Biomedical subjects

Carla Dalmaz

Publications and source records attributed to Carla Dalmaz.

At least 19 recordsLinked to original sources

PubMed2006

Chronic lithium treatment has antioxidant properties but does not prevent oxidative damage induced by chronic variate stress.

This study evaluated the effects of chronic stress and lithium treatments on oxidative stress parameters in hippocampus, hypothalamus, and frontal cortex. Adult male Wistar rats were divided into two groups: control and submitted to chronic variate stress, and subdivided into treated or not with LiCl. After 40 days, rats were killed, and lipoperoxidation, production free radicals, total antioxidant reactivity (TAR) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were evaluated. The results showed that stress increased lipoperoxidation and that lithium decreased free radicals production in hippocampus; both treatments increased TAR. In hypothalamus, lithium increased TAR and no effect was observed in the frontal cortex. Stress increased SOD activity in hippocampus; while lithium increased GPx in hippocampus and SOD in hypothalamus. We concluded that lithium presented antioxidant properties, but is not able to prevent oxidative damage induced by chronic variate stress.

Animals↗

PubMed2006

Satiety assessment in neonatally handled rats.

We have previously demonstrated that neonatal handling increases sweet food ingestion. In the present study, we examined whether food intake, using different kinds of food, is altered in neonatally handled animals, with or without inducing satiety using a sucrose solution. Abdominal fat, glycemia and hormones linked to appetite including leptin, ghrelin and insulin were also measured. We tested palatable food consumption in the homecage to verify whether environmental cues could influence ingestion. Nests of Wistar rats were either (1) non-handled or (2) handled (10 min/day). Handling was performed on days 1-10 after birth. When adults, rats were habituated to sweet food (Froot Loops, Kellogg's) and to palatable fiber pellets (Fiber One), Nestlé). Sweet food consumption was increased in the neonatally handled group, when tested in the homecage, and also in the satiety experiment. These rats displayed a satiety curve when compared to the control group, which ate less but constantly. Handled rats exposed to a sucrose solution decreased sweet food ingestion, which did not occur in the control group. When exposed to a food with complex carbohydrates, these differences disappeared. There were no differences in body weight, abdominal fat or in glycemia, as well as no differences in plasma levels of insulin or leptin. However, ghrelin was decreased in neonatally handled rats. Neonatally handled rats demonstrated an increased consumption of sweet food, satiety responses to sucrose, as well as decreased levels of plasma ghrelin. It is possible that signaling mechanisms related to satiety, both peripherally and/or centrally may contribute to these behavioral findings.

Abdominal Fat↗

PubMed2006

The nociceptive response of stressed and lithium-treated rats is differently modulated by different flavors.

Pleasant and unpleasant flavors and odors can modulate pain perception, and the efficacy of sweet flavors in reducing pain seems to be related to its hedonic value. Chronic variate stress paradigm is a model of depression, and is suggested to induce anhedonia. We observed previously that lithium may prevent behavioral and neurochemical alterations induced by chronic stress; so we hypothesized that chronically stressed animals may present different nociceptive response to pleasant and unpleasant tastes that could be prevented by lithium treatment. Adult male Wistar rats were divided into four groups, control and stressed, treated or not with lithium. A Chronic Variate Stress paradigm was used, and lithium was added to the chow. After 40 days of treatment, the tail flick latency of the animals was evaluated, and rats were immediately placed in a box with access to a 5% acetic acid solution (acid flavor). After 5 min, tail flick latency was measured again. On the following day, animals were submitted to the same procedure, with the substitution of acetic acid by condensed sweet milk (sweet flavor). The stressed group was the only group who did not present analgesia after sweet taste exposition. All groups, except the control group, presented increased tail flick latency after exposition to the acid flavor. These results indicate that pleasant and unpleasant flavors present different relevance for the induction of antinociception in stressed animals, and the absence of sweet flavor-induced analgesia may represent an anhedonic effect of the chronic variate stress paradigm. On the other hand, perception of different flavors may be more prominent in animals treated with lithium.

