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In mammals, ivermectin acts as a GABAA receptor agonist and stimulates GABA release. Previous studies showed that ivermectin (IVM) reduces sexual performance, impairing the latency to the first mount and intromission. These parameters are usually considered motivational parameters of sexual behavior. However, IVM increases GABAergic activity leading to motor incoordination. Thus, it is reasonable to propose that IVM affects sexual performance via motor incoordination pathways. The present study analyzed ultrasonic vocalization in rats to verify whether IVM impairs sexual behavior via motivational mechanisms or motor impairment. Because sexual experience attenuates the impairment of motor performance, rats with sexual experience were also studied. Sexually naive and experienced rats were administered a therapeutic IVM dose and saline. The rats were exposed to receptive females, and the latency to the first mount was evaluated, followed by the 50-kHz USV test. IVM treatment in naïve rats increased the latency to first to mount relative to Saline naïve rats, while no differences were observed between saline and experienced rats. In naïve-IVM rats, a reduced frequency and total calls and increased mean time of calls occur relative to SAL-naïve rats. Experienced IVM rats did not show differences in the frequency, mean, and maximal calls close to Saline experienced rats. However, an increase in the total calls and the dominant frequency of calls were observed in IVM-experienced rats compared to Saline experienced rats. A negative and positive correlation occurred between the latency to the first mount and USVs in groups with and without ivermectin exposure. Hence, we propose that ivermectin increased the sexual motivation of rats exposed to a female in estrous based in USVs despite an increased latency to the first mount that occurred. The increased latency to the first mount resulted from motor incoordination, as previously observed and proposed by our group.(AU)

Em mamíferos, a ivermectina (IVM) atua como agonista do receptor GABAA e estimula a liberação de GABA. Estudos anteriores mostraram que a IVM reduz o desempenho sexual, prejudicando a latência para a primeira monta e intromissão. Esses parâmetros são geralmente considerados parâmetros motivacionais do comportamento sexual. Por outro lado, a IVM aumenta a atividade GABAérgica levando à incoordenação motora. Assim, é possível que a IVM afete o desempenho sexual devido a um impedimento motor. O presente estudo analisou a vocalização ultrassônica em ratos para verificar se a IVM prejudica o comportamento sexual via mecanismos motivacionais ou comprometimento motor. Uma vez que a experiência sexual atenua o comprometimento do desempenho motor, também foram estudados ratos com experiência sexual. Ratos sexualmente inexperientes e experientes foram administrados com uma dose terapêutica de IVM ou solução salina IVM. Os ratos foram expostos a fêmeas receptivas e foi avaliada a latência para a primeira monta, seguida do teste de vocalização ultrassônica (USV) de 50 kHz. O tratamento com IVM em ratos inexperientes aumentou a latência para a primeira monta em relação a ratos inexperientes tratados com solução salina, enquanto não foram observadas diferenças entre ratos experientes tratados com IVM e solução salina. Em ratos inexperientes tratados com IVM ocorreu redução da frequência e total de USVs, bem como aumento do tempo médio de USVs em relação aos ratos sem experiência. Ratos experientes tratados com IVM não mostraram diferenças na frequência, média e máxima das USVs em relação aos ratos experientes tratados com solução salina; no entanto, observou-se aumento no total de USVs e na frequência dominante de USVS em ratos experientes tratados com IVM comparados aos experientes tratados com solução salina. Observou-se correlação negativa e positiva entre a latência para a primeira monta e USVs nos grupos sem e com experiência tratados com IVM, respectivamente. Assim, propomos que a IVM aumentou a motivação sexual de ratos expostos a uma fêmea em estro com base em USVs, apesar de apresentar aumento na latência para a primeira monta. O aumento da latência para a primeira monta foi atribuída à incoordenação motora, conforme observado anteriormente e proposto por nosso grupo.(AU)

