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1.
Homeopathy ; 110(4): 244-255, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34474498

RESUMO

INTRODUCTION: Finding solutions to mitigate the impact of pollution on living systems is a matter of great interest. Homeopathic preparations of toxic substances have been described in the literature as attenuation factors for intoxication. Herein, an experimental study using Artemia salina and mercury chloride was developed as a model to identify aspects related to bioresilience. AIMS: The aim of the study was to describe the effects of homeopathic Mercurius corrosivus (MC) on Artemia salina cysts hatching and on mercury bioavailability. METHODS: Artemia salina cysts were exposed to 5.0 µg/mL of mercury chloride during the hatching phase. MC potencies (6cH, 30cH, and 200cH) were prepared in sterile purified water and poured into artificial sea water. Different controls were used (non-challenged cysts and challenged cysts treated with water, succussed water, and Ethilicum 1cH). Four series of nine experiments were performed to evaluate the percentage of cyst hatching. Soluble total mercury (THg) levels and precipitated mercury content were also evaluated. Solvatochromic dyes were used to check for eventual physicochemical markers of MC biological activity. RESULTS: Significant delay (p < 0.0001) in cyst hatching was observed only after treatment with MC 30cH, compared with controls. This result was associated with an increase of THg concentration in water (p = 0.0018) and of chlorine/oxygen ratio (p < 0.0001) in suspended micraggregates, suggesting changes in mercury bioavailability. A specific interaction of MC 30cH with the solvatochromic dye ET33 (p = 0.0017) was found. CONCLUSION: Changes in hatching rate and possible changes in Hg bioavailability are postulated as protective effects of MC 30cH on Artemia salina, by improving its natural bioresilience processes.

2.
Brain Behav Immun ; 87: 489-497, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32006614

RESUMO

Considering all mental and addictive disorders, depression is the most responsible for years of life lost due to premature mortality and disability. Antidepressant drugs have limited effectiveness. Depression can be triggered by immune/inflammatory factors. Zinc and paracetamol interfere with immune system and have demonstrated beneficial effects on depression treatment when administered concomitant with antidepressant drugs. The objective of this study was to test zinc and/or paracetamol as treatments of depressive-like behavior, sickness behavior, and anxiety in rats, as well as to understand the central and peripheral mechanisms involved. Sickness behavior and depressive-like behavior were induced in rats with repetitive lipopolysaccharide (LPS, 1 mg/kg for two consecutive days) administrations. Rats received zinc and/or paracetamol for three consecutive days. Sickness behavior (daily body weight and open field general activity); anxiety (light-dark test); depressive-like/antidepressant behavior (forced swim test); plasma corticosterone and interferon (IFN)-gamma levels; and glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH) brain expression were evaluated. LPS induced sickness behavior and depressive-like behavior, as well as elevated IFN-gamma levels and increased GFAP expression. Zinc prevented both behavioral and biochemical impairments. Paracetamol and zinc + paracetamol association induced only slight beneficial effects. Anxiety, corticosterone, and TH do not seem be related with depression and the other behavioral and neuroimmune changes. In conclusion, zinc treatment was beneficial for sickness behavior and depressive-like behavior without concomitant administration of antidepressants. IFN-gamma and GFAP were linked with the expression of sickness behavior and depressive-like behavior and were also involved with the antidepressant effects. Therefore, zinc, IFN-gamma, and GFAP pathways should be considered for depression treatment.


