RESUMEN
Clinical findings reveal that middle-aged patients are more susceptible to suffer from psychiatric disorders than older ones. However, little is known about the emotional behavior of aging rodents. This study aimed to investigate behavioral alterations in male middle-aged Wistar rats in the open-field (OF) test (at illuminated and dimly light conditions), elevated plus maze (EPM), forced swimming (FST) and inhibitory avoidance task (IA). In the EPM, middle-aged rats displayed reduced percentages of the time spent in and entries into open arms. The ambulatory activity measured in the OF under dimly light conditions was identical among groups. However, under illuminated conditions, a reduction in the number of crossings was detected in older rats, reinforcing that aged animals display a genuine anxiogenic-like phenotype. Additionally, aged rats showed an increase in the immobility time in the FST, and a reduction in the latency to step down the platform in the IA. A negative correlation was found between the immobility time and latency to step down the platform, suggesting a relationship between depressive-behavior and cognitive impairment in old rats. Altogether, male middle-aged rats are more anxious, depressed, and display aversive memory impairments. These observations contribute to investigate biological mechanisms and therapeutic interventions for geriatric anxiety and depression.
Asunto(s)
Ansiedad/psicología , Depresión/psicología , Trastornos de la Memoria/psicología , Factores de Edad , Animales , Reacción de Prevención , Peso Corporal , Modelos Animales de Enfermedad , Inhibición Psicológica , Masculino , Aprendizaje por Laberinto , Actividad Motora , Ratas , Ratas Wistar , NataciónRESUMEN
Clinical and pre-clinical findings point to the critical role of ovarian hormones in modulating anxiety and depressive symptoms in female. However, few studies investigated the effects of long-term ovarian hormones withdrawal on animal behavior. The current study evaluated the behavioral effects of long-term ovariectomy (performed at 3 months of life) in adult (6 months old) and aged (18 months old) rats subjected to the elevated plus-maze and forced swimming tests. A substantial reduction in the time spent in open arms in adult and aged ovariectomized rats was observed compared to intact animal from the same age. A significant increase in the immobility time was observed in aged rats, ovariectomized or not, compared to adult rats. It should be noted that no alterations in the spontaneous locomotion were detected among groups. In addition, a reduction in serum concentrations of 17beta-estradiol was observed in adult ovariectomized and aged sham and ovariectomized rats compared to adult intact animals. Taken together, these findings suggest that anxiety-related behaviors were affected by ovariectomy, but not aging. However, the depressive-like behavior observed in aged rats seems to be much more influenced by senescence than ovarian hormones withdrawal. The presented results are discussed considering the effects of gradual and abrupt reduction of ovarian steroids concentrations, and the influence of aging on behavior of female rats.
Asunto(s)
Ansiedad/fisiopatología , Síntomas Conductuales/fisiopatología , Ovariectomía , Factores de Edad , Análisis de Varianza , Animales , Ansiedad/sangre , Conducta Animal , Síntomas Conductuales/sangre , Peso Corporal/fisiología , Modelos Animales de Enfermedad , Estradiol/sangre , Conducta Exploratoria/fisiología , Femenino , Aprendizaje por Laberinto , Radioinmunoensayo , Ratas , Ratas Wistar , Natación , Vagina/patologíaRESUMEN
Glutamate increases the extracellular adenosine levels, an important endogenous neuromodulator. The neurotoxicity induced by glutamate increases the ecto-5'-nucleotidase activity in neurons, which produces adenosine from AMP. L- and D-aspartate (Asp) mimic most of the actions of glutamate in the N-methyl-D-aspartate (NMDA) receptors. In the present study, both amino acids stimulated the ecto-5'-nucleotidase activity in cerebellar granule cells. MK-801 and AP-5 prevented the L- and D-Asp-evoked activation of ecto-5'-nucleotidase. Both NMDA receptor antagonists prevented completely the damage induced by L-Asp, but partially the D-Asp-induced damage. The antagonist of adenosine A(2A) receptors (ZM 241385) prevented totally the L- Asp-induced cellular death, but partially the neurotoxicity induced by D-Asp and the antagonist of adenosine A(1) receptors (CPT) had no effect. The results indicated a different involvement of NMDA receptors on the L- or D-Asp-evoked activation of ecto-5'-nucleotidase and on cellular damage. The adenosine formed from ecto-5'-nucleotidase stimulation preferentially acted on adenosine A(2A) receptor which is probably co-operating with the neurotoxicity induced by amino acids.
Asunto(s)
5'-Nucleotidasa/metabolismo , Ácido Aspártico/metabolismo , Supervivencia Celular , Ácido D-Aspártico/metabolismo , Neuronas/enzimología , Neuronas/fisiología , Receptor de Adenosina A2A/metabolismo , Adenosina Monofosfato/metabolismo , Animales , Ácido Aspártico/química , Células Cultivadas , Cerebelo/citología , Ácido D-Aspártico/química , Ácido Glutámico/metabolismo , N-Metilaspartato/metabolismo , Neuronas/citología , Ratas , Ratas WistarRESUMEN
Ebselen is a selenium compound that have glutathione peroxidase-like activity which is neuroprotective in acute stroke ischemia. The efficacy of ebselen to prevent excitotoxicity provoked by glutamate in cerebellar granule neurons was investigated at various time points and concentrations. Simultaneous addition of ebselen with glutamate decreased neuronal death and was completely reversed by 3 microM of ebselen (3 (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and propidium iodide assays). However, when 1 microM of ebselen was added with glutamate and remained in the culture medium until 24 or 48 h, the neuronal survival increased to the control. The mechanism proposed for neuroprotection was the ability of ebselen to prevent lipoperoxidation provoked by glutamate. The present findings propose to amplify the use of ebselen in others neurodegenerative disorders involving glutamatergic system.
Asunto(s)
Antioxidantes/farmacología , Azoles/farmacología , Ácido Glutámico/metabolismo , Degeneración Nerviosa/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Neurotoxinas/metabolismo , Compuestos de Organoselenio/farmacología , Animales , Animales Recién Nacidos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas/citología , Células Cultivadas/efectos de los fármacos , Células Cultivadas/metabolismo , Corteza Cerebelosa/citología , Corteza Cerebelosa/efectos de los fármacos , Corteza Cerebelosa/metabolismo , Relación Dosis-Respuesta a Droga , Ácido Glutámico/farmacología , Isoindoles , Peroxidación de Lípido/efectos de los fármacos , Peroxidación de Lípido/fisiología , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/fisiopatología , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/fisiopatología , Neurotoxinas/farmacología , Ratas , Ratas WistarRESUMEN
Several enzymes hydrolyze ATP, producing ADP which is hydrolyzed to AMP. Ecto-5'-nucleotidase produces adenosine from AMP. Glutamate (Glu) is an excitatory neurotransmitter and increases extracellular adenosine levels, which is considered an important inhibitory neuromodulator. Here we show that Glu activates ADP and AMP hydrolysis. NMDA and kainic acid (KA) also increased these enzymatic activities, but 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) had no effect. Dihydrokainate (DHK), an inhibitor of glutamate uptake, also blocked glutamate-evoked activation of ecto-nucleotidases, suggesting that this activation was also Glu transporters dependent. Therefore, we suggest that the Glu-evoked stimulation of ecto-nucleotidases might contribute to the increase of adenosine in extracellular space induced by Glu.