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Background: The West Nile virus (WNV) antibodies were reported in Brazil in the serum samples taken from horses andbirds in the Midwest region and Paraíba state in 2008 and 2013, respectively. In 2014, the first human case was confirmedin a rural worker in the state of Piauí and, in 2018, the virus was isolated from the central nervous system of a horse withnervous symptoms in the state of Espírito Santo. The virus is a member of the Flaviviridae family of the genus Flavivirus(neurotropic), infecting several mammalian species, with humans and horses being the most susceptible. Approximately35% of horses develop clinical signs, thus they are considered the best sentinels for this disease. The aim of this case reportis to describe the first confirmed cases of West Nile Fever (WNF) in two horses in the state of São Paulo.Cases: Two horses with neurological symptoms were treated at the Veterinary Hospital of Cruzeiro do Sul University (SãoPaulo, SP), in 2019. Both horses came from neighboring regions that have a large Atlantic Forest preservation area and arealso routes for migratory birds, known to be competent hosts for transmitting the West Nile Fever virus, such as the swallow,the falcon and the hawk. The first one had symptoms, such as weakness and sporadic seizures; however, after recovering,it was hospitalized a few days later due to kidney failure and laminitis. The second one showed incoordination, pelviclimb weakness, and was walking in circles, evolving to seizures. Both animals were euthanized, and their central nervoussystem samples and total blood samples were tested for rabies, herpes virus, and WNV; the first 2 tests showed negativeresults. Ribonucleic acids (RNA) were extracted from erythrocytes using the polymerase...

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Background: The West Nile virus (WNV) antibodies were reported in Brazil in the serum samples taken from horses andbirds in the Midwest region and Paraíba state in 2008 and 2013, respectively. In 2014, the first human case was confirmedin a rural worker in the state of Piauí and, in 2018, the virus was isolated from the central nervous system of a horse withnervous symptoms in the state of Espírito Santo. The virus is a member of the Flaviviridae family of the genus Flavivirus(neurotropic), infecting several mammalian species, with humans and horses being the most susceptible. Approximately35% of horses develop clinical signs, thus they are considered the best sentinels for this disease. The aim of this case reportis to describe the first confirmed cases of West Nile Fever (WNF) in two horses in the state of São Paulo.Cases: Two horses with neurological symptoms were treated at the Veterinary Hospital of Cruzeiro do Sul University (SãoPaulo, SP), in 2019. Both horses came from neighboring regions that have a large Atlantic Forest preservation area and arealso routes for migratory birds, known to be competent hosts for transmitting the West Nile Fever virus, such as the swallow,the falcon and the hawk. The first one had symptoms, such as weakness and sporadic seizures; however, after recovering,it was hospitalized a few days later due to kidney failure and laminitis. The second one showed incoordination, pelviclimb weakness, and was walking in circles, evolving to seizures. Both animals were euthanized, and their central nervoussystem samples and total blood samples were tested for rabies, herpes virus, and WNV; the first 2 tests showed negativeresults. Ribonucleic acids (RNA) were extracted from erythrocytes using the polymerase...(AU)

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Introduction: Obesity promotes hypothalamic inflammation and local morphological changes in astrocytes, including the increased expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP), which is seen as a sign of neuroinflammation.Objective: This study aimed to observe the astrocytic expression of GFAP in different brain areas from female rats that received a hypercaloric (HD) or a normocaloric (ND) diet during puberty (F0 generation) as well as in their male pups (F1 generation).Methods: Female rats received highly palatable HD (Ensure®) or ND from postnatal day (PND) 23-65. On PND90-95, some were euthanized for the immunohistochemical study and some were mated to obtain the F1 generation. Male pups were immunochallenged on PND50 with lipopolysaccharide (LPS, 100 µg/kg) or 0.9% saline solution (1 mL/kg) intraperitoneal injection. Body weight (BW) and retroperitoneal fat weight (RFW) were recorded on PND95 for F0 generation and on PND50 for F1 generation. GFAP expression for both generations was assessed by morphometry in the parietal/frontal cortex, corpus callosum, nucleus accumbens, arcuate/periventricular nuclei of hypothalamus, pons, molecular/granular layers of cerebellum.Results: Female rats fed with HD presented a significant increase in the GFAP expression in all evaluated areas as well as in the RFW. Male rats born from mothers that received HD showed decreased GFAP expression, BW and RFW when treated with LPS in relation to those from mothers fed with ND.Discussion: HD induced astrogliosis in several brain areas in females from F0 generation and an adaptive phenotypic change of decreased GFAP expression in males from F1 generation after LPS challenge.

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Although there has been marked progress in the survival rates of children with cancer in recent decades, it is recognized that chemotherapy administered during childhood and adolescence can exert significant central nervous system (CNS) toxicity. It may, for example, affect the neurocognitive functions of the survivors, even with a loss in school/academic performance as children and/or lately in adulthood, thus influencing the quality of life of these individuals. Animal models and clinical studies have allowed the search for an understanding of the pathogenic mechanisms that involve the cognitive deficits induced by chemotherapy in children and adolescents, and also contribute to the development of drugs aiming to prevent or minimize the CNS side effects in these patients. This review aims to present studies describing the cognitive dysfunction induced by chemotherapy applied in the periods of childhood and puberty, discussing the possible incriminated mechanisms, their repercussions in adult life and the importance of pre-clinical studies in vivo in the search for therapeutic protocols that attenuate or prevent the occurrence of this phenomenon.

