Maria Gabriela Menezes Oliveira

SPATIAL MEMORY IS IMPROVED BY AEROBIC AND RESISTANCE EXERCISE THROUGH DIVERGENT MOLECULAR MECHANISMS

A growing body of scientific evidence indicates that exercise has a positive impact on human health, including neurological health. Aerobic exercise, which is supposed to enhance cardiovascular functions and metabolism, also induces neurotrophic factors that affect hippocampal neurons, thereby improving spatial learning and memory. Alternatively, little is known about the effect of resistance exercise on hippocampus-dependent memory, although this type of exercise is increasingly recommended to improve muscle strength and bone density and to prevent age-related disabilities. Therefore, we evaluated the effects of resistance training on spatial memory and the signaling pathways of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1), comparing these effects with those of aerobic exercise. Adult male Wistar rats underwent 8 weeks of aerobic training on a treadmill (AERO group) or resistance training on a vertical ladder (RES group). Control and sham groups were also included. After the training period, both AERO and RES groups showed improved learning and spatial memory in a similar manner. However, both groups presented distinct signaling pathways. Although the AERO group showed increased level of IGF-1, BDNF, TrkB, and β-CaMKII (calcium/calmodulin-dependent kinase II) in the hippocampus, the RES group showed an induction of peripheral and hippocampal IGF-1 with concomitant activation of receptor for IGF-1 (IGF-1R) and AKT in the hippocampus. These distinct pathways culminated in an increase of synapsin 1 and synaptophysin expression in both groups. These findings demonstrated that both aerobic and resistance exercise can employ divergent molecular mechanisms but achieve similar results on learning and spatial memory.

Antiulcerogenic effects of two Maytenus species in laboratory animals.

Leaves of Maytenus species are commonly used in Brazil for the treatment of gastric ulcers, dyspepsias and other gastric problems. The present study evaluated the antiulcerogenic potential of a boiling water extract of equal parts of M. aquifolium and M. ilicifolia leaves against ulcer lesions induced by indomethacin and cold-restraint stress in rats. Ranitidine and cimetidine were used as reference drugs. The oral and intraperitoneal administration of the extract had a potent antiulcerogenic effect against both types of ulcers. The extract was shown to cause an increase in volume and pH of gastric juice of the animals with the pH effects comparable to those of cimetidine. The results tend to confirm the popular use of the plant.

Strategies used by hippocampal- and caudate-putamen-lesioned rats in a learning task.

In rats, hippocampal lesions result in impairment of spatial navigation, although other learning abilities remain unaltered. When learning a left/right discrimination task, rats can use a spatial strategy (with external maze landmarks-Situation 1) or are forced to use an egocentric strategy (without external or internal maze cues-Situation 2). Little is known about the extrahippocampal systems involved in the utilization of egocentric strategy. It is suggested that striatum could play an important role in the learning abilities that are spared after hippocampal lesion. The aim of our study was to investigate which strategy is used by rats bearing hippocampal or caudate-putamen lesions in the acquisition of a left/right discrimination task in an elevated T-maze in both Situations 1 and 2. We also investigated the effect of each lesion on the reversal of discrimination in both situations. Acquisition was not altered in any of the situations; however, a transfer test showed that hippocampal-lesioned rats used a different strategy (egocentric) from control animals (spatial) in Situation 1. In addition, reversal of the discrimination was impaired in Situation 2. Caudate-putamen lesion produced a transient effect on reversal of discrimination only in the egocentric task (Situation 2), but did not impair acquisition of the task in either situation, thus suggesting that the animals were able to use either strategy.