Assuntos
Comportamento de Doença , Interferon gama , Acetaminofen , Animais , Comportamento Animal , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Gliose , Lipopolissacarídeos , Ratos , Zinco
3.
Epilepsy Behav ; 105: 106945, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32109856

RESUMO

The tremor mutant phenotype results from an autosomal recessive spontaneous mutation arisen in a Swiss-Webster mouse colony. The mutant mice displayed normal development until three weeks of age when they began to present motor impairment comprised by whole body tremor, ataxia, and decreased exploratory behavior. These features increased in severity with aging suggesting a neurodegenerative profile. In parallel, they showed audiogenic generalized clonic seizures. Results from genetic mapping identified the mutation tremor on chromosome 14, in an interval of 5 cM between D14Mit37 (33.21 cM) and D14Mit115 (38.21 cM), making Early Growth Response 3 (Egr3) the main candidate gene. Comparing with wild type (WT) mice, the tremor mice showed higher hippocampal gene expression of Egr3 and Gabra1 and increased concentrations of noradrenalin (NOR; p = .0012), serotonin (5HT; p = .0083), 5-hydroxyindoleacetic acid (5-HIAA; p = .0032), γ-amino butyric acid (GABA; p = .0123), glutamate (p = .0217) and aspartate (p = .0124). In opposition, the content of glycine (p = .0168) and the vanillylmandelic acid (VMA)/NOR ratio (p = .032) were decreased. Regarding to dopaminergic system, neither dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents nor the turnover rate of DA showed statistically significant differences between WT and mutant mice. Data demonstrated that audiogenic seizures of tremor mice are associated with progressive motor impairment as well as to hippocampal alterations of the Egr3 and Gabra1 gene expression and amino acid and monoamine content. In addition, the tremor mice could be useful for study of neurotransmission pathways as modulators of epilepsy and the pathogenesis of epilepsies occurring with generalized clonic seizures.


Assuntos
Estimulação Acústica/efeitos adversos , Epilepsia Reflexa/genética , Epilepsia Reflexa/metabolismo , Mutação/genética , Tremor/genética , Tremor/metabolismo , Animais , Modelos Animais de Doenças , Dopamina/metabolismo , Feminino , Ácido Glutâmico/metabolismo , Hipocampo/química , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Norepinefrina/metabolismo , Convulsões/genética , Convulsões/metabolismo , Serotonina/metabolismo
4.
Nutr Neurosci ; 23(6): 411-421, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30126346

RESUMO

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.


Assuntos
Astrócitos/metabolismo , Encéfalo/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Obesidade/metabolismo , Animais , Encefalite/metabolismo , Ingestão de Energia , Feminino , Gliose/metabolismo , Lipopolissacarídeos , Masculino , Ratos Wistar
5.
Behav Brain Res ; 378: 112233, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-31521736

RESUMO

Doxorubicin (DOX) is known to cause cognitive impairments in patients submitted to long-term chemotherapy (deficits also known as chemobrain). The present study investigated whether DOX administration could affect behavior and brain morphology, as well as oxidative and inflammatory status in rats. Male Wistar rats were injected with DOX (2.5 mg/kg/week, 4 weeks, i.p.) or saline. Behavioral analyses were performed. Brains were collected and analyzed by hematoxylin-eosin and luxol fast blue staining techniques and by immunohistochemistry (for glial fibrillary acidic protein expression in astrocytes; GFAP). Serum and brain levels of TNF-α, IL-1ß, IL-6, IL-8, IL-10 and CXCL-1 were determined. Oxidative parameters, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), nitric oxide (NO•), brain iron and ferritin levels, as well as reduced and oxidized glutathione (GSH and GSSG, respectively) and thiobarbituric acid reactive substances (TBARS) were also assessed in brain. DOX-injected rats presented cognitive/memory impairments, increased GFAP expression, increased levels of TBARS, NO and GR, but decreased GSSG and ferritin levels in brain homogenate. In addition, increased serum and brain levels of IL-6, IL-8 and CXCL1 were noted in the DOX group, although IL-10 decreased. As DOX has a poor penetration across the blood-brain barrier (BBB), it is proposed that this drug elicits a systemic proinflammatory response with increase of proinflammatory cytokines which cross the BBB and can be involved in the induction of oxidative molecules and proinflammatory cytokines that altogether induce astrogliosis all over the brain. These events may be responsable for chemotherapy-induced cognitive/memory deficits.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Citocinas/metabolismo , Doxorrubicina/efeitos adversos , Gliose/induzido quimicamente , Inflamação/induzido quimicamente , Transtornos da Memória/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Animais , Encéfalo/imunologia , Encéfalo/metabolismo , Encéfalo/patologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Citocinas/sangue , Inflamação/imunologia , Inflamação/metabolismo , Masculino , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Transtornos da Memória/fisiopatologia , Ratos , Ratos Wistar
6.
Epilepsy Behav. ; 105: 106945, 2020.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib17469

