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Hypoxia in preterm infants is a clinical condition that has been associated with cognitive and behavioral disturbances for which treatment strategies are strongly required. Melatonin administration following brain insults has been considered a promising therapeutic strategy due to its antioxidant and anti-inflammatory effects. Not surprisingly, it has been extensively studied for preventing disturbances following brain injury. This study evaluated the effects of melatonin on developmental disturbances, memory disruption, and hippocampal cell loss induced by neonatal anoxia in rats. Neonatal Wistar rats were subjected to anoxia and subsequently treated with melatonin. Later, maturation of physical characteristics, ontogeny of reflexes, learning and memory in the Morris water maze (MWM), and estimates of the number of hippocampal neurons, were evaluated. Melatonin treatment attenuated (1) female anoxia-induced delay in superior incisor eruption, (2) female anoxia-induced vibrissae placement reflexes, and (3) male and female anoxia-induced hippocampal neuronal loss. Melatonin also promoted an increase (5) in swimming speeds in the MWM. In addition, PCA analysis showed positive associations between the acoustic startle, auditory canal open, and free fall righting parameters and negative associations between the male vehicle anoxia group and the male melatonin anoxia group. Therefore, melatonin treatment attenuates both anoxia-induced developmental deficits and hippocampal neuronal loss.
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Neonatal oxygen deficiency in rats may disturb growth and long-term metabolic homeostasis. In order to facilitate metabolic evaluation, the subjects are usually housed individually. However, social isolation associated with individually housed conditions alters animal behavior, which may influence the experimental results. This study investigated the effects of social isolation on neonatal anoxia-induced changes in growth and energy metabolism. Male and female Wistar rats were exposed, on postnatal day 2 (P2), to either 25-min of anoxia or control treatment. From P27 onward, part of the subjects of each group was isolated in standard cages, and the remaining subjects were housed in groups. At P34 or P95, the subjects were fasted for 18 h, refeed for 1 h, and then perfused 30 min later. Glycemia, leptin, insulin, and morphology of the pancreas were evaluated at both ages. For subjects perfused at P95, body weight and food intake were recorded up to P90, and the brain was collected for Fos and NeuN immunohistochemistry. Results showed that male rats exposed to neonatal anoxia and social isolation exhibited increased body weight gain despite the lack of changes in food intake. In addition, social isolation (1) decreased post-fasting weight loss and post-fasting food intake and (2) increased glycemia, insulin, and leptin levels of male and female rats exposed to anoxia and control treatments, both at P35 and P95. Furthermore, although at P35, anoxia increased insulin levels of males, it decreased the area of the ß-positive cells in the pancreas of females. At P95, anoxia increased post-prandial weight loss of males, post-fasting food intake, insulin, and leptin, and decreased Fos expression in the arcuate nucleus (ARC) of males and females. Hyperphagia was associated with possible resistance to leptin and insulin, suspected by the high circulating levels of these hormones and poor neuronal activation of ARC. This study demonstrated that continuous social isolation from weaning modifies, in a differentiated way, the long-term energy metabolism and growth of male and female Wistar rats exposed to neonatal anoxia or even control treatments. Therefore, social isolation should be considered as a factor that negatively influences experimental results and the outcomes of the neonatal injury. These results should also be taken into account in clinical procedures, since the used model simulates the preterm babies' conditions and some therapeutic approaches require isolation.
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Animais Recém-Nascidos , Peso Corporal , Ingestão de Alimentos , Metabolismo Energético , Hipóxia , Ratos Wistar , Isolamento Social , Animais , Isolamento Social/psicologia , Masculino , Feminino , Ratos , Metabolismo Energético/fisiologia , Ingestão de Alimentos/fisiologia , Hipóxia/metabolismo , Peso Corporal/fisiologia , Leptina/sangue , Leptina/metabolismo , Glicemia/metabolismo , Insulina/sangue , Insulina/metabolismo , Desmame , Fatores EtáriosRESUMO
Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most important reasons for morbidity and mortality in term-born infants. HIE impacts early somatic, neurological, and motor development including social. To illustrate the damages in the sensorimotor system, an adapted and validated model of neonatal anoxia is used. This study evaluated the sex differences in Wistar rats, neurological reflex, and motor development at the suckling period. Short- and long-term impairments associated with sex differences were observed. In general, anoxic males were more affected in comparison to their control group and to anoxic females. Long-lasting effects of the injury in adolescent rats predominately affected males. Similar to previous studies, we also found a decrease in the number of the substantia nigra cells in both sexes, compared to their control. So far, the results indicate that HIE caused neurobehavioral alterations and asymmetrical motor behavior with brain damage, possibly related to cognitive impairments previously observed at adolescence. These alterations may represent a useful endpoint for studying the efficacy of potential strategies that may improve the developmental consequences of a perinatal asphyxia insult in humans.
