ABSTRACT
Objective To investigate the effects of dorsal hippocampal lesions (DH) or fimbria-fornix transection (FF) on the learning and memory of conditioned fear and the heart rate and blood pressure in rats.Methods Nineteen male adult Wistar rats were used in this experiment.They were implanted telemetry sensors in their abdominal aortas.Two week later,six of the rats were subjected to permanent NMDA-induced neurotoxic lesions to the dorsal hippocampus (DH) and seven for the fimbria-fornix transection (FF)through stereotactic brain surgery,the left six were treated with saline as the control (Sham).All rats were subjected to a conditioned fear experiment.Meanwhile,changes in heart rate and blood pressure were measured.Results There was no significant difference in heart rate and blood pressure among the rats with the hippocampal operation or fimbria-fornix transection.In the acquisition of conditioned fear,there were significant difference in freezing time among the three group in both inter-trial-interval (ITI) and conditioned stimulus (CS) process (all P＜0.05).The freezing time of the FF group showed significantly lower than that of the Sham group (P＜0.05).There was no significant difference in heart rate and blood pressure among the three group(P＞0.05).In the test of conditioned contextual fear memory,the freezing time percentage in the FF group ((0.31±0.16) ％) significantly lower than that in the Sham group ((2.78± 1.23) ％) (P＜0.05)at the first 3 min of the test.There was a significant difference in heart rate among the three group.The heart rate of FF group ((436.42± 10.16) times/min) was significantly lower than that of the Sham group ((472.48±4.43) times/min,P＜0.01) and the DH group ((469.94 ±7.36)times/min,P＜0.01).In the test of conditioned tone fear memory.The freezing time percentage in FF group ((18.78±6.29) ％) was significantly lower than that in the Sham ((51.77±9.33)％,P＜0.01) and DH group ((59.19±8.13)％,P＜0.01),but the freezing time percentage between the later two groups had no difference (P=0.52).The synchronous telemetry measurement showed there was no significant difference both in the heart rate and the blood pressure among the groups (all P＞0.05) during the conditioned tone test.Conclusion The dorsal hippocampal lesions and fimbria-fornix transection in rats can significantly reduce the learning and memory ability in conditioned fear and scene fear in rats,and the effect of fimbria-fornix transection is more obvious.The decrease in,fear memory is not synchronously reflected in heart rate and blood pressure in rats.
ABSTRACT
Las vitaminoterapias han sido ampliamente utilizadas en neurología para el tratamiento de neuritis o la correción de déficit metabólicos. En Cuba, se produce desde hace algunos años el preparado vitamínico Compvit®, que contiene vitaminas B1, B6 y B12. El ácido orótico, también llamado vitamina B13, es un producto natural que ha mostrado acciones como nootrópico en estudios con animales jóvenes y viejos que acusan deterioro cognitivo. En el presente trabajo se reportan los resultados de un estudio realizado para evaluar las potencialidades terapéuticas del Compvit® y del ácido orótico, empleando la lesión del sistema fimbria-fornix, que afecta severamente las capacidades de aprendizaje de los animales. Los resultados confirman un efecto positivo de cada uno de los tratamientos vitamónicos mejorando las capacidades cognitivas afectadas por la lesión. Aunque ninguno de los productos empleados o su combinación fue capaz de elevar el rendimiento cognitivo al nivel de los animales sanos, todos logran mejorías signficativas en comparación con el placebo. Este trabajo constituye una evidencia adicional en favor del uso terapéutico de compuestos vitamínicos como parte del tratamiento neurorrestaurativo
Vitamin therapies have been widely used in Neurology for the treatment of neuritis or the correction of metabolic deficits. In Cuba, Compvit® (B1, B6 and B12 vitamins) have been produced since several years. Orotic acid, also called vitamin B13 is a natural product showing nootropic actions in studies with young and old cognitively impaired animals. The present paper reports the results of a study conducted to assess the therapeutic potentials of Compvit® and orotic acid, in the recovery of cognitive abilities in fimbria-fornix lesioned animals, a lesion known to severely impair learning abilities. The results confirm positive effects of each vitamin treatment to improve the cognitive abilities affected by lesion. Although none of the products used, neither their combination, was able to raise the cognitive performance to the level of non-lesioned animals, both of them achieve significant improvement compared to placebo. The present paper constitutes additional evidence favoring the therapeutic use of vitamin compounds as part of neurorestorative treatments
ABSTRACT
Objective To investigate the effect of extracellular signal-regulated kinases(ERK) signal transduction in the process of NSCs differentiating into neurons in the fimbria-transected hippocampi's extracts. Methods Twelve Sprague-Dawley rats'right fimbrias were transected. The extracts were gained from the fimbria-transected hippocampi at the 14th day normal rat, and the extracts supernatant fluid was collected after centrifugal process, then the protein concentration in the extracts was determined. In the serum-free medium,NSCs from the fetal hippocampus were planted on 24 well culture plate, then were divided into three group and eight wells for each group as follows: the transected group contained the extracts of the fimbria-transected hippocampi;the normal group contained the extracts of the normal hippocampi;the pure control group have no extracts. After cultured for 14 days,the cells were detected by using MAP-2 and p-ERK immunofluorescence. Result The number, area, perimeter of MAP-2 positive neurons were all declined in transected group, the normal group and the control group orderly. Statistic results showed significant difference between every two groups. The number of MAP-2/p-ERK double-positive neurons were decreased in transected group, the normal group and the control group orderly, but the percentage of double-labeled neurons in total MAP-2 positive neurons were increased in turn. In these two aspect, there were also significant difference between every two group. And most of the MAP-2/p-ERK double-positive neurons were immature. Conclusion The extracts of the fimbria-transected hippocampi had obvious effects on promoting NSCs differentiating into neurons and speeding up the maturation of neurons than those of the normal hippocampi. The morphological results showed that ERK signal transduction might be related to the differentiation of NSCs into neurons.
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Objective To investigate the difference of Brn-4 mRNA expression between the fimbria/fornix-transected rats and normal ones. Methods Forty-two SD rats were randomly divided into 7 groups,6 rats in each group.One group served as normal control and the others served as fimbria/fornix transected 1st,3rd,7th,14th,21st and 28th day group,respectively.Then hippocampi were isolated and total RNA was extracted.Semi-quantitative reverse transcriptase-polymerase chain reaction(RT-PCR) method was used in detection of the expression change of Brn-4 mRNA in hippocampus after fimbria/fornix transection.Results The expression level of Brn-4 mRNA started to increase on the 3 days after fimbria/fornix transection.The peak appeared on the 14 days,then decreased slowly to pre-transection level on the 28 days.Conclusion The process that the expression of Brn-4 mRNA increases significantly after fimbria/fornix transection,perhaps,might be related to the transplanted neural stem cells(NSCs) differentiating into neurons and AChE positive neurons in hippocampus.