RESUMO

The tremor mutant phenotype results from an autosomal recessive spontaneous mutation arisen in a Swiss–Webster mouse colony. The mutant mice displayed normal development until three weeks of age when they began to present motor impairment comprised by whole body tremor, ataxia, and decreased exploratory behavior. These features increased in severity with aging suggesting a neurodegenerative profile. In parallel, they showed audiogenic generalized clonic seizures. Results from genetic mapping identified the mutation tremor on chromosome 14, in an interval of 5 cM between D14Mit37 (33.21cM) and D14Mit115 (38.21cM), making Early Growth Response 3 (Egr3) the main candidate gene. Comparing with wild type (WT) mice, the tremor mice showed higher hippocampal gene expression of Egr3 and Gabra1 and increased concentrations of noradrenalin (NOR; p=.0012), serotonin (5HT; p=.0083), 5-hydroxyindoleacetic acid (5-HIAA; p=.0032), gama-amino butyric acid (GABA; p=.0123), glutamate (p=.0217) and aspartate (p=.0124). In opposition, the content of glycine (p=.0168) and the vanillylmandelic acid (VMA)/NOR ratio (p=.032) were decreased. Regarding to dopaminergic system, neither dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents nor the turnover rate of DA showed statistically significant differences between WT and mutant mice. Data demonstrated that audiogenic seizures of tremor mice are associated with progressive motor impairment as well as to hippocampal alterations of the Egr3 and Gabra1 gene expression and amino acid and monoamine content. In addition, the tremor mice could be useful for study of neurotransmission pathways as modulators of epilepsy and the pathogenesis of epilepsies occurring with generalized clonic seizures.

7.
Epilepsy Behav, v. 105, 106945, fev. 2020
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2955

RESUMO

The tremor mutant phenotype results from an autosomal recessive spontaneous mutation arisen in a Swiss–Webster mouse colony. The mutant mice displayed normal development until three weeks of age when they began to present motor impairment comprised by whole body tremor, ataxia, and decreased exploratory behavior. These features increased in severity with aging suggesting a neurodegenerative profile. In parallel, they showed audiogenic generalized clonic seizures. Results from genetic mapping identified the mutation tremor on chromosome 14, in an interval of 5 cM between D14Mit37 (33.21cM) and D14Mit115 (38.21cM), making Early Growth Response 3 (Egr3) the main candidate gene. Comparing with wild type (WT) mice, the tremor mice showed higher hippocampal gene expression of Egr3 and Gabra1 and increased concentrations of noradrenalin (NOR; p=.0012), serotonin (5HT; p=.0083), 5-hydroxyindoleacetic acid (5-HIAA; p=.0032), gama-amino butyric acid (GABA; p=.0123), glutamate (p=.0217) and aspartate (p=.0124). In opposition, the content of glycine (p=.0168) and the vanillylmandelic acid (VMA)/NOR ratio (p=.032) were decreased. Regarding to dopaminergic system, neither dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents nor the turnover rate of DA showed statistically significant differences between WT and mutant mice. Data demonstrated that audiogenic seizures of tremor mice are associated with progressive motor impairment as well as to hippocampal alterations of the Egr3 and Gabra1 gene expression and amino acid and monoamine content. In addition, the tremor mice could be useful for study of neurotransmission pathways as modulators of epilepsy and the pathogenesis of epilepsies occurring with generalized clonic seizures.