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Hipóxia-Isquemia Encefálica , Humanos , Lactente , Gravidez , Animais , Ratos , Feminino , Masculino , Ratos Wistar , Animais Recém-Nascidos , Modelos Animais de Doenças , HipóxiaRESUMO
Therapeutic hypothermia (TH) is well established as a standard treatment for term and near-term infants. However, therapeutic effects of hypothermia following neonatal anoxia in very premature babies remains inconclusive. The present rodent model of preterm neonatal anoxia has been shown to alter developmental milestones and hippocampal neurogenesis, and to disrupt spatial learning and memory in adulthood. These effects seem to be reduced by post-insult hypothermia. Epigenetic-related mechanisms have been postulated as valuable tools for developing new therapies. Dentate gyrus neurogenesis is regulated by epigenetic factors. This study evaluated whether TH effects in a rodent model of preterm oxygen deprivation are based on epigenetic alterations. The effects of TH on both developmental features (somatic growth, maturation of physical characteristics and early neurological reflexes) and performance of behavioral tasks at adulthood (spatial reference and working memory, and fear conditioning) were investigated in association with the possible involvement of the epigenetic operator Enhancer of zeste homolog 2 (Ezh2), possibly related to long-lasting effects on hippocampal neurogenesis. Results showed that TH reduced both anoxia-induced hippocampal neurodegeneration and anoxia-induced impairments on risk assessment behavior, acquisition of spatial memory, and extinction of auditory and contextual fear conditioning. In contrast, TH did not prevent developmental alterations caused by neonatal anoxia and did not restore hippocampal neurogenesis or cause changes in EZH2 levels. In conclusion, despite the beneficial effects of TH in hippocampal neurodegeneration and in reversing disruption of performance of behavioral tasks following oxygen deprivation in prematurity, these effects seem not related to developmental alterations and hippocampal neurogenesis and, apparently, is not caused by Ezh2-mediated epigenetic alteration.
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Hipocampo/crescimento & desenvolvimento , Hipotermia Induzida/métodos , Hipóxia Encefálica/fisiopatologia , Hipóxia Encefálica/terapia , Memória Espacial/fisiologia , Animais , Animais Recém-Nascidos , Feminino , Hipóxia Encefálica/psicologia , Lactação/fisiologia , Masculino , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function. Intracerebroventricular injection of streptozotocin (icv-STZ) has been used as an experimental model of Sporadic AD (SAD) in rodents and represents a promising tool for etiopathogenic analysis and evaluation of new therapeutic proposals for AD. The icv-STZ model shows many aspects of SAD abnormalities, resulting in decreased brain glucose and energy metabolism, cognitive impairment, oxidative stress, neuronal loss, and amyloid angiopathy. Royal jelly (RJ), a substance produced by worker honeybees of the Apis mellifera species, has been popularly used for more than 30 years in areas related to health eating and natural medicine. Researches indicate that RJ has a several pharmacological activities, including neuroprotective and improvement of cognitive function. The objective of this study was to investigate the effects of oral treatment with royal jelly during 2 weeks in Wistar rats submitted to icv-STZ on a working memory and neuroprotection, as evaluated by neurogenesis, neurodegeneration and oxidative stress. In this study, icv-STZ injection induced deleterious effects in the hippocampus, associated with cognitive impairments, and developed marked neurodegeneration, besides the reduction of neurogenesis and increased oxidative stress. On the other hand, RJ long-term oral administration induced beneficial effects in animals injured by icv-STZ injection, increasing retention time for working spatial memory, reducing neurodegeneration and oxidative stress level and increasing the proliferation of new neurons in the hippocampus. Thus, RJ promotes beneficial effects on cognitive functions and exhibits a neuroprotective action in the STZ experimental model of SAD.