Embora tenha havido nas últimas décadas um progresso marcante nas taxas de sobrevida de crianças com câncer, é reconhecido que a quimioterapia administrada durante o período da infância e da adolescência pode exercer significativa toxicidade sobre o sistema nervoso central (SNC). Pode, por exemplo, afetar as funções neurocognitivas dos sobreviventes, inclusive com prejuízo no rendimento escolar/acadêmico ainda quando crianças e/ou tardiamente, em idade adulta, dessa forma influenciando de maneira expressiva a qualidade de vida futura desses indivíduos. Modelos animais e estudos clínicos têm permitido a busca da compreensão dos mecanismos patogênicos que envolvem os déficits cognitivos induzidos pela quimioterapia em crianças e adolescentes, contribuindo ainda para o desenvolvimento de drogas que visem a prevenir ou minimizar os efeitos colaterais no SNC desses pacientes. Na presente revisão, busca-se apresentar estudos que descrevem a disfunção cognitiva tardia induzida pela quimioterapia aplicada no período da infância e da adolescência, discutindo os possíveis mecanismos incriminados, suas repercussões na vida adulta e a importância dos estudos pré-clínicos in vivo na busca de protocolos terapêuticos que atenuem ou impeçam a ocorrência desse fenômeno.

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OBJECTIVE: Hypothalamic inflammation and glial fibrillary acidic protein (GFAP) overexpression in astrocytes are well described in obese animals, as are some cognitive and memory deficits. As the hippocampus plays important roles in the consolidation of information, this investigation aimed to observe the memory function and the astrocyte expression of GFAP in the hippocampus of rats that received either a hypercaloric or a normocaloric diet. METHODS: Adult male Wistar rats received a high-fat (cafeteria) or a standard diet for 60 days. On the 61st day, the rats were submitted to the novel object recognition (NOR) test at three and 24 hours after the first contact with objects, to assess short-term and long-term memory, respectively. Thereafter, the rats were euthanized and their brains were collected for GFAP immunohistochemical investigation in the hippocampus (CA1, CA2, CA3 areas) and hypothalamus (periventricular and arcuate nuclei). Astrocytic reactivity was assessed by morphometry. Different white adipose tissue depots and brown adipose tissue were weighed to calculate the adiposity index. RESULTS: The hypercaloric diet increased body weight gain, adiposity index, white adipose tissue weight (epididymal, subcutaneous and retroperitoneal) and brown adipose tissue weight. Rats fed with the hypercaloric diet showed short-term and long-term memory impairments in the NOR test, as well as increased GFAP expression in astrocytes from all analyzed hypothalamic and hippocampal areas. CONCLUSION: This astrogliosis suggests that the neuroinflammatory response also occurs in the hippocampus and may be involved in the memory losses observed in obese/overweight animals.

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ABSTRACT Objective: Hypothalamic inflammation and glial fibrillary acidic protein (GFAP) overexpression in astrocytes are well described in obese animals, as are some cognitive and memory deficits. As the hippocampus plays important roles in the consolidation of information, this investigation aimed to observe the memory function and the astrocyte expression of GFAP in the hippocampus of rats that received either a hypercaloric or a normocaloric diet. Methods: Adult male Wistar rats received a high-fat (cafeteria) or a standard diet for 60 days. On the 61st day, the rats were submitted to the novel object recognition (NOR) test at three and 24 hours after the first contact with objects, to assess short-term and long-term memory, respectively. Thereafter, the rats were euthanized and their brains were collected for GFAP immunohistochemical investigation in the hippocampus (CA1, CA2, CA3 areas) and hypothalamus (periventricular and arcuate nuclei). Astrocytic reactivity was assessed by morphometry. Different white adipose tissue depots and brown adipose tissue were weighed to calculate the adiposity index. Results: The hypercaloric diet increased body weight gain, adiposity index, white adipose tissue weight (epididymal, subcutaneous and retroperitoneal) and brown adipose tissue weight. Rats fed with the hypercaloric diet showed short-term and long-term memory impairments in the NOR test, as well as increased GFAP expression in astrocytes from all analyzed hypothalamic and hippocampal areas. Conclusion: This astrogliosis suggests that the neuroinflammatory response also occurs in the hippocampus and may be involved in the memory losses observed in obese/overweight animals.