8.
Eur J Neurosci ; 50(6): 2942-2954, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30888692

RESUMO

Grooming behaviour has different functions on many species during development and can be observed and affected during periods of stress. By selecting male mice with high (HI) and low (LI) immobility traits in the tail suspension test, a screening for antidepressant drugs, we investigate how these phenotypes associated with grooming behaviour may be influenced by the effects of repeated restraint stress. For this we used the sucrose preference test and the splash test in a novel and a familiar cage performed before and after exposure to 2 days of restraint stress. Animals were submitted to an additional day of restraint stress before the hypothalamus, prefrontal cortex and midbrain extraction for dopamine activity analysis. Corticosterone analysis was made in three distinct moments: without stress (prior first restraint session), immediately after the last restrain, and 1 hr after the last restrain episode. Compared to LI group, HI animals exhibited an increased frequency and decreased time of grooming in the familiar cage. In the novel cage, stress increased frequency and time of grooming of HI animals compared to LI. Corticosterone levels were increased in HI animals after 3 days of stress. Lower hypothalamic dopaminergic activity without stress and decreased hypothalamic dopaminergic activity immediately after stress in HI group were observed. The HI group displayed decreased prefrontal cortex dopaminergic activity and increased activity in the mesolimbic area. We proposed that through the influence of stress the two phenotypes manifested as a resilient (LI) and a not resilient (HI) trait in response to restraint stress.


Assuntos
Dopamina/metabolismo , Asseio Animal/fisiologia , Resiliência Psicológica , Estresse Psicológico/metabolismo , Animais , Corticosterona/sangue , Elevação dos Membros Posteriores , Hipotálamo/metabolismo , Masculino , Mesencéfalo/metabolismo , Camundongos , Córtex Pré-Frontal/metabolismo , Restrição Física
9.
Neuroimmunomodulation ; 26(6): 285-291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31935743

RESUMO

OBJECTIVE: Previously we observed an attenuation of body temperature in lactating rats treated with lipopolysaccharide (LPS) compared with virgin saline-treated females. We proposed that high levels of prolactin (PRL) during lactation may induce this attenuation because PRL has a suppressive effect on inflammation. In the present study, we induced hyperprolactinemia in female virgin rats to investigate the effects of PRL on body temperature and sickness behavior induced by LPS. METHODS: To induce hyperprolactinemia, female rats in the estrous phase received domperidone 3 times/day for 5 days and an LPS injection (D + LPS group). Two other groups were treated with saline solution for 5 days, and one of them received a saline injection (S + S group) and the other LPS (S + LPS group). Tympanic temperature was assessed 0, 2, 4, 6, 8, 10, 24, 48, 72, and 96 h after treatment. Body weight gain and food and water consumption were observed 24, 48, 72, and 96 h after treatment. RESULTS: Hyperprolactinemia impaired LPS-induced hypothermia and hyperthermia phases of body temperature. Body weight gains in the S + LPS group and the D + LPS group were similar. A decrease in food consumption was observed in the D + LPS rats at 72 and 96 h compared to the S + LPS group. CONCLUSION: Hyperprolactinemia impaired the body temperature increase induced by LPS and several signs of sickness behavior, suggesting that febrile responses to LPS can be modulated by the physiological state. These phenomena may have adaptive value for reproduction.


Assuntos
Temperatura Corporal/efeitos dos fármacos , Hiperprolactinemia , Comportamento de Doença/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Animais , Temperatura Corporal/fisiologia , Feminino , Comportamento de Doença/fisiologia , Ratos , Ratos Wistar
10.
J Clin Invest ; 129(1): 230-245, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30352046

