tendencia a la coherencia entre las áreas registradas, siendo éste un indicador fisiológico del proceso de elección. En cuanto a la cantidad de nuevas neuronas no se encontraron diferencias por grupos.12/2014, Degree: Master, Supervisor: Fernando Cardenas; Manuel Rojas
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ABSTRACT: Circadian rhythm disruptions are often observed in depressed patients, and changes in the light/dark cycle promote depressive-like behavior in animal models. Prolonged exposure to constant light (LL) is known to lead to arrhythmicity of circadian locomotor activity and depressive-like behavior in rats. Interestingly, neonatal exposure to LL prevents both arrhythmicity and depressive behavior in adulthood. Arrhythmic rats under LL conditions that cohabitate with a rhythmic rat exhibit improvement in circadian rhythms. We tested whether such cohabitation also protects against LL-induced depressive-like behavior. Wistar rats were assigned to conditions of either neonatal constant light (neonatal-LL) on postnatal days 10-22 or a regular light/dark cycle (neonatal-LD). On day 45, the animals were assigned to three possible pair combinations. After a baseline sucrose preference test, half of the pairs were placed under LL conditions. Weekly sucrose preference tests were conducted to evaluate depressive-like behavior. The animals were isolated by an aluminum wall on the test day. At week 2 of LL, sucrose preference was reduced in neonatal-LD/neonatal-LD pairs of animals. At week 5, neonatal-LD/neonatal-LD pairs exhibited anhedonic-like behavior, but the pairs with at least one neonatal-LL rat did not. The LL cycle was returned to an LD cycle, and the neonatal-LD/neonatal-LD pairs exhibited a restoration of sucrose preference 2 weeks later. We conclude that social interaction can prevent depressive-like behavior induced by circadian rhythm disruption as long as one of the animals is more prone to present a strong rhythm. Copyright © 2014. Published by Elsevier Ireland Ltd.Neuroscience Letters 12/2014; 588. DOI:10.1016/j.neulet.2014.12.042 · 2.06 Impact Factor
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ABSTRACT: Nitric oxide (NO) is one of the most important interneural signaling molecules mediating hippocampal functions for learning and memory. The diurnal expression of neuronal NO synthase (nNOS) has been well studied. However, the temporal profile and underlying mechanisms of inducible NOS (iNOS) expression in a normal photoperiod or in altered light-dark cycles remain unclear. We examined the temporal profile of iNOS expression in adult male Sprague-Dawley rats maintained in a 12h-light/ 12h-dark photoperiod (12L/12D), which were pre-synchronized for 7 days before the experiment. The protein and mRNA levels of iNOS in the cortex and hippocampus were measured to examine the photic influences on iNOS expression. The results showed rhythmically changes of the levels of iNOS mRNA and protein in the hippocampus, but not in the cerebral cortex. The iNOS mRNA levels peaked at Zeitgeber time (ZT) 6 and ZT22, and the protein levels peaked at ZT8 and ZT18. Notably, the peaks in iNOS mRNA and protein levels in the 12L/12D group were 10 to 12 h apart, and the rhythmic pattern was absent in the 24-h period of the darkness group. In addition, the level of the phosphorylated cAMP response element binding protein (phospho-CREB) was the highest at ZT18, prior to a peak in iNOS mRNA expression at ZT22. A phospho-CREB-iNOS signaling pathway was further confirmed by the interaction of phospho-CREB and the iNOS DNA in histone complexes isolated by chromatin immunoprecipitation at ZT18. In conclusion, the photoperiod affects the diurnal expression of iNOS and activation of CREB in the hippocampus, which provide clues for the possible impact of circadian changes in hippocampal functions.