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function. Intracerebroventricular injection of streptozotocin (icv-STZ) has been used as an experimental model of Sporadic AD (SAD) in rodents and represents a promising tool for etiopathogenic analysis and evaluation of new therapeutic proposals for AD. The icv-STZ model shows many aspects of SAD abnormalities, resulting in decreased brain glucose and energy metabolism, cognitive impairment, oxidative stress, neuronal loss, and amyloid angiopathy. Royal jelly (RJ), a substance produced by worker honeybees of the Apis mellifera species, has been popularly used for more than 30 years in areas related to health eating and natural medicine. Researches indicate that RJ has a several pharmacological activities, including neuroprotective and improvement of cognitive function. The objective of this study was to investigate the effects of oral treatment with royal jelly during 2 weeks in Wistar rats submitted to icv-STZ on a working memory and neuroprotection, as evaluated by neurogenesis, neurodegeneration and oxidative stress. In this study, icv-STZ injection induced deleterious effects in the hippocampus, associated with cognitive impairments, and developed marked neurodegeneration, besides the reduction of neurogenesis and increased oxidative stress. On the other hand, RJ long-term oral administration induced beneficial effects in animals injured by icv-STZ injection, increasing retention time for working spatial memory, reducing neurodegeneration and oxidative stress level and increasing the proliferation of new neurons in the hippocampus. Thus, RJ promotes beneficial effects on cognitive functions and exhibits a neuroprotective action in the STZ experimental model of SAD.
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function. Intracerebroventricular injection of streptozotocin (icv-STZ) has been used as an experimental model of Sporadic AD (SAD) in rodents and represents a promising tool for etiopathogenic analysis and evaluation of new therapeutic proposals for AD. The icv-STZ model shows many aspects of SAD abnormalities, resulting in decreased brain glucose and energy metabolism, cognitive impairment, oxidative stress, neuronal loss, and amyloid angiopathy. Royal jelly (RJ), a substance produced by worker honeybees of the Apis mellifera species, has been popularly used for more than 30 years in areas related to health eating and natural medicine. Researches indicate that RJ has a several pharmacological activities, including neuroprotective and improvement of cognitive function. The objective of this study was to investigate the effects of oral treatment with royal jelly during 2 weeks in Wistar rats submitted to icv-STZ on a working memory and neuroprotection, as evaluated by neurogenesis, neurodegeneration and oxidative stress. In this study, icv-STZ injection induced deleterious effects in the hippocampus, associated with cognitive impairments, and developed marked neurodegeneration, besides the reduction of neurogenesis and increased oxidative stress. On the other hand, RJ long-term oral administration induced beneficial effects in animals injured by icv-STZ injection, increasing retention time for working spatial memory, reducing neurodegeneration and oxidative stress level and increasing the proliferation of new neurons in the hippocampus. Thus, RJ promotes beneficial effects on cognitive functions and exhibits a neuroprotective action in the STZ experimental model of SAD.
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BACKGROUND: Neonatal anoxia may cause neurological injuries, behavioral alterations and changes in somatic growth. Somatic developmental changes suggest a possible effect of anoxia on energy metabolism and/or feeding behavior. Short-term effects of oxygen deficit on energy homeostasis have been described. In contrast, just a few studies report long-term effects. This study investigated the effects of neonatal anoxia on energy metabolism and somatic development at adulthood of males and females Wistar rats. METHOD: Male (m) and female (f) rats were exposed, on postnatal day 2 (P2), to either 25-min of Anoxia or Control treatment. At P34 part of the subjects of each group was fasted for 18 h, refeed for 1 h and then perfused 30 min later, at P35; the remaining subjects were submitted to these treatments at P94 and perfused at P95. Therefore, there were 8 groups: AmP35, AmP95, AfP35, AfP95, CmP35, CmP95, CfP35 and CfP95. For subjects perfused at P95, body weight and food intake were recorded up to P90. For subjects perfused at P35 and P95, glycemia, leptin and insulin were assessed after fasting and refeed. After perfusion the encephalon and pancreas were collected for Fos immunohistochemistry and Hematoxylin-Eosin stain analyses. RESULTS: Even though neonatal anoxia did not interfere with regular food intake, it reduced body weight gain along growing in both male and female subjects as compared to the corresponding controls. At P35 neonatal anoxia decreased post-prandial glycemia and increased insulin. While at P95 neonatal anoxia altered the pancreatic histomorphology and increased post-fasting weight loss, decreasing leptin, insulin and glycemia secretion, as well Fos immunoreactivity (IR) in ARC. CONCLUSION: Neonatal anoxia impairs long-term energy metabolism and somatic development in Wistar rats, with differences related to sex and age.