RESUMO

Levothyroxine (LT4) is a form of thyroid hormone used to treat hypothyroidism. In the brain, T4 is converted to the active form T3 by type 2 deiodinase (D2). Thus, it is intriguing that carriers of the Thr92Ala polymorphism in the D2 gene (DIO2) exhibit clinical improvement when liothyronine (LT3) is added to LT4 therapy. Here, we report that D2 is a cargo protein in ER Golgi intermediary compartment (ERGIC) vesicles, recycling between ER and Golgi. The Thr92-to-Ala substitution (Ala92-D2) caused ER stress and activated the unfolded protein response (UPR). Ala92-D2 accumulated in the trans-Golgi and generated less T3, which was restored by eliminating ER stress with the chemical chaperone 4-phenyl butyric acid (4-PBA). An Ala92-Dio2 polymorphism-carrying mouse exhibited UPR and hypothyroidism in distinct brain areas. The mouse refrained from physical activity, slept more, and required additional time to memorize objects. Enhancing T3 signaling in the brain with LT3 improved cognition, whereas restoring proteostasis with 4-PBA eliminated the Ala92-Dio2 phenotype. In contrast, primary hypothyroidism intensified the Ala92-Dio2 phenotype, with only partial response to LT4 therapy. Disruption of cellular proteostasis and reduced Ala92-D2 activity may explain the failure of LT4 therapy in carriers of Thr92Ala-DIO2.


Assuntos
Encéfalo , Estresse do Retículo Endoplasmático , Hipotireoidismo , Iodeto Peroxidase , Polimorfismo Genético , Resposta a Proteínas não Dobradas , Substituição de Aminoácidos , Animais , Encéfalo/enzimologia , Encéfalo/patologia , Retículo Endoplasmático/enzimologia , Retículo Endoplasmático/genética , Complexo de Golgi/enzimologia , Complexo de Golgi/genética , Células HEK293 , Humanos , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/enzimologia , Hipotireoidismo/genética , Hipotireoidismo/patologia , Iodeto Peroxidase/genética , Iodeto Peroxidase/metabolismo , Camundongos , Camundongos Transgênicos , Mutação de Sentido Incorreto , Tiroxina/uso terapêutico , Tri-Iodotironina/uso terapêutico
11.
Arch Oral Biol ; 97: 165-169, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30391792

RESUMO

The pain in dentin hypersensitivity (DH) has distinct sensory and emotional origins, with variations that occur in different intensities for each individual. The aim of this study is to evaluate the effects of diazepam in the attenuation of the pain induced by DH. DESIGN: Fifty male Wistar rats were divided into five groups: control group received water ad libitum (C); stress group received water ad libitum plus stress (S); DH induced by erosion challenge with isotonic solution ad libitum (G); DH and stress (GS); and DH, stress and diazepam (GSD) groups. Animals of the GS group were exposed to the New York Subway Stress Model. Animals treated with diazepam (GSD group) received 1 mg/kg every 3 days, from the 15th day of treatment until the end of the stress-inducing period. The body weights of rats were weekly registered. After 30 days, all groups were submitted to the DH test, which was assessed using cold water stimuli, and were graded 0, 0.5, 1, 2, or 3. Dental elements were evaluated using scanning electron microscopy (SEM). RESULTS: 1) Groups G and GS presented the highest DH scores, which confirms that stress increased pain response; 2) GSD group had significantly reduced DH scores compared to G and GS groups; 3) SEM of dental elements showed exposed dentin tubules in G, GS, and GSD groups, as expected. CONCLUSIONS: diazepam attenuated pain induced by dentin hypersensitivity in rats exposed to stress.


Assuntos
Sensibilidade da Dentina/tratamento farmacológico , Diazepam/farmacologia , Manejo da Dor/métodos , Estresse Psicológico/complicações , Animais , Dentina/ultraestrutura , Modelos Animais de Doenças , Masculino , Microscopia Eletrônica de Varredura , Ratos , Ratos Wistar , Propriedades de Superfície
12.
Nutr Neurosci ; 22(11): 805-816, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29514592