Sensitization to ethanol's stimulant effect is associated with region-specific increases in brain D2 receptor binding

Abstract  Rationale: Stimulation of locomotor activity by low doses of ethanol (EtOH) and the potentiation of this response after repeated administration (sensitization) have been related to EtOH’s rewarding and addictive properties and to altered dopaminergic activity in brain. In mice, behavioral sensitization to EtOH occurs only in a subset of treated animals, and this provides an opportunity for distinguishing general drug effects from sensitization-specific brain effects. Objectives: In view of evidence suggesting a role for dopamine D2 receptors in EtOH preference and abuse liability, the present study addressed the hypothesis that D2 binding would be altered in specific brain regions in mice showing differential sensitization responses to chronic EtOH administration. Methods: Male albino Swiss mice received 2.4 g/kg EtOH i.p. daily for 21 days and were then separated into sensitized or non-sensitized subgroups on the basis of weekly locomotor activity tests. Results: Autoradiographic analyses of [3H]raclopride binding to D2 sites revealed significant increases in the anterior caudate-putamen of mice in the EtOH-sensitized group when compared with either saline controls (+40%, P<0.00009) or to mice in the EtOH non-sensitized group (+32%; P<0.0003). Smaller increases were seen in the ventrolateral caudate-putamen of sensitized animals (+18% vs control, P<0.02; and 12% vs non-sensitized mice, P<0.07). No differences were found in other brain regions, including the nucleus accumbens, olfactory bulb and substantia nigra. Conclusions: The observed increases in D2-receptor binding in circumscribed targets of nigrostriatal projections may reflect either a pre-existing condition in sensitization-prone animals or a selective vulnerability of D2 receptors to chronic EtOH in these animals. In either case, it may be a marker for differential susceptibility to EtOH sensitization.

Recognition memory for emotional pictures in Alzheimer's patients

Objective– The purpose of the present study was to examine whether Alzheimer’s Disease (AD) patients can benefit from the emotional content of visual stimuli in a picture recognition test. Method– Sixteen patients with AD and 19 normal controls matched for age and years of education, were studied. Sixteen pictures (with varying emotional contents) were presented to each participant. Thirty minutes later, a recognition test was applied with the target‐pictures mixed among 34 others of similar content. The subjects were instructed to rate them as pleasant, unpleasant or indifferent. Results– The total of pictures correctly recognized by the AD patients (75.4% of the target‐pictures) was smaller than that of the controls (96.4%). Controls recognized more emotional pictures than indifferent pictures. Conclusions– Emotional content enhanced recognition of pictures in normal subjects, whereas for the Alzheimer’s subjects the emotional significance attached to the pictures was of no benefit to enhance recognition.

Anterior thalamus deep brain stimulation at high current impairs memory in rats

Deep brain stimulation (DBS) of the anterior thalamic nucleus (AN), an important relay in the circuitry of memory, is currently being proposed as a treatment for epilepsy. Despite the encouraging results with the use of this therapy, potential benefits and adverse effects are yet to be determined. We show that AN stimulation at relatively high current disrupted the acquisition of contextual fear conditioning and impaired performance on a spatial alternating task in rats. This has not been observed at parameters generating a charge density that approximated the one used in clinical practice. At settings that impaired behavior, AN stimulation induced a functional depolarization block nearby the electrode, increased c-Fos expression in cerebral regions projecting to and receiving projections from the AN, and influenced hippocampal activity. This suggests that complex mechanisms might be involved in the effects of AN DBS, including a local target inactivation and the modulation of structures at a distance. Though translating data from animals to humans has to be considered with caution, our study underscores the need for carefully monitoring memory function while selecting stimulation parameters during the clinical evaluation of AN DBS.

Dissociated paradoxical sleep deprivation effects on inhibitory avoidance and conditioned fear

Rats were submitted to paradoxical sleep deprivation (PSD) for 24, 72, or 96 h and were trained on a double aversively motivated task, encompassing a step-through inhibitory avoidance and a classical conditioning of fear to a brief tone serving as conditional stimulus. Retention test of the inhibitory avoidance was performed at the same apparatus of training (without tone presentation). Retention of conditioned fear was assessed in an open field apparatus, where the freezing reaction to the tone was measured. PSD for 24 and 72 h preceding the training session had no effect on either task. However, PSD during the 96 h preceding the training session impaired acquisition of inhibitory avoidance, but had no effect on classically conditioned fear. It is concluded that PSD had differential effects on the two tasks, both aversively motivated and trained at the same time and conditions.