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Metabolismo Energético/fisiologia , Jejum/metabolismo , Hipóxia/metabolismo , Aumento de Peso/fisiologia , Animais , Animais Recém-Nascidos , Glicemia , Feminino , Insulina/sangue , Leptina/sangue , Masculino , Ratos , Ratos WistarRESUMO
Neonatal anoxia induces long-term brain injury that may underlie neurobehavioral deficits at adolescence. Neonatal anoxia, induced by exposure of 30-hour old pups to 100% nitrogen, represents a non-invasive and global stimulus, which simulates clinical conditions of human pre-term babies (around 6 gestational months). Previous studies showed that neonatal anoxia induced impairments of spatial memory and altered anxiety-like behaviors in male rats tested at adult age. This study evaluated if neonatal anoxia induces similar behavioral effects in female rats, as compared to males, by testing the animals at adolescence, and also searched for possible cell losses in hippocampal subfields. Results in the Elevated Plus Maze test showed that anoxic females spent proportionally more time within the open arms as compared to anoxic males, suggesting a less anxious-like behavior. In the Morris Water Maze Test, latencies and path lengths of the anoxic subjects were longer as compared to control subjects, thus indicating that anoxia disrupted the cognitive functions required for spatial mapping. In addition, results showed that anoxia-induced disruption was greater in male rats as compared to female rats. Stereological analysis revealed that anoxic male rats exhibited significant cell losses in the dorsal hippocampus dentate gyrus and CA1 subfields, but not in CA3-2 subfield. Similar results were observed in the ventral hippocampus, but now with cell loss in the male CA3-2 subfield. There were also significant cell loss differences of anoxic male rats as compared to anoxic female rats. In conclusion, neonatal anoxia induces deleterious and long lasting behavioral and cognitive disruptions, and these effects were stronger in male rats as compared to female rats. These changes are congruent with the pattern of cell losses observed in hippocampal subfields. Together, these results emphasize the relevance of scientific research, aiming at clinical strategies and treatments, consider the sex differential patterns of response to neonatal injury.
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Comportamento Animal/fisiologia , Morte Celular/fisiologia , Hipocampo/patologia , Hipóxia Encefálica/psicologia , Aprendizagem em Labirinto/fisiologia , Animais , Feminino , Hipóxia Encefálica/patologia , Masculino , Ratos , Fatores Sexuais , Memória Espacial/fisiologiaRESUMO
Previous research shows Ouabain (OUA) to bind Na, K-ATPase, thereby triggering a number of signaling pathways, including the transcription factors NFá´B and CREB. These transcription factors play a key role in the regulation of BDNF and WNT-ß-catenin signaling cascades, which are involved in neuroprotection and memory regulation. This study investigated the effects of OUA (10â¯nM) in the modulation of the principal signaling pathways involved in morphological plasticity and memory formation in the hippocampus of adult rats. The results show intrahippocampal injection of OUA 10â¯nM to activate the Wnt/ß-Catenin signaling pathway and to increase CREB/BDNF and NFá´B levels. These effects contribute to important changes in the cellular microenvironment, resulting in enhanced levels of dendritic branching in hippocampal neurons, in association with an improvement in spatial reference memory and the inhibition of long-term memory extinction.