RESUMO Objetivo: A inflamação hipotalâmica e a superexpressão da proteína glial fibrilar ácida (GFAP) em astrócitos são bem descritas em animais obesos, assim como déficits cognitivos e de memória. Como o hipocampo desempenha importante papel na consolidação de informações, esta investigação teve como objetivo observar a função da memória e a expressão astrocitária da GFAP no hipocampo de ratos que receberam dieta hipercalórica ou normocalórica. Métodos: Ratos Wistar machos adultos receberam dieta rica em gordura (cafeteria) ou dieta padrão por 60 dias. No 61º dia, os ratos foram submetidos ao teste de reconhecimento de objetos (NOR) 3 e 24 horas após o primeiro contato com os objetos, para avaliação da memória de curto e de longo prazo, respectivamente. Após, os ratos foram eutanasiados e os encéfalos coletados para pesquisa imuno-histoquímica da expressão astrocitária de GFAP no hipocampo (áreas CA1, CA2 e CA3) e no hipotálamo (núcleos periventricular e arqueado). A reatividade astrocitária foi avaliada por morfometria. Diferentes depósitos de tecido adiposo branco e marrom foram pesados para calcular o índice de adiposidade. Resultados: A dieta hipercalórica aumentou o ganho de peso corporal, o índice de adiposidade, o peso do tecido adiposo branco (epididimal, subcutâneo e retroperitoneal) e marrom. Ratos alimentados com dieta hipercalórica apresentaram prejuízos na memória de curto e longo prazo no teste NOR e aumento da expressão de GFAP em astrócitos de todas as áreas hipotalâmicas e hipocampais analisadas. Conclusão: Esta astrogliose sugere que a resposta neuroinflamatória também ocorre no hipocampo, podendo estar envolvida nas perdas de memória observadas em animais obesos/com sobrepeso.

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OBJECTIVES: The purpose of this study was to evaluate some indicators of redox status, and inflammation on different regions of the central nervous system (CNS) of obese rats treated with green tea (GT). We hypothesized that obesity could affect the redox balance in different brain regions due to the diverse nature of the cells as well as the selective neuronal vulnerability to oxidative stress, and GT could triggers benefits effects restoring the redox status. METHODS: Male Wistar rats were treated with GT by gavage (12 weeks/5 days/week; 500 mg/kg of body weight) and obesity was induced by cafeteria diet (8 weeks). After this period, the animals were killed and brain tissue (cerebral cortex, cerebellum, and brainstem) was removed to evaluate oxidative stress and inflammation (cytokine release). RESULTS: We showed that the cafeteria diet had little effect on redox balance in the cerebral cortex and cerebellum; however, the brainstem was the region of the CNS most sensitive to cafeteria diet-induced redox unbalance. GFAP expression was increased in the cerebral cortex of obese rats and reduced by GT. It was also evident that GT treatment had numerous beneficial effects against oxidative damage to biomolecules in all brain regions analyzed. DISCUSSION: Our study established that different CNS regions show selective neuronal vulnerability when exposed to a diet enriched with fats and sugars, and the beneficial effect of GT was similar among these regions. We conclude that GT could be a good strategy for improving and maintaining brain function under healthy and pathological conditions.

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Although there has been marked progress in the survival rates of children with cancer in recent decades, it is recognized that chemotherapy administered during childhood and adolescence can exert significant central nervous system (CNS) toxicity. It may, for example, affect the neurocognitive functions of the survivors, even with a loss in school/academic performance as children and/or lately in adulthood, thus influencing the quality of life of these individuals. Animal models and clinical studies have allowed the search for an understanding of the pathogenic mechanisms that involve the cognitive deficits induced by chemotherapy in children and adolescents, and also contribute to the development of drugs aiming to prevent or minimize the CNS side effects in these patients. This review aims to present studies describing the cognitive dysfunction induced by chemotherapy applied in the periods of childhood and puberty, discussing the possible incriminated mechanisms, their repercussions in adult life and the importance of pre-clinical studies in vivo in the search for therapeutic protocols that attenuate or prevent the occurrence of this phenomenon.(AU)