Effects of dorsal striatum lesions in tone fear conditioning and contextual fear conditioning

It has been suggested that the striatum mediates hippocampus-independent memory tasks. Classical fear conditioning to a discrete stimulus such as a tone is not affected by hippocampal lesion, whereas contextual fear conditioning is an hippocampus dependent task. The purpose of the present study was to verify the effect of dorsal striatal lesions on tone and contextual fear conditioning. The lesioned rats were not impaired in contextual fear conditioning but in tone fear conditioning both electrolytically and neurotoxically lesioned animals showed less freezing compared with controls. The lesion effect was observed after a postoperative recovery period of 14 days but not after 2 months. The results support the hypothesis that the dorsal striatum is involved in hippocampus-independent memory tasks, but, in spite of this involvement, it does not seem to be a critical structure.

Social stress does not interact with paradoxical sleep deprivation-induced memory impairment

Extensive evidence has linked both paradoxical sleep (PS) and stress to memory processing. The purpose of the present study was to examine the effect of social instability stress on memory and to verify whether this stress interferes with the amnesic effect of PS deprivation using the modified multiple platform method. In addition to the PS-deprived group (put onto narrow platforms inside the deprivation tanks) two control groups were used: one of them remained in its home-cages and the other was placed inside the deprivation tanks, onto a grid that contained large platforms on it. All groups were subdivided in socially stable and unstable conditions. Immediately after 96 h of sleep deprivation, the animals were trained in three different memory tasks: inhibitory avoidance, classical fear conditioning to a discrete stimulus and contextual fear conditioning. Twenty-four hours after training, the animals were tested in order to assess task acquisition. The results showed that social instability did not impair the performance of animals nor interacted with PS deprivation in any of the tasks. Grid control animals presented a selective impairment in the inhibitory avoidance task and contextual, but not in the classical, fear conditioning task, compared to cage control rats. This finding could be due to the stress to which grid control animals were exposed (humidity and luminosity) during the manipulation period. PS-deprived animals exhibited poorer performance than the other groups in all tasks. As they also showed an increased threshold to shock-induced vocalisation, but not to flinch response, it is not possible to completely rule out a decreased response to noxious stimulation as a contributing factor for the present results with PS deprivation.

Behavioral changes resulting from the administration of cycloheximide in the pilocarpine model of epilepsy

Cycloheximide influences synaptic reorganization resulting from pilocarpine-induced status epilepticus (SE). To investigate the possible behavioral consequences of this effect, we subjected animals to pilocarpine-induced SE either in the absence (Pilo group) or presence of cycloheximide (Chx group). Animals were further divided regarding the occurrence of spontaneous recurrent seizures (SRS). Two months after SE induction animals were exposed to different behavioral tests. Age-matched naïve animals were used as controls. All epileptic groups showed a significantly diminished freezing time in contextual and tone fear conditioning, performed poorly in the Morris water maze and present less seconds in immobility position as compared to controls. Only Pilo animals explored more extensively the open arms of the elevated plus maze and showed increased in horizontal exploratory activity in the open field as compared to controls. With the exception of Pilo animals without recorded SRS, all other groups had extensive tissue shrinkage in central nucleus of the amygdala as compared to controls. Cycloheximide-treated animals differed from Pilo animals in the extent of hilar loss and supragranular mossy fiber sprouting as well as tissue shrinkage in the dorsal hippocampus. Despite the histological differences seen in the dorsal hippocampus between experimental groups, no differences were encountered in the cognitive tests used to evaluate dorsal hippocampal function. The encountered histological differences between Chx and Pilo animals, however, might underlie the different emotional responses between the two groups.