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Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Ouabaína/farmacologia , Memória Espacial/efeitos dos fármacos , Animais , Proteína Axina/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Hipocampo/fisiologia , Masculino , Aprendizagem em Labirinto , Microinjeções , NF-kappa B/metabolismo , Proteínas de Neoplasias/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Ratos , Memória Espacial/fisiologia , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismoRESUMO
Maternal melatonin provides photoperiodic information to the fetus and thus influences the regulation and timing of the offspring's internal rhythms and preparation for extra-uterine development. There is clinical evidence that melatonin deprivation of both mother and fetus during pregnancy, and of the neonate during lactation, results in negative long-term health outcomes. As a consequence, we hypothesized that the absence of maternal pineal melatonin might determine abnormal brain programming in the offspring, which would lead to long-lasting implications for behavior and brain function. To test our hypothesis, we investigated in rats the effects of maternal melatonin deprivation during gestation and lactation (MMD) to the offspring and the effects of its therapeutic replacement. The parameters evaluated were: (1) somatic, physical growth and neurobehavioral development of pups of both sexes; (2) hippocampal-dependent spatial learning and memory of the male offspring; (3) adult hippocampal neurogenesis of the male offspring. Our findings show that MMD significantly delayed male offspring's onset of fur development, pinna detachment, eyes opening, eruption of superior incisor teeth, testis descent and the time of maturation of palmar grasp, righting reflex, free-fall righting and walking. Conversely, female offspring neurodevelopment was not affected. Later on, male offspring show that MMD was able to disrupt both spatial reference and working memory in the Morris Water Maze paradigm and these deficits correlate with changes in the number of proliferative cells in the hippocampus. Importantly, all the observed impairments were reversed by maternal melatonin replacement therapy. In summary, we demonstrate that MMD delays the appearance of physical features, neurodevelopment and cognition in the male offspring, and points to putative public health implications for night shift working mothers.
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Ritmo Circadiano/fisiologia , Cognição/fisiologia , Lactação/fisiologia , Melatonina/metabolismo , Efeitos Tardios da Exposição Pré-Natal , Animais , Comportamento Animal/fisiologia , Feminino , Crescimento e Desenvolvimento/fisiologia , Masculino , Memória/fisiologia , Mães , Neurogênese/fisiologia , Fotoperíodo , Glândula Pineal/metabolismo , Glândula Pineal/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Ratos Wistar , Aprendizagem Espacial/fisiologiaRESUMO
Currently, one of the important causes of brain injury in new-borns is the neonatal anoxia which impacts the perinatology services worldwide. Animal models of anoxia have been used to assess its effects at cellular and behavioural levels in all ages, but few studies focus on sex differences. This study aimed to investigate some physical parameters of development, sensorimotor alterations, early neurological reflexes as well as the density of cells in motor and sensorimotor cerebral cortex of adolescent rats submitted to neonatal anoxia. The results presented significant differences in most of the evaluated parameters, such as body weight and lenght, medio-lateral head axis, eruption of superior incisor, palmar grasp, auditory startle, negative geotaxis, showing that neonatal anoxia affects physical parameters and neurological development, with sex differences. Cellular analysis revealed decreased amount of neurons in motor cortex and primary sensory hind limb and forelimb regions in anoxic group, along with gender difference, as compared to control groups. There is an important rationale for performing early assessment of sensorimotor deficits as there is similarity of the model with high risk human neonates and the sequelae in later life periods, which can be inferred from the present results with suggestion of a possible correlation between sensorimotor development delay and cellular changes in sensorimotor cortex. Furthermore, these observed sex dependent alterations certainly will address further studies and should be considered especially in treatments and strategies to avoid or minimize the neonatal anoxic effects.