Embora tenha havido nas últimas décadas um progresso marcante nas taxas de sobrevida de crianças com câncer, é reconhecido que a quimioterapia administrada durante o período da infância e da adolescência pode exercer significativa toxicidade sobre o sistema nervoso central (SNC). Pode, por exemplo, afetar as funções neurocognitivas dos sobreviventes, inclusive com prejuízo no rendimento escolar/acadêmico ainda quando crianças e/ou tardiamente, em idade adulta, dessa forma influenciando de maneira expressiva a qualidade de vida futura desses indivíduos. Modelos animais e estudos clínicos têm permitido a busca da compreensão dos mecanismos patogênicos que envolvem os déficits cognitivos induzidos pela quimioterapia em crianças e adolescentes, contribuindo ainda para o desenvolvimento de drogas que visem a prevenir ou minimizar os efeitos colaterais no SNC desses pacientes. Na presente revisão, busca-se apresentar estudos que descrevem a disfunção cognitiva tardia induzida pela quimioterapia aplicada no período da infância e da adolescência, discutindo os possíveis mecanismos incriminados, suas repercussões na vida adulta e a importância dos estudos pré-clínicos in vivo na busca de protocolos terapêuticos que atenuem ou impeçam a ocorrência desse fenômeno.(AU)

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Obesity is associated with a chronic and low-grade inflammatory response in the hypothalamus, where astrogliosis occurs with the upregulation of the astrocyte structural protein GFAP. As propentofylline (PPF) has inhibitory effects on astrocyte and microglial activation during inflammation, this study aimed to investigate if this xanthine derivative could decrease the astrocyte reaction induced by a hypercaloric diet (HD). Male Wistar rats were divided into four groups: NDS - rats receiving a normocaloric diet (ND) and daily saline solution; NDP - rats receiving ND and daily PPF (12.5 mg/kg/day, intraperitoneal route); HDS - rats receiving HD and saline solution, HDP - rats receiving HD and PPF. On the 21st day, rats were anesthetized, and perfused, and brains were collected for GFAP immunohistochemical study in the hypothalamus. Results showed that HD induced increased weight gain and hypothalamic astrogliosis. Propentofylline decreased the expression of GFAP in the HDP group, although it did not affect the weight gain induced by this diet.

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ABSTRACT Obesity is associated with a chronic and low-grade inflammatory response in the hypothalamus, where astrogliosis occurs with the upregulation of the astrocyte structural protein GFAP. As propentofylline (PPF) has inhibitory effects on astrocyte and microglial activation during inflammation, this study aimed to investigate if this xanthine derivative could decrease the astrocyte reaction induced by a hypercaloric diet (HD). Male Wistar rats were divided into four groups: NDS - rats receiving a normocaloric diet (ND) and daily saline solution; NDP - rats receiving ND and daily PPF (12.5 mg/kg/day, intraperitoneal route); HDS - rats receiving HD and saline solution, HDP - rats receiving HD and PPF. On the 21st day, rats were anesthetized, and perfused, and brains were collected for GFAP immunohistochemical study in the hypothalamus. Results showed that HD induced increased weight gain and hypothalamic astrogliosis. Propentofylline decreased the expression of GFAP in the HDP group, although it did not affect the weight gain induced by this diet.

RESUMO A obesidade está associada com uma resposta inflamatória crônica e de baixo grau no hipotálamo, onde ocorre astrogliose com a superexpressão da proteína astrocitária GFAP. Como a propentofilina (PPF) possui efeitos inibitórios sobre a ativação astrocitária e microglial durante a inflamação, este estudo visou a investigar se esta xantina podia diminuir a reação astrocitária induzida pela dieta hipercalórica (HD). Ratos Wistar machos foram divididos em 4 grupos: NDS- ratos recebendo dieta normocalórica (ND) e solução salina diária; NDP- ratos recebendo ND e PPF diária (12.5 mg/kg/dia, via intraperitoneal); HDS- ratos recebendo HD e solução salina, HDP- ratos recebendo HD e PPF. No 21° dia, os ratos foram perfundidos e os encéfalos, coletados para estudo imuno-histoquímico para a GFAP no hipotálamo. Os resultados mostram que a HD induziu aumento do ganho de peso e astrogliose no hipotálamo. A PPF diminuiu a expressão de GFAP no grupo HD, embora não tenha afetado o ganho de peso induzido por esta dieta.

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Ivermectin (IVM) is an antiparasitic agent widely used in agricultural, domestic animals and in human clinical practice. In the present study, the temporal effects of therapeutic doses of IVM in the morphometric and histological assessment of testis were studied to verify if IVM acute administration impaired the spermatogenesis and spermiogenesis of adult rats, if these effects are reversible. The testosterone levels and the plasmatic IVM levels were assessed. The results show: 1) IVM acute exposure, mainly in the higher dose, reduced the testicular volume, the tubular diameter and the germinal epithelium height; 2) no interferences on Leydig cells frequency; 3) histological studies show that tubular sections containing several histological changes indicative of spermatogenesis interruption, such as disorganization of germinal epithelium, vacuolar degeneration of the germ cells and sloughing of cells into the tubular lumen; 4) no differences in testosterone levels; 5) The IVM plasmatic levels were significantly reduced at 72h after the 0.2mg/kg. It was concluded that acute IVM impaired the spermatogenesis and spermiogenesis of rats. Probably these effects were not consequence of IVM at the Leydig cells because no effects were observed at this level. Finally, our results suggest that some testicular effects are reversible and correlated with the plasmatic levels of IVM.