RESUMO

Objectives: Estrogen and phytoestrogens, mainly isoflavones (SIF) treatment has been suggested to improve mood, behavior, and cognitive function in postmenopausal women. However, there is a lack of information on the mechanism of such treatment on the central nervous system. We used rats to investigate the effects of long-term treatment with commercial isoflavones on behavior, hormones, and brain neurotransmitter levels. Methods: Intact female middle-aged (12 months) rats received 50, 100, and 200 mg/kg/day of commercial isoflavones extract by gavage for 90 days. After treatment, locomotor activity, anxiety-like behavior, spatial memory, estradiol, and neurotransmitter levels were measured. Results: Isoflavones treatment decreased total body weight gain in rats received 100 (P < 0.05) and 200 mg/kg (P < 0.05). There were no differences in locomotor activity or anxiety-like behavior; however, isoflavone treatment improved spatial memory (P < 0.05). Estradiol concentration was increased (P < 0.05) in groups SIF 100 and SIF 200. Glutamate (P < 0.01) and γ-aminobutyric acid (GABA) were increased in the prefrontal cortex (PFC) of rats receiving the highest doses and in the hypothalamus in rats that received SIF200 (P < 0.05). Discussion: These findings showed that long-term treatment with commercial isoflavones decreased total body weight gain and facilitated spatial memory performance in rats and this may be involved with the increase in estradiol levels as well as the increase in GABA and glutamate levels in PFC. Furthermore, isoflavones treatment may attenuate age-related cognitive impairment and may therefore be an effective tool to combat this undesirable feature of the natural aging process.


Assuntos
Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Estradiol/análise , Ácido Glutâmico/análise , Isoflavonas/administração & dosagem , Ácido gama-Aminobutírico/análise , Animais , Ansiedade/prevenção & controle , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Menopausa/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Ratos Wistar , Memória Espacial/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos
13.
Behav Brain Res ; 359: 958-966, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29913187

RESUMO

Otoconia are crucial for the correct processing of positional information and orientation. Mice lacking otoconia cannot sense the direction of the gravity vector and cannot swim properly. This study aims to characterize the behavior of mergulhador (mlh), otoconia-deficient mutant mice. Additionally, the central catecholamine levels were evaluated to investigate possible correlations between behaviors and central neurotransmitters. A sequence of behavioral tests was used to evaluate the parameters related to the general activity, sensory nervous system, psychomotor system, and autonomous nervous system, in addition to measuring the acquisition of spatial and declarative memory, anxiety-like behavior, motor coordination, and swimming behavior of the mlh mutant mice. As well, the neurotransmitter levels in the cerebellum, striatum, frontal cortex, and hippocampus were measured. Relative to BALB/c mice, the mutant mlh mice showed 1) reduced locomotor and rearing behavior, increased auricular and touch reflexes, decreased motor coordination and increased micturition; 2) decreased responses in the T-maze and aversive wooden beam tests; 3) increased time of immobility in the tail suspension test; 4) no effects in the elevated plus maze or object recognition test; 5) an inability to swim; and 6) reduced turnover of dopaminergic system in the cerebellum, striatum, and frontal cortex. Thus, in our mlh mutant mice, otoconia deficiency reduced the motor, sensory and spatial learning behaviors likely by impairing balance. We did not rule out the role of the dopaminergic system in all behavioral deficits of the mlh mutant mice.


Assuntos
Proteínas de Membrana/genética , Mutação/genética , Neurotransmissores/metabolismo , Membrana dos Otólitos/patologia , Doenças Vestibulares/genética , Animais , Comportamento Exploratório/fisiologia , Elevação dos Membros Posteriores , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Mutantes , Atividade Motora , Desempenho Psicomotor/fisiologia , Reconhecimento Psicológico/fisiologia , Aprendizagem Espacial , Natação , Doenças Vestibulares/etiologia
14.
Nutr. neurosci. ; 22(11): 805-816, 2019.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib17235