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Força da Mão/fisiologia , Hipóxia/fisiopatologia , Atividade Motora/fisiologia , Reflexo/fisiologia , Córtex Sensório-Motor/patologia , Caracteres Sexuais , Estimulação Acústica , Animais , Animais Recém-Nascidos , Asfixia Neonatal , Aprendizagem da Esquiva/fisiologia , Peso Corporal/fisiologia , Morte Celular , Modelos Animais de Doenças , Feminino , Masculino , Ratos , Ratos Wistar , Vibrissas/inervaçãoRESUMO
Melanin-concentrating hormone (MCH) is a hypothalamic peptide that plays a critical role in the regulation of food intake and energy metabolism. In this study, we investigated the potential role of dense hippocampal MCH innervation in the spatially oriented food-seeking component of feeding behavior. Rats were trained for eight sessions to seek food buried in an arena using the working memory version of the food-seeking behavior (FSB) task. The testing day involved a bilateral anti-MCH injection into the hippocampal formation followed by two trials. The anti-MCH injection did not interfere with the performance during the first trial on the testing day, which was similar to the training trials. However, during the second testing trial, when no food was presented in the arena, the control subjects exhibited a dramatic increase in the latency to initiate digging. Treatment with an anti-MCH antibody did not interfere with either the food-seeking behavior or the spatial orientation of the subjects, but the increase in the latency to start digging observed in the control subjects was prevented. These results are discussed in terms of a potential MCH-mediated hippocampal role in the integration of the sensory information necessary for decision-making in the pre-ingestive component of feeding behavior.
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Comportamento Alimentar , Hipocampo/metabolismo , Hormônios Hipotalâmicos/metabolismo , Melaninas/metabolismo , Hormônios Hipofisários/metabolismo , Animais , Tomada de Decisões , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Exploratório , Hipocampo/efeitos dos fármacos , Hormônios Hipotalâmicos/antagonistas & inibidores , Hormônios Hipotalâmicos/imunologia , Soros Imunes/farmacologia , Masculino , Melaninas/antagonistas & inibidores , Melaninas/imunologia , Hormônios Hipofisários/antagonistas & inibidores , Hormônios Hipofisários/imunologia , Ratos WistarRESUMO
Neonates that suffer oxygen deprivation during birth can have long lasting cognitive deficits, such as memory and learning impairments. Hippocampus, one of the main structures that participate in memory and learning processes, is a plastic and dynamic structure that conserves during life span the property of generating new cells which can become neurons, the so-called neurogenesis. The present study investigated whether a model of rat neonatal anoxia, that causes only respiratory distress, is able to alter the hippocampal volume, the neurogenesis rate and has functional implications in adult life. MRI analysis revealed significant hippocampal volume decrease in adult rats who had experienced neonatal anoxia compared to control animals for rostral, caudal and total hippocampus. In addition, these animals also had 55.7% decrease of double-labelled cells to BrdU and NeuN, reflecting a decrease in neurogenesis rate. Finally, behavioral analysis indicated that neonatal anoxia resulted in disruption of spatial working memory, similar to human condition, accompanied by an anxiogenic effect. The observed behavioral alterations caused by oxygen deprivation at birth might represent an outcome of the decreased hippocampal neurogenesis and volume, evidenced by immunohistochemistry and MRI analysis. Therefore, based on current findings we propose this model as suitable to explore new therapeutic approaches.
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Ansiedade/etiologia , Comportamento Animal/fisiologia , Hipocampo/patologia , Hipóxia/complicações , Transtornos da Memória/etiologia , Memória de Curto Prazo/fisiologia , Neurogênese/fisiologia , Memória Espacial/fisiologia , Fatores Etários , Animais , Animais Recém-Nascidos , Ansiedade/fisiopatologia , Modelos Animais de Doenças , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/fisiopatologia , Ratos , Ratos WistarRESUMO
Physical exercise stimulates cell proliferation in the adult dentate gyrus and facilitates acquisition and/or retention of hippocampal-dependent tasks. It is established that regular physical exercise improves cognitive performance. However, it is unclear for how long these benefits last after its interruption. Independent groups of rats received both free access to either unlocked (EXE Treatment) or locked (No-EXE Treatment) running wheels for 7 days, and daily injections of bromodeoxyuridine (BrdU) in the last 3 days. After a time delay period of either 1, 3, or 6 weeks without training, the animals were tested in the Morris water maze (MWM) either in a working memory task dependent on hippocampal function (MWM-HD) or in a visible platform searching task, independent on hippocampal function (MWM-NH). Data confirmed that exposure of rats to 7 days of spontaneous wheel running increases cell proliferation and neurogenesis. In contrast, neurogenesis was not accompanied by significant improvements of performance in the working memory version of the MWM. Longer time delays between the end of exercise and the beginning of cognitive training in the MWM resulted in lower cell survival; that is, the number of novel surviving mature neurons was decreased when this delay was 6 weeks as compared with when it was 1 week. In addition, data showed that while exposure to the MWM-HD working memory task substantially increased survival of novel neurons, exposure to the MWM-NH task did not, thus indicating that survival of novel dentate gyrus neurons depends on the engagement of this brain region in performance of cognitive tasks. © 2015 Wiley Periodicals, Inc.