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A doxorrubicina (DOX), um agente interativo da topoisomerase, é comumente utilizada no tratamento de vários tipos de câncer sólidos e hematológicos. Esta droga é conhecida por causar prejuízos cognitivos em indivíduos submetidos à quimioterapia de longo prazo (déficits também chamados de chemobrain). Frente à relativa inexistência de estratégias preventivas ou terapêuticas eficazes para evitar o desenvolvimento do chemobrain, modelos experimentais in vitro e in vivo têm sido empregados na busca da compreensão dos mecanismos subjacentes a tal fenômeno.  A presente revisão visa a apresentar estudos envolvendo a administração de DOX, como base para o possível entendimento dos processos que conduzem aos prejuízos cognitivos induzidos pela quimioterapia.(AU)

Doxorubicin (DOX), a topoisomerase interactive agent, is commonly used to treat several types of solid and hematological cancers. This drug is known to cause cognitive impairments in individuals submitted to long-term chemotherapy (deficits also called as chemobrain). Given the relative absence of effective preventive or therapeutic strategies to avoid the development of chemobrain, in vitro and in vivo experimental models have been employed in the search for an understanding of the mechanisms underlying such phenomena. The present review aims to present studies involving the administration of DOX, as a basis for the possible comprehension of the processes leading to the cognitive impairments induced by chemotherapy.(AU)

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A doxorrubicina (DOX), um agente interativo da topoisomerase, é comumente utilizada no tratamento de vários tipos de câncer sólidos e hematológicos. Esta droga é conhecida por causar prejuízos cognitivos em indivíduos submetidos à quimioterapia de longo prazo (déficits também chamados de chemobrain). Frente à relativa inexistência de estratégias preventivas ou terapêuticas eficazes para evitar o desenvolvimento do chemobrain, modelos experimentais in vitro e in vivo têm sido empregados na busca da compreensão dos mecanismos subjacentes a tal fenômeno.  A presente revisão visa a apresentar estudos envolvendo a administração de DOX, como base para o possível entendimento dos processos que conduzem aos prejuízos cognitivos induzidos pela quimioterapia.

Doxorubicin (DOX), a topoisomerase interactive agent, is commonly used to treat several types of solid and hematological cancers. This drug is known to cause cognitive impairments in individuals submitted to long-term chemotherapy (deficits also called as chemobrain). Given the relative absence of effective preventive or therapeutic strategies to avoid the development of chemobrain, in vitro and in vivo experimental models have been employed in the search for an understanding of the mechanisms underlying such phenomena. The present review aims to present studies involving the administration of DOX, as a basis for the possible comprehension of the processes leading to the cognitive impairments induced by chemotherapy.

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OBJECTIVE: The present study evaluated the nociceptive response induced by dentin hypersensitivity after dental erosion in rats that were exhibited to unpredictable chronic mild stress (UCMS)-induced depressive-like behavior. DESIGN: Adult male rats were subjected to UCMS (depression [D] group) or not (no depression [ND] group) for 30days and received either acidic solution to induce dental erosion (E) or water (W), thus forming the WND, END, WD, and ED groups. After the end of treatment, depressive-like parameters (i.e., sucrose preference and immobility in the forced swim test) and dentin hypersensitivity were evaluated. Plasma tumor necrosis factor α (TNF-α) and corticosterone levels were measured, and astrocytic glial fibrillary acidic protein (GFAP) expression was evaluated in the prefrontal cortex, hippocampus, amygdala, and hypothalamus. RESULTS: Administration of the acidic solution potentiated dentin hypersensitivity and increased corticosterone levels in the ED group compared with the WD group. TNF-α levels only increased in the WD group. The ED group exhibited an increase in astrocytic GFAP expression in the hypothalamus and prefrontal cortex but decreases in the hippocampus. CONCLUSIONS: These results suggest that UCMS exacerbated the nociceptive response associated with dentin hypersensitivity, concomitant with an increase in plasma corticosterone levels. Hypothalamic and prefrontal cortex astrogliosis in the ED group may be attributable to the increase in corticosterone associated to UCMS procedure. The reduction of astrocytic GFAP expression in the hippocampus in the ED group supports the association between dentin hypersensitivity and depression.