RESUMO

Objectives: Estrogen and phytoestrogens, mainly isoflavones (SIF) treatment has been suggested to improve mood, behavior, and cognitive function in postmenopausal women. However, there is a lack of information on the mechanism of such treatment on the central nervous system. We used rats to investigate the effects of long-term treatment with commercial isoflavones on behavior, hormones, and brain neurotransmitter levels. Methods: Intact female middle-aged (12 months) rats received 50, 100, and 200 mg/kg/day of commercial isoflavones extract by gavage for 90 days. After treatment, locomotor activity, anxiety-like behavior, spatial memory, estradiol, and neurotransmitter levels were measured. Results: Isoflavones treatment decreased total body weight gain in rats received 100 (P?<?0.05) and 200 mg/kg (P?<?0.05). There were no differences in locomotor activity or anxiety-like behavior; however, isoflavone treatment improved spatial memory (P?<?0.05). Estradiol concentration was increased (P?<?0.05) in groups SIF 100 and SIF 200. Glutamate (P?<?0.01) and ?-aminobutyric acid (GABA) were increased in the prefrontal cortex (PFC) of rats receiving the highest doses and in the hypothalamus in rats that received SIF200 (P?<?0.05). Discussion: These findings showed that long-term treatment with commercial isoflavones decreased total body weight gain and facilitated spatial memory performance in rats and this may be involved with the increase in estradiol levels as well as the increase in GABA and glutamate levels in PFC. Furthermore, isoflavones treatment may attenuate age-related cognitive impairment and may therefore be an effective tool to combat this undesirable feature of the natural aging process.

15.
Nutr neurosci, v. 22, n. 11, p. 805-816, mar. 2019
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2854

RESUMO

Objectives: Estrogen and phytoestrogens, mainly isoflavones (SIF) treatment has been suggested to improve mood, behavior, and cognitive function in postmenopausal women. However, there is a lack of information on the mechanism of such treatment on the central nervous system. We used rats to investigate the effects of long-term treatment with commercial isoflavones on behavior, hormones, and brain neurotransmitter levels. Methods: Intact female middle-aged (12 months) rats received 50, 100, and 200 mg/kg/day of commercial isoflavones extract by gavage for 90 days. After treatment, locomotor activity, anxiety-like behavior, spatial memory, estradiol, and neurotransmitter levels were measured. Results: Isoflavones treatment decreased total body weight gain in rats received 100 (P?<?0.05) and 200 mg/kg (P?<?0.05). There were no differences in locomotor activity or anxiety-like behavior; however, isoflavone treatment improved spatial memory (P?<?0.05). Estradiol concentration was increased (P?<?0.05) in groups SIF 100 and SIF 200. Glutamate (P?<?0.01) and ?-aminobutyric acid (GABA) were increased in the prefrontal cortex (PFC) of rats receiving the highest doses and in the hypothalamus in rats that received SIF200 (P?<?0.05). Discussion: These findings showed that long-term treatment with commercial isoflavones decreased total body weight gain and facilitated spatial memory performance in rats and this may be involved with the increase in estradiol levels as well as the increase in GABA and glutamate levels in PFC. Furthermore, isoflavones treatment may attenuate age-related cognitive impairment and may therefore be an effective tool to combat this undesirable feature of the natural aging process.

16.
Neuroimmunomodulation ; 25(2): 89-95, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30145585

RESUMO

OBJECTIVES: Previous studies from our group showed that lipopolysaccharide (LPS) exposure induces several signs of sickness behavior, including a decrease in food consumption, body weight gain, adipsia, and a biphasic effect in tympanic temperature with a first phase of hypothermia, followed by an increased tympanic temperature. LPS can activate a chain of nonspecific host responses, including the immune response, and decreased zinc levels. In addition, there are differences in the immune response between males and females, particularly fever, with sex hormones interfering with body temperature. This study aims to characterize the effects of zinc treatment on tympanic temperature, body weight gain, food and water consumption, and general activity in open field of virgin female rats exposed to a dose of LPS that was previously reported to induce sickness behavior. METHODS: Virgin female Wistar rats were treated with either saline (S) or LPS. One hour later, the S group received another injection of saline (S + S group), half of the LPS group received saline (LPS + S group) and the other half received zinc (LPS + Zn group). Tympanic temperature, body weight, and water and food consumption were measured for 96 h. Measurements and observations started 2 h after LPS administration. RESULTS: Treatment with zinc attenuated LPS-increased temperature, decreased the body weight gain and food consumption, and water consumption was increased. CONCLUSION: Zinc treatment is beneficial as it reduces the increased tympanic temperature induced by LPS, but it does not influence other sickness behavior caused by exposure to LPS.