Animals↗

PubMed2005

Activation of adenosine A(1) receptors alters behavioral and biochemical parameters in hyperthyroid rats.

Adenosine acting on A(1) receptors has been related with neuroprotective and neuromodulatory actions, protection against oxidative stress and decrease of anxiety and nociceptive signaling. Previous studies demonstrated an inhibition of the enzymes that hydrolyze ATP to adenosine in the rat central nervous system after hyperthyroidism induction. Manifestations of hyperthyroidism include increased anxiety, nervousness, high O(2) consumption and physical hyperactivity. Here, we investigated the effects of administration of a specific agonist of adenosine A(1) receptor (N(6)-cyclopentyladenosine; CPA) on nociception, anxiety, exploratory response, locomotion and brain oxidative stress of hyperthyroid rats. Hyperthyroidism was induced by daily intraperitoneal injections of l-thyroxine (T4) for 14 days. Nociception was assessed with a tail-flick apparatus and exploratory behavior, locomotion and anxiety were analyzed by open-field and plus-maze tests. We verified the total antioxidant reactivity (TAR), lipid peroxide levels by the thiobarbituric acid reactive species (TBARS) reaction and the free radicals content by the DCF test. Our results demonstrated that CPA reverted the hyperalgesia induced by hyperthyroidism and decreased the exploratory behavior, locomotion and anxiety in hyperthyroid rats. Furthermore, CPA decreased lipid peroxidation in hippocampus and cerebral cortex of control rats and in cerebral cortex of hyperthyroid rats. CPA also increased the total antioxidant reactivity in hippocampus and cerebral cortex of control and hyperthyroid rats, but the production of free radicals verified by the DCF test was changed only in cerebral cortex. These results suggest that some of the hyperthyroidism effects are subjected to regulation by adenosine A(1) receptor, demonstrating the involvement of the adenosinergic system in this pathology.

Adenosine↗

PubMed2005

Aging affects oxidative state in hippocampus, hypothalamus and adrenal glands of Wistar rats.

The aging process is associated with cognitive impairment and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as well as with oxidative stress. We determined some parameters of oxidative stress in homogenates of hippocampus, hypothalamus and adrenal glands from male 2-, 6- and 24-months-old Wistar rats. A significant age-dependent increase in the generation of free radicals was observed in hippocampus, hypothalamus and adrenal glands, as well as on lipid peroxidation in hippocampus and hypothalamus. The glutathione peroxidase (GPx) activity was significantly reduced in hypothalamus and hippocampus from 6-months-old rats; a decline on GPx and catalase activities in adrenal glands of 24-months-old animals was also present. Interestingly, a great decrease in total antioxidant capacity was found in all tissues tested. Reported findings support the idea that oxidative events participate on multiple neuroendocrine-metabolic impairments and suggest that the oxidative stress found in hippocampus, hypothalamus and adrenals might be associated with age-related physiological deficits.

Adrenal Glands↗

PubMed2005

Repeated stress effects on nociception and on ectonucleotidase activities in spinal cord synaptosomes of female rats.

It has been reported that animals submitted to repeated restraint stress present various adaptation responses which are dependent on the sex. These adaptations include changes in nociception and adenine nucleotide hydrolysis. In this study, we report the effect of chronic administration of a gonadal steroid (17beta-estradiol) on ATP, ADP and AMP hydrolysis in spinal cord synaptosomes of adult ovariectomized (OVX) Wistar rats submitted to repeated restraint stress over 40 days. We also measured nociceptive threshold in these animals using the tail-flick test. The results show that tail-flick latencies were decreased in both stressed groups, OVX and OVX rats receiving estradiol replacement therapy, indicating reduced nociceptive threshold after exposure to repeated stress. Repeated restraint stress caused no effect on ATPase or ADPase activities. On the other hand, AMP hydrolysis in spinal cord synaptosomes from repeatedly stressed rats was decreased in OVX rats compared to non-stressed OVX ones, indicating reduced extracellular adenosine production; this effect was reversed by hormonal replacement. These observations suggest that nociceptive sensitivity to noxious stimuli is affected by repeated stress and that modulation of neurotransmission by adenine nucleotides in spinal cord may be altered by the interaction of sexual hormones and psychological factors, such as exposure to stress.