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ABSTRACT Pro-inflammatory cytokines and glial cells, especially microglial cells, have been implicated in persistent pain sensitization. Less is known about the role of astrocytes in pain regulation. This study aimed to observe the expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP) and the serum levels of interleukin 1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) after short-term administration of central pain relievers in rats not submitted to noxious stimuli. Male Wistar rats were divided into five groups, receiving for nine days- (1) amitriptyline (Amt-10 mg/kg/day, by gavage); (2) gabapentin (Gb-60 mg/kg/day, by gavage; (3) methadone (Me-4.5 mg/kg/day, intraperitoneal route [IP]); (4) morphine (Mo-10 mg/kg/day, IP); or (5) 0.9% saline solution, IP. Brain samples were collected for immunohistochemical study of GFAP expression in the mesencephalon and nucleus accumbens (NAc). The area of GFAP-positive cells was calculated using MetaMorph software and serum levels of IL-1ß and TNF-α were measured by enzyme-linked immunosorbent assay. Serum TNF-α levels were decreased in the groups treated with Mo, Me and Gb, but not in the Amt-treated group. IL-1ß decreased only in rats treated with Me. The astrocytic expression of GFAP was decreased in the brainstem with all drugs, while it was increased in the NAc with Amt, Me and Mo

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OBJECTIVE: This study aimed to evaluate the effect of propentofylline administration on astrocytic response following gliotoxic injury. METHOD: Wistar rats were injected with ethidium bromide into the cisterna pontis and treated or not with propentofylline (12.5mg/kg/day, intraperitoneal) during the experimental period. Brainstem sections were collected from 15 to 31 days after gliotoxic injection and processed for GFAP immunohistochemistry. RESULTS AND CONCLUSION: Results demonstrate that propentofylline decreased astrocytic activation until the 21st day, suggesting that this drug may have a role in reducing glial scar development following injury.

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ABSTRACT Propentofylline is a xanthine derivative that depresses activation of glial cells, whose responses contribute to neural tissue damage during inflammation. Ethidium bromide injection into the central nervous system induces local oligodendroglial and astrocytic loss, resulting in primary demyelination, neuroinflammation and blood-brain barrier disruption. Surviving astrocytes present a vigorous reaction around the injury site with increased immunoreactivity to glial fibrillary acidic protein (GFAP). Objective This study aimed to evaluate the effect of propentofylline administration on astrocytic response following gliotoxic injury. Method Wistar rats were injected with ethidium bromide into the cisterna pontis and treated or not with propentofylline (12.5mg/kg/day, intraperitoneal) during the experimental period. Brainstem sections were collected from 15 to 31 days after gliotoxic injection and processed for GFAP immunohistochemistry. Results and Conclusion Results demonstrate that propentofylline decreased astrocytic activation until the 21st day, suggesting that this drug may have a role in reducing glial scar development following injury.

RESUMO A propentofilina é uma xantina que deprime a ativação das células gliais, cujas respostas contribuem para o dano neural durante inflamação. A injeção de brometo de etídio no sistema nervoso central induz a perda oligodendroglial e astrocitária, resultando em desmielinização, neuroinflamação e ruptura da barreira hematoencefálica. Os astrócitos sobreviventes apresentam vigorosa reação ao redor da lesão com aumento da imunorreatividade à proteína glial fibrilar ácida (GFAP). Objetivo Este estudo objetivou avaliar o efeito da propentofilina sobre a resposta astrocitária após injúria gliotóxica. Método Ratos Wistar foram injetados com brometo de etídio na cisterna basal e tratados ou não com propentofilina (12.5mg/kg/dia, intraperitoneal). Amostras do tronco encefálico foram coletadas dos 15 aos 31 dias pós-injeção do gliotóxico e processadas para estudo ultraestrutural e imuno-histoquímico para GFAP. Resultados e Conclusão Os resultados demonstram que a propentofilina reduziu a ativação astrocitária até o 21o dia, sugerindo que essa droga pode atuar na redução da cicatriz glial após injúria.