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Sobrevivência Celular/fisiologia , Cognição/fisiologia , Atividade Motora/fisiologia , Neurogênese/fisiologia , Neurônios/fisiologia , Aprendizagem Espacial/fisiologia , Análise de Variância , Animais , Antígenos Nucleares/metabolismo , Bromodesoxiuridina , Contagem de Células , Giro Denteado/citologia , Giro Denteado/fisiologia , Imuno-Histoquímica , Masculino , Memória de Curto Prazo/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/citologia , Distribuição Aleatória , Ratos Wistar , Memória Espacial/fisiologia , Percepção Visual/fisiologiaRESUMO
Exposure to environmental tobacco smoke (ETS) in the early postnatal period has been associated with several diseases; however, little is known about the brain effects of ETS exposure during this critical developmental period or the long-term consequences of this exposure. This study investigated the effects of the early postnatal ETS exposure on both reference and working memory, synaptic proteins and BDNF from late infancy to early adulthood (P3-P73). BALB/c mice were exposed to ETS generated from 3R4F reference research cigarettes (0.73 mg of nicotine/cigarette) from P3 to P14. Spatial reference and working memory were evaluated in the Morris water maze during infancy (P20-P29), adolescence (P37-P42) and adulthood (P67-P72). Synapsin, synaptophysin, PSD95 and brain-derived neurotrophic factor (BDNF) were assessed at P15, P35 and P65 by immunohistochemistry and immunoblotting. Mice that were exposed to ETS during the early postnatal period showed poorer performance in the spatial reference memory task. Specifically, the ETS-exposed mice exhibited a significantly reduced time and distance traveled in the target quadrant and in the platform location area than the controls at all ages evaluated. In the spatial working memory task, ETS disrupted the maintenance but not the acquisition of the critical spatial information in both infancy and adolescence. ETS also induced changes in synaptic components, including decreases in synapsin, synaptophysin, PSD95 and BDNF levels in the hippocampus. Exposure to ETS in the early postnatal period disrupts both spatial reference and working memory; these results may be related to changes in synaptogenesis in the hippocampus. Importantly, most of these effects were not reversed even after a long exposure-free period.
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Envelhecimento/patologia , Exposição Ambiental/efeitos adversos , Proteínas de Membrana/metabolismo , Fumar/efeitos adversos , Aprendizagem Espacial , Memória Espacial , Sinapses/metabolismo , Animais , Animais Recém-Nascidos , Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Monóxido de Carbono/análise , Feminino , Hipocampo/metabolismo , Immunoblotting , Imuno-Histoquímica , Masculino , Aprendizagem em Labirinto , Camundongos Endogâmicos BALB C , Análise e Desempenho de Tarefas , Fatores de TempoRESUMO
The basolateral amygdala complex (BLA), including the lateral (LA), basal (BA) and accessory basal (AB) nuclei, is involved in acquisition of contextual and auditory fear conditioning. The BA is one of the main targets for hippocampal information, a brain structure critical for contextual learning, which integrates several discrete stimuli into a single configural representation. Congruent with the hodology, selective neurotoxic damage to the BA results in impairments in contextual, but not auditory, fear conditioning, similarly to the behavioral impairments found after hippocampal damage. This study evaluated the effects of muscimol-induced reversible inactivation of the BA during a simultaneous contextual and auditory fear conditioning training on later fear responses to both the context and the tone, tested separately, without muscimol administration. As compared to control rats micro-infused with vehicle, subjects micro-infused with muscimol before training exhibited, during testing without muscimol, significant reduction of freezing responses to the conditioned context, but not to the conditioned tone. Therefore, reversible inactivation of the BA during training impaired contextual, but not auditory fear conditioning, thus confirming and extending similar behavioral observations following selective neurotoxic damage to the BA and, in addition, revealing that this effect is not related to the lack of a functional BA during testing.
Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiologia , Condicionamento Clássico/fisiologia , Medo/fisiologia , Animais , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Medo/efeitos dos fármacos , Ketamina/farmacologia , Masculino , Ratos , Ratos Wistar , Xilazina/farmacologiaRESUMO
AIM: To investigate tactile perception and manual dexterity, with or without visual feedback, in males with Duchenne muscular dystrophy (DMD). METHOD: Forty males with DMD (mean age 9 y 8 mo, SD 2 y 3 mo; range 5-14 y), recruited from the teaching hospital of the School of Medicine of the University of São Paulo, with disease severity graded as '1' to '6' on the Vignos Scale and '1' on Brooke's Scale, and 49 healthy males (mean age 8 y 2 mo; range 5-11 y; SD 1 y 11 mo), recruited from a local education center, participated in the study. We assessed tactile perception using two-point discrimination and stereognosis tests, and manual dexterity using the Pick-Up test with the eyes either open or closed. Analysis of variance was used to compare groups; a p value of less than 0.05 was considered statistically significant. RESULTS: Males with DMD exhibited no impairment in tactile perception, as measured by the two-point discrimination test and the number of objects correctly named in the stereognosis test. Manipulation during stereognosis was statistically slower with both hands (p<0.001), and manual dexterity was much worse in males with DMD when there was no visual feedback (p<0.001). INTERPRETATION: Males with DMD exhibited disturbances in manipulation during stereognosis and dexterity tests. Hand control was highly dependent on visual information rather than on tactile perception. Motor dysfunction in males with DMD, therefore, might be related to altered neural control.
Assuntos
Atividade Motora/fisiologia , Destreza Motora , Distrofia Muscular de Duchenne/fisiopatologia , Percepção do Tato/fisiologia , Percepção Visual/fisiologia , Adolescente , Criança , Pré-Escolar , Discriminação Psicológica , Lateralidade Funcional , Mãos , Humanos , Masculino , Estereognose , Análise e Desempenho de Tarefas , Fatores de TempoRESUMO
Parkinson's disease (PD) symptoms have been collectively ascribed to malfunctioning of dopamine-related nigro-striatal and cortico-striatal loops. However, some doubts about this proposition are raised by controversies about the temporal progression of the impairments, and whether they are concomitant or not. The present study consists of a systematic revision of literature data on both functional PD impairments and dopaminergic medication effects in order to draw a coherent picture about the disease progression. It was done in terms of an explanatory model for the disruption of implicit knowledge acquisition, motor and cognitive impairments, and the effects of dopaminergic medication on these functions. Cognitive impairments arise at early stages of PD and stabilizes while disruption of implicit knowledge acquisition and motor impairments, are still in progression; additionally, dopaminergic medication reduces motor impairments and increases disruption of implicit knowledge acquisition. Since this model revealed consistency and plausibility when confronted with data of others studies not included in model's formulation, it may turn out to be a useful tool for understanding the multifaceted characteristics of PD.
RESUMO
Glucose metabolism and insulin signaling disruptions in the brain have been proposed as a likely etiology of Alzheimer's disease. The aim of the present study was to investigate the time course of cognitive impairments induced by intracerebroventricular injection of streptozotocin (STZ) in rats and correlate them with the ensuing neurodegenerative process. Early and late effects of STZ were evaluated by using the reference and working memory versions of the Morris' water maze task and the evaluation of neurodegenerative markers by immunoblotting and the Fluoro-Jade C histochemistry. The results revealed different types of behavioral and neurodegenerative responses, with distinct time courses. We observed an early disruption on the working memory as early as 3h after STZ injections, which was followed by degenerative processes in the hippocampus at 1 and 15 days after STZ injections. Memory disruption increases over time and culminates with significant changes in amyloid-beta peptide and hyperphosphorylated Tau protein levels in distinct brain structures. These findings add information on the Alzheimer's disease-like STZ animal model and on the mechanisms underlying neurodegenerative processes.