Adenosine Diphosphate↗

PubMed2005

Acute and repeated restraint stress influences cellular damage in rat hippocampal slices exposed to oxygen and glucose deprivation.

Several studies have shown that high corticosteroid hormone levels increase neuronal vulnerability. Here we evaluate the consequences of in vivo acute or repeated restraint stress on cellular viability in rat hippocampal slices suffering an in vitro model of ischemia. Cellular injury was quantified by measuring lactate dehydrogenase (LDH) and neuron-specific enolase released into the medium. Acute stress did not affect cellular death when oxygen and glucose deprivation (OGD) was applied both immediately or 24h after restraint. The exposure to OGD, followed by reoxygenation, resulted in increased LDH in the medium. Repeated stress potentiated the effect of OGD both, on LDH and neuron-specific enolase released to the medium. There was no effect of repeated stress on the release of S100B, an astrocytic protein. Additionally, no effect of repeated stress was observed on glutamate uptake by the tissue. These results suggest that repeated stress increases the vulnerability of hippocampal cells to an in vitro model of ischemia, potentiating cellular damage, and that the cells damaged by the exposure to repeated stress+OGD are mostly neurons. The uptake of glutamate was not observed to participate in the mechanisms responsible for rendering the neurons more susceptible to ischemic damage after repeated stress.

Analysis of Variance↗

PubMed2005

Nociception and locomotor activity are increased in ketogenic diet fed rats.

Ketogenic diets have been used to treat epilepsy in children for almost 80 years. However, there are only few studies concerning behavioral effects of these diets, besides their efficacy in treating seizure disorders induced by kainic acid or pentylenetetrazol in rats. Here, rats were fed with a ketogenic diet and locomotion, anxiety and nociception were investigated after 10 weeks. Male Wistar rats were weight matched and divided into two groups: control rats, that received regular laboratory ration, and KD rats, that received ketogenic diet (70% fat, 24% protein and no carbohydrate). Behavioral tests were applied after 10-12 weeks of treatment, and included tests to evaluate exploration (habituation to the open field), anxiety (plus-maze), and nociception (tail-flick measurement). Performance of the animals in the open field revealed a significant difference in the number of crossings, suggesting a higher locomotor activity in animals fed with a ketogenic diet. No differences in anxiety were observed, as evaluated by the plus-maze test. Nociception was measured by the latency in the tail-flick test, and ketogenic rats presented a hypernociceptive response. Yet, these animals responded to a stressor with the classic analgesia, similarly to the controls. The response of ketogenic diet fed rats to the stressor, however, was more prolonged. Exposure to a ketogenic diet may induce higher locomotor activity, together with a hypernociceptive state in the animals, possibly as a result of some alteration in the neural systems involved in the modulation of these behaviors.

Animals↗

PubMed2005

Repeated restraint stress reduces opioid receptor binding in different rat CNS structures.

Different effects of exposure to acute or to repeated stress have been observed upon the nociceptive response in rats. In the present study, we repeatedly submitted Wistar rats to restraint for 40 days, a treatment known to induce an increase in the nociceptive response in the tail-flick test. Afterwards, the effect of repeated restraint stress on the density of opioid receptors in rat spinal cord, frontal cortex, and hippocampus was investigated. Results showed that repeatedly stressed rats displayed a significant decrease in opioid receptors density in all structures studied; cortex (141.3 +/- 5.7 for control and 103.3 +/- 15.9 for stressed rats), hippocampus (92.4 +/- 7.2 for control and 64.8 +/- 7.7 for stressed rats), and spinal cord (122.2 +/- 12.8 for control and 79.7 +/- 9.7 for stressed rats). These findings suggest opioid mediation of the altered responses observed in these repeatedly-stressed animals, although the participation of non-opioid mechanisms in this phenomenon cannot be ruled out.

Animals↗

PubMed2005

Repeated restraint stress induces oxidative damage in rat hippocampus.