Assuntos
Temperatura Corporal/efeitos dos fármacos , Comportamento de Doença/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Comportamento Sexual Animal , Zinco/farmacologia , Animais , Temperatura Corporal/fisiologia , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Feminino , Comportamento de Doença/fisiologia , Distribuição Aleatória , Ratos , Ratos Wistar , Comportamento Sexual Animal/efeitos dos fármacos , Comportamento Sexual Animal/fisiologia , Zinco/sangue
17.
Arq Neuropsiquiatr ; 76(4): 252-256, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29742238

RESUMO

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.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Proteína Glial Fibrilar Ácida/análise , Gliose/etiologia , Doenças Hipotalâmicas/etiologia , Xantinas/administração & dosagem , Animais , Gliose/prevenção & controle , Doenças Hipotalâmicas/prevenção & controle , Masculino , Ratos , Ratos Wistar
18.
Arq. neuropsiquiatr ; 76(4): 252-256, Apr. 2018. graf
Artigo em Inglês | LILACS | ID: biblio-888375

RESUMO

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.


Assuntos
Animais , Masculino , Ratos , Xantinas/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Proteína Glial Fibrilar Ácida/análise , Gliose/etiologia , Doenças Hipotalâmicas/etiologia , Ratos Wistar , Gliose/prevenção & controle , Doenças Hipotalâmicas/prevenção & controle
19.
Prog Neuropsychopharmacol Biol Psychiatry ; 84(Pt A): 173-180, 2018 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-29481896

RESUMO

Autism is characterized by numerous behavioral impairments, such as in communication, socialization and cognition. Recent studies have suggested that valproic acid (VPA), an anti-epileptic drug with teratogenic activity, is related to autism. In rodents, VPA exposure during pregnancy induces autistic-like effects. Exposure to VPA may alter zinc metabolism resulting in a transient deficiency of zinc. Therefore, we selected zinc as a prenatal treatment to prevent VPA-induced impairments in a rat model of autism. Wistar female rats received either saline solution or VPA (400 mg/kg, i.p) on gestational day (GD) 12.5. To test the zinc supplementation effect, after 1 h of treatment with saline or VPA, a dose of zinc (2 mg/kg, s.c.) was injected. The offspring were tested for abnormal communication behaviors with an ultrasound vocalization task on postnatal day (PND) 11, repetitive behaviors and cognitive ability with a T-maze task on PND 29, and social interaction with a play behavior task on PND 30. Tyrosine hydroxylase protein (TH) expression was evaluated in the striatum. Prenatal VPA decreased ultrasonic vocalization, induced repetitive/restricted behaviors and cognitive inflexibility, impaired socialization, and reduced striatal TH levels compared with control group. Zinc treatment reduced VPA-induced autistic-like behaviors. However, we found no evidence of an effect of zinc on the VPA-induced reduction in TH expression. The persistence of low TH expression in the VPA-Zn group suggests that Zn-induced behavioral improvement in autistic rats may not depend on TH activity.


Assuntos
Transtorno Autístico/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Efeitos Tardios da Exposição Pré-Natal , Ácido Valproico/toxicidade , Zinco/farmacologia , Animais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/crescimento & desenvolvimento , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Gravidez , Ratos Wistar , Comportamento Social , Tirosina 3-Mono-Oxigenase/metabolismo , Ultrassom , Vocalização Animal/efeitos dos fármacos
20.
Res Vet Sci ; 117: 178-186, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29288959

RESUMO

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.


Assuntos
Ivermectina/farmacologia , Espermatogênese/efeitos dos fármacos , Adulto , Animais , Humanos , Células Intersticiais do Testículo , Masculino , Ratos , Testículo , Testosterona
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