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A narcolepsia canina é um distúrbio neurológico que afeta o surgimento e a organização do sono, sendo caracterizada por sonolência diurna excessiva, cataplexia e prováveis alucinações hipnagógicas. Em cães das raças dobermann e labrador, a narcolepsia é transmitida de forma hereditária pelo gene recessivo de penetrância completa canarc-1, causando mutação nos receptores de hipocretina-2, um neuropeptídeo que ativa os neurônios que impedem a entrada no sono REM. O diagnóstico pode ser feito por meio da observação dos sintomas, sendo a cataplexia um fator-chave para o diagnóstico da doença. A narcolepsia deve ser cuidadosamente diferenciada de outras enfermidades neurológicas e distúrbios paralíticos reversíveis. O tratamento é paliativo e baseia-se na administração de estimulantes do sistema nervoso central (SNC) e antidepressivos tricíclicos.

Canine narcolepsy is a neurological disorder that affects the appearance and organization of sleep. It is characterized by excessive daytime sleepiness, cataplexy and hypnagogic hallucinations. In Dobermann and Labrador breeds, narcolepsy is transmitted hereditarily by the canarc-1recessive gene, which has complete penetrance and causes a mutation in the receptor for hypocretin-2, a neuropeptide that prevents entry into REM sleep by activating specific neurons. Diagnosis can be achieved by observing the symptoms. Cataplexy is a key factor for diagnosis of narcolepsy and must be carefully distinguished from other neurological diseases and reversible paralytic disorders. Treatment is palliative and based on the administration of stimulants of the central nervous system (CNS) and tricyclic antidepressants.

La narcolepsia canina es una alteración neurológica que afecta la aparición y organización del sueño, que se caracteriza por una excesiva somnolencia diurna, cataplejía y probables alucinaciones hipnagógicas. En perros de las razas Doberman y Labrador, la narcolepsia se transmite de forma hereditaria a través del gen recesivo de penetrancia completa canarc-1, que provoca mutación de los receptores de hipocretina-2, un neuropéptido que activa las neuronas que impiden la entrada en sueño REM. El diagnostico se puede realizar a través de la sintomatología y la cataplejía representa un factor llave para llegar al mismo. La narcolepsia debe ser cuidadosamente diferenciada de otras enfermedades neurológicas y de alteraciones paralíticas reversibles. El tratamiento es paliativo, y se realiza a través de estimulantes del sistema nervioso central y antidepresivos tricíclicos.

Asunto(s)

RESUMEN

A narcolepsia canina é um distúrbio neurológico que afeta o surgimento e a organização do sono, sendo caracterizada por sonolência diurna excessiva, cataplexia e prováveis alucinações hipnagógicas. Em cães das raças dobermann e labrador, a narcolepsia é transmitida de forma hereditária pelo gene recessivo de penetrância completa canarc-1, causando mutação nos receptores de hipocretina-2, um neuropeptídeo que ativa os neurônios que impedem a entrada no sono REM. O diagnóstico pode ser feito por meio da observação dos sintomas, sendo a cataplexia um fator-chave para o diagnóstico da doença. A narcolepsia deve ser cuidadosamente diferenciada de outras enfermidades neurológicas e distúrbios paralíticos reversíveis. O tratamento é paliativo e baseia-se na administração de estimulantes do sistema nervoso central (SNC) e antidepressivos tricíclicos.(AU)

Canine narcolepsy is a neurological disorder that affects the appearance and organization of sleep. It is characterized by excessive daytime sleepiness, cataplexy and hypnagogic hallucinations. In Dobermann and Labrador breeds, narcolepsy is transmitted hereditarily by the canarc-1recessive gene, which has complete penetrance and causes a mutation in the receptor for hypocretin-2, a neuropeptide that prevents entry into REM sleep by activating specific neurons. Diagnosis can be achieved by observing the symptoms. Cataplexy is a key factor for diagnosis of narcolepsy and must be carefully distinguished from other neurological diseases and reversible paralytic disorders. Treatment is palliative and based on the administration of stimulants of the central nervous system (CNS) and tricyclic antidepressants.(AU)

La narcolepsia canina es una alteración neurológica que afecta la aparición y organización del sueño, que se caracteriza por una excesiva somnolencia diurna, cataplejía y probables alucinaciones hipnagógicas. En perros de las razas Doberman y Labrador, la narcolepsia se transmite de forma hereditaria a través del gen recesivo de penetrancia completa canarc-1, que provoca mutación de los receptores de hipocretina-2, un neuropéptido que activa las neuronas que impiden la entrada en sueño REM. El diagnostico se puede realizar a través de la sintomatología y la cataplejía representa un factor llave para llegar al mismo. La narcolepsia debe ser cuidadosamente diferenciada de otras enfermedades neurológicas y de alteraciones paralíticas reversibles. El tratamiento es paliativo, y se realiza a través de estimulantes del sistema nervioso central y antidepresivos tricíclicos.(AU)

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