It has been shown that emotional stress may induce oxidative damage, and considerably change the balance between pro-oxidant and antioxidant factors in the brain. The aim of this study was to verify the effect of repeated restraint stress (RRS; 1 h/day during 40 days) on several parameters of oxidative stress in the hippocampus of adult Wistar rats. We evaluated the lipid peroxide levels (assessed by TBARS levels), the production of free radicals (evaluated by the DCF test), the total radical-trapping potential (TRAP) and the total antioxidant reactivity (TAR) levels, and antioxidant enzyme activities (SOD, GPx and CAT) in hippocampus of rats. The results showed that RRS induced an increase in TBARS levels and in GPx activity, while TAR was reduced. We concluded that RRS induces oxidative stress in the rat hippocampus, and that these alterations may contribute to the deleterious effects observed after prolonged stress.

Animals↗

PubMed2005

Neuroprotection and protein damage prevention by estradiol replacement in rat hippocampal slices exposed to oxygen-glucose deprivation.

Here we investigated the effects of estradiol replacement in ovariectomized female rats using hippocampal slices exposed to oxygen-glucose deprivation (OGD). OGD induced lactate dehydrogenase (LDH) release to the incubation medium, what was assumed as a parameter of cellular death. In the estradiol-treated group the LDH release was markedly decreased by 23% as compared to the vehicle-treated group. In attempt to study a possible mechanism by which estradiol acts, we investigated some parameters of oxidative stress. In both vehicle-treated and estradiol-treated groups, OGD significantly increased the free radical production by 34% and 16%, respectively, although no significant differences on total antioxidant capacity were observed. Interestingly, estradiol replacement prevented the significant reduction in tryptophan and tyrosine contents caused by OGD observed in vehicle-treated animals. Our results show that estradiol replacement in ovariectomized female rats decreases cellular susceptibility to an ischemic-like injury and suggest a role for the hormone on protein damage prevention.

Animals↗

PubMed2005

Nociceptive response and adenine nucleotide hydrolysis in synaptosomes isolated from spinal cord of hypothyroid rats.

Purinergic system exerts a significant influence on the modulation of pain pathways at the spinal site. Adenosine has antinociceptive properties in experimental and clinical situations, while ATP exerts pronociceptive actions in different pain models. In this study we investigated the hydrolysis of ATP to adenosine in synaptosomes from spinal cord in parallel with the nociceptive response of rats at different ages after hypothyroidism induction. Hypothyroidism elicited a significant increase in AMP hydrolysis to adenosine in synaptosomes from spinal cord of rats subjected to neonatal hypothyroidism and in 420-day-old rats submitted to thyroidectomy. Accordingly, these rats presented an analgesic response as a consequence of hypothyroidism. In contrast, the ATP hydrolysis was decreased in the spinal cord of 60-day-old hypothyroid rats in parallel with a significant increase in nociceptive response. These results indicate the involvement of adenine nucleotides in the control of the hypothyroidism-induced nociceptive response during development.

Adenine Nucleotides↗

PubMed2005

Hyperthyroidism changes nociceptive response and ecto-nucleotidase activities in synaptosomes from spinal cord of rats in different phases of development.

Changes in transport, receptors and production of extracellular adenosine have been observed after induction of hyperthyroidism. Adenosine is associated with inhibitory actions such as reduction in release of excitatory neurotransmitters and antinociception at spinal site. In contrast, ATP acts as an excitatory neurotransmitter and produces pronociceptive actions. ATP may be completely hydrolyzed to adenosine by an enzyme chain constituted by an ATP diphosphohydrolase and an ecto-5'-nucleotidase, as previously described in the spinal cord. Thus, we now investigated the effects of the hyperthyroidism on adenine nucleotide hydrolysis in the spinal cord and verified the nociceptive response in this pathology during different phases of development. Hyperthyroidism was induced in male Wistar rats, aged 5, 60 and 330 days by daily intraperitoneal injections of L-thyroxine (T4) for 14 days. Nociception was assessed with a tail-flick apparatus. Rats starting the treatment aged 5 days demonstrated a significant increase in ADP and AMP hydrolysis and increased tail-flick latency (TFL). In contrast, in the spinal cord from hyperthyroid rats aged 60 and 330 days old, the hydrolysis of ATP, ADP and AMP were significantly decreased. Accordingly, the tail-flick latency was decreased, indicating a hyperalgesic response. These results suggest the involvement of ecto-nucleotidases in the control of the hyperthyroidism-induced nociceptive response in rats at distinct developmental stages.

