RESUMO
Alzheimer disease's (AD) is a neurodegenerative disorder characterized by cognitive and behavioral impairment. The central nervous system is an important target of thyroid hormones (TH). An inverse association between serum triiodothyronine (T3) levels and the risk of AD symptoms and progression has been reported. We investigated the effects of T3 treatment on the depression-like behavior in male transgenic 3xTg-AD mice. Animals were divided into 2 groups treated with daily intraperitoneal injections of 20 ng/g of body weight (b.w.) L-T3 (T3 group) or saline (vehicle, control group). The experimental protocol lasted 21 days, and behavioral tests were conducted on days 18-20. At the end of the experiment, the TH profile and hippocampal gene expression were evaluated. The T3-treated group significantly increased serum T3 and decreased thyroxine (T4) levels. When compared to control hippocampal samples, the T3 group exhibited attenuated glycogen synthase kinase-3 (GSK3), metalloproteinase 10 (ADAM10), amyloid-beta precursor-protein (APP), serotonin transporter (SERT), 5HT1A receptor, monocarboxylate transporter 8 (MCT8) and bone morphogenetic protein 7 (BMP-7) gene expression, whereas augmented superoxide dismutase 2 (SOD2) and Hairless gene expression. T3-treated animals also displayed reduced immobility time in both the tail suspension and forced swim tests, and in the latter presented a higher latency time compared to the control group. Therefore, our findings suggest that in an AD mouse model, T3 supplementation promotes improvements in depression-like behavior, through the modulation of the serotonergic related genes involved in the transmission mediated by 5HT1A receptors and serotonin reuptake, and attenuated disease progression.
Assuntos
Doença de Alzheimer , Tri-Iodotironina , Animais , Camundongos , Masculino , Tri-Iodotironina/farmacologia , Tri-Iodotironina/uso terapêutico , Doença de Alzheimer/metabolismo , Depressão/tratamento farmacológico , Quinase 3 da Glicogênio Sintase , Camundongos Transgênicos , Hormônios Tireóideos/metabolismo , Modelos Animais de DoençasRESUMO
Pathology of the rhinencephalon has been a subject of interest in the fields of neurodegenerative diseases, trauma, epilepsy and other neurological conditions. Most of what is known about the human rhinencephalon comes from comparative anatomy studies in other mammals and histological studies in primates. Functional imaging studies can provide new and important insight into the function of the rhinencephalon in humans but have limited spatial resolution, limiting its contribution to the study of the anatomy of the human rhinencephalon. In this study we aim to provide a brief and objective review of the anatomy of this important and often overlooked area of the nervous system.
Assuntos
Córtex Olfatório/anatomia & histologia , Humanos , Ilustração Médica , Bulbo Olfatório/anatomia & histologia , Mucosa Olfatória/anatomia & histologia , Neurônios Receptores OlfatóriosRESUMO
ABSTRACT Pathology of the rhinencephalon has been a subject of interest in the fields of neurodegenerative diseases, trauma, epilepsy and other neurological conditions. Most of what is known about the human rhinencephalon comes from comparative anatomy studies in other mammals and histological studies in primates. Functional imaging studies can provide new and important insight into the function of the rhinencephalon in humans but have limited spatial resolution, limiting its contribution to the study of the anatomy of the human rhinencephalon. In this study we aim to provide a brief and objective review of the anatomy of this important and often overlooked area of the nervous system.
RESUMO As patologias do rinencéfalo tem sido assunto de interesse para os estudiosos das doenças neurodegenerativas, do traumatismo cranio-encefálico, epilepsia e outras doenças neurológicas. A maior parte do conhecimento sobre a anatomia do rinencéfalo vem de estudos de anatomia comparativa com outros mamíferos e estudos histológicos em primatas. Estudos de imagem funcional, apesar de proporcionarem informações úteis e interessantes a respeito do funcionamento do rinencéfalo em humanos, sofrem de resolução espacial limitada, e portanto contribuem de maneira restrita ao estudo dos limites das áreas anatômicas. Neste artigo buscamos proporcionar ao neurologista e neurocientista interessado uma revisão prática e objetiva da anatomia desta área importante e muitas vezes esquecida do sistema nervoso.
Assuntos
Humanos , Córtex Olfatório/anatomia & histologia , Ilustração Médica , Neurônios Receptores Olfatórios , Bulbo Olfatório/anatomia & histologia , Mucosa Olfatória/anatomia & histologiaRESUMO
Porphyrias are heme-associated metabolic disorders such as intermittent acute porphyria (IAP) and lead poisoning, where 5-aminolevulinate (ALA) accumulates. Effects of ALA on the CNS have been explained by ALA binding to GABA(A) receptors, followed by receptor lesions from oxyradicals and 4, 5-dioxovalerate (DOVA) generated from metal-catalyzed ALA oxidation by oxygen. We have characterized the effects of ALA and DOVA on GABA(A) receptor density in synaptosomes and neurons in vitro and also in brains of rats treated with ALA or succinylacetone methyl ester (SAME), a tyrosine catabolite derivative able to induce ALA accumulation. Radiolabeling assays revealed that following exposure to DOVA the concentration of synaptosomal GABAergic sites decreased by approximately 50%. Pretreatment with DOVA resulted in less GABA(A) receptor density in P19 and WERI cells and altered cell morphology. Furthermore, exposure to DOVA also induced a 5-fold increase in WERI cell mortality rate. Treatment with ALA resulted in loss of neuronal morphology and decrease of GABA(A) density in P19 neuronal cells. ALA and SAME treatment diminished the density of GABAergic receptors in the habenular complex and the parabigeminal nucleus of rat brain as studied by immunohistochemical procedures. Our results strongly suggest that ALA- and DOVA-promoted damage to GABA(A) receptors may contribute to the neurological manifestations of AIP and plumbism.
Assuntos
Ácido Aminolevulínico/toxicidade , Encéfalo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Receptores de GABA-A/efeitos dos fármacos , Sinaptossomos/efeitos dos fármacos , Valeratos/toxicidade , Ácido Aminolevulínico/metabolismo , Animais , Encéfalo/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Íons , Masculino , Neurônios/metabolismo , Porfirias/fisiopatologia , Ratos , Ratos Wistar , Receptores de GABA-A/metabolismo , Sinaptossomos/metabolismo , Valeratos/metabolismoRESUMO
Highly reactive oxyradicals and electronically excited triplet carbonyls can be generated in vitro by iron complexes and heme enzyme-catalyzed aerobic oxidation of synthetic or naturally occurring substances capable of enolization in aqueous medium. Monoenols and enamines, obtained by (alpha-methyne-carbonyl and -imine enolization, undergo dioxygen insertion and ultimately originate triplet species; e.g., isobutanal, 3-methylacetoacetone, Schiff bases. In turn, (alpha-hydroxy- and (alpha-aminocarbonyls (e.g., carbohydrates, 5-aminolevulinic acid) tautomerize to enediols and enolamines and yield oxyradicals, initiated by electron transfer to dioxygen, as polyphenols (e.g., 6-hydroxydopamine) and polyphenolamines do. Free radicals and excited species have been implicated in several normal and pathological processes. We here briefly review our contributions to this research area, emphasizing a possible in vivo prooxidant role for 5-aminolevulinic acid, the heme precursor accumulated in several porphyric disorders (e.g., lead poisoning, acut intermittent porphyria, tyrosinosis).