Adenosine Triphosphatases↗

PubMed2005

Na+,K(+)-ATPase activity is reduced in hippocampus of rats submitted to an experimental model of depression: effect of chronic lithium treatment and possible involvement in learning deficits.

This study was undertaken to verify the effects of chronic stress and lithium treatments on the hippocampal Na+,K(+)-ATPase activity of rats, as well as to investigate the effects of stress interruption and post-stress lithium treatment on this enzyme activity and on spatial memory. Two experiments were carried out; in the first experiment, adult male Wistar rats were divided into two groups: control and submitted to a chronic variate stress paradigm, and subdivided into treated or not with LiCl. After 40 days of treatment, rats were killed, and Na+,K(+)-ATPase activity was determined. In the second experiment, rats were stressed during 40 days, and their performance was evaluated in the Water Maze task. The stressed group was then subdivided into four groups, with continued or interrupted stress treatment and treated or not with lithium for 30 additional days. After a second evaluation of performance in the Water Maze, rats were killed and Na+,K(+)-ATPase activity was also measured. Results showed an impairment in Na+,K(+)-ATPase activity and in Water Maze performance of chronically stressed rats, which were prevented by lithium treatment and reversed by lithium treatment and by stress interruption. These results suggest that the modulation of Na+,K(+)-ATPase activity may be one of the mechanisms of action of lithium in the treatment of mood disorders.

Analysis of Variance↗

PubMed2004

Changes in S100B cerebrospinal fluid levels of rats subjected to predator stress.

Predator stress is a type of psychogenic stress induced by an innate recognition of threat. S100B, a calcium-binding protein secreted by astrocytes, has been associated with neurotrophic or neurotoxic action in several neuropsychiatric disorders. It has been recently demonstrated that serum S100B levels in rats are increased after stress by immobilization [S. Scaccianoce, P. Del Bianco, G. Pannitteri, F. Passarelli, Relationship between stress and circulating levels of S100B protein, Brain Res. 1004 (2004) 208-11]. This study aimed to measure cerebrospinal fluid (CSF) S100B in rats after an acute stress situation, which is induced by exposure to a predator. S100B was measured in CSF and in hippocampal and cortical slices by ELISA. Forty-three male Wistar rats, aged 70 days, were randomly assigned to handled (control) or stressed groups (exposed to a cat for 5 min). CSF and brain tissue were removed 1 or 24 h after the procedures. Rats exposed to the cat demonstrated a biphasic change in CSF S100B levels. An increase was observed at 1 h after cat exposure, and a decrease was observed 24 h later, although this was not accompanied by changes in S100B content in hippocampus or cerebral cortex. The effectiveness of the stressor used was confirmed by increased freezing response (during cat exposure) and increased anxiety in the plus maze test (1 h after cat exposure). These results indicate that CSF S100B is changed by stress, reinforcing the possibility that this protein is involved in the adaptive response to stress and/or in secondary neuropsychiatric disorders.

Analysis of Variance↗

PubMed2004

Cerebrospinal fluid S100B increases reversibly in neonates of methyl mercury-intoxicated pregnant rats.

Methylmercury (MeHg), an organic methylated form of mercury, is one of the most hazardous environmental pollutants. MeHg is a potent neurotoxin, particularly during brain development. Neurotoxicity-induced by MeHg in prenatal age can cause mental disorders, cerebral palsy and seizures. We investigated cerebrospinal fluid (CSF) and brain tissue contents of S100B, a calcium binding protein produced and secreted by astrocytes, which has trophic and toxic activity on neurons depending on concentration. Pregnant rats were exposed to MeHg (5 mg/kg per day, on the 12th, 13th and 14th days of pregnancy). CSF and brain tissue (hippocampus, cerebral cortex and cerebellum) were obtained from neonate rats on 1, 15 and 30 days postnatal. MeHg accumulation was measured in brain tissue after birth and on the 30th postnatal day. An increase of CSF S100B was observed on the 15th, but not on the 30th postnatal day. Hippocampal tissue demonstrated increased S100B (and reduction in glial fibrillary acidic protein) immediately after birth, but not later. No changes in the S100B content were observed in cerebellum and cerebral cortex. No changes were observed in the spatial learning of these rats at adult age. These specific and reversible changes in the hippocampus could be related to the cognitive and epileptic disorders attributed to MeHg. Our results further indicate the glial involvement in the MeHg-induced neurotoxicity. The increment of CSF S100B in neonates exposed to MeHg reinforces the view that increased S100B is related to damage in the nervous system and that S100B could be a marker for MeHg-neurotoxicity. Although the cellular mechanism related to MeHg-induced increase in S100B content in CSF remains unknown, our results suggest the use of S100B as a peripheral marker of brain damage induced by MeHg.

Animals↗

PubMed2004

Protective effect of pregnanolone against lipoperoxidation and free radicals generation induced in hypothalamus of ovariectomized rats submitted to CO2 exposure.

Several studies support an association between gonadal hormones and oxidative state. This study aimed to determine the consequence of the absence of ovarian hormones on the oxidative status of animals submitted to acute stress induced by CO(2) inhalation. We also evaluated the effect of pregnanolone administration upon the oxidative status in distinct brain structures of ovariectomized (OVX) rats exposed to CO(2). Female rats were divided into intact and OVX and exposed or unexposed to CO(2). Oxidative status was evaluated by 2',7'-dichlorofluorescein (DCF) assay, assessment of malondialdehyde (MDA), as an indicator of lipoperoxidation (through the thiobarbituric acid-reactive substances assay, TBARS), and the total antioxidant reactivity (TAR). Both DCF and TBARS were increased in the hypothalamus of animals submitted to OVX and stress. Nevertheless, free radical production and MDA levels were not affected in either condition alone. In the cerebral cortex, lower MDA levels were observed in OVX animals. Pregnanolone administered to rats submitted to CO(2)+OVX resulted in reduced MDA levels and free radicals production in hypothalamus. We suggest that ovarian hormones may protect the hypothalamus against oxidative stress, particularly when the animals are submitted to challenges. Pregnanolone may protect, at least in part, the hypothalamus of OVX rats from oxidative stress.

Animals↗

PubMed2004

Acute and chronic stress alter ecto-nucleotidase activities in synaptosomes from the rat hippocampus.

Hyperactivity of the stress response has long been recognized as maladaptive. The hippocampus, a brain structure important in mediating this response, is known to be affected by chronic stress, a situation reported to induce changes in adenine nucleotide hydrolysis in the rat. The enzymes catalyzing the hydrolysis of ATP to adenosine in the synaptic cleft are thought to have a role in modulating and controlling synaptic transmission. This study aimed to investigate the effect of acute and repeated restraint stress on the ATP, ADP and AMP hydrolyses in rat hippocampal synaptosomes. Adult male Wistar rats were submitted to acute or repeated (15 and 40 days) stress, and ATPase-ADPase, and 5'nucleotidase activities were assayed in the hippocampal synaptosomal fraction. Acute stress induced increased hydrolyses of ATP (21%), ADP (21%) and AMP (40%). In contrast, ATP hydrolysis was increased by 20% in repeatedly stressed rats, without changes in the ADP or AMP hydrolysis. The same results were observed after 15 or 40 days of stress. Therefore, acute stress increases ATP diphosphohydrolase activity which, in association with 5'-nucleotidase, contributes to the elimination of ATP and provides extracellular adenosine. Interestingly, increased ecto-ATPase activity in response to chronic stress reveals an adaptation to this treatment.

Acute Disease↗