RESUMO
Ileocolonic aganglionosis (ICA) is the congenital and hereditary absence of neurons that constitute the enteric nervous system and has been described in various species including humans - Hirschsprung's disease - and horses - overo lethal white syndrome (OLWS). Hirschsprung's disease affects circa 1 in 5,000 live births. At best, this disease means an inability to absorb nutrients from food (humans). At worse, in horses, it always means death. Despite our general understanding of the functional mechanisms underlying ICA, there is a paucity of reliable quantitative information about the structure of myenteric and submucosal neurons in healthy horses and there are no studies on horses with ICA. In light of these uncertainties, we have used design-based stereology to describe the 3-D structure - total number and true size - of myenteric and submucosal neurons in the ileum of ICA horses. Our study has shown that ICA affects all submucosal neurons and 99% of myenteric neurons. The remaining myenteric neurons (0.56%) atrophy immensely, i.e. 63.8%. We believe this study forms the basis for further research, assessing which subpopulation of myenteric neurons are affected by ileocolonic aganglionosis, and we would like to propose a new nomenclature to distinguish between a complete absence of neurons - aganglionosis - and a weaker form of the disease which we suggest naming 'hypoganglionosis'. Our results are a step forward in understanding this disease structurally.
Assuntos
Doença de Hirschsprung/veterinária , Doenças dos Cavalos/diagnóstico , Imageamento Tridimensional/métodos , Animais , Contagem de Células , Gânglios/patologia , Doença de Hirschsprung/diagnóstico , Doença de Hirschsprung/genética , Doenças dos Cavalos/genética , Cavalos , Íleo/patologia , Masculino , Neurônios/patologia , Tamanho do ÓrgãoRESUMO
Parkinson's disease (PD) is an age-related neurodegenerative disorder that severely affects quality of life of patients and their families. The flavonoid chrysin (5,7-dihydroxylflavone) is a naturally occurring flavone with several pharmacological activities, including anti-inflammatory and anti-oxidative. We investigated the effects of a 28-day chrysin treatment (10 mg/kg/day, i.g.) on a model of PD induced by 6-OHDA in aged (20-month old) mice. We found a protective effect of chrysin on behavioral and cognitive alterations (rotational behavior, passive avoidance and Barnes maze tests), nitric oxide synthesis (NOx), lipid peroxidation (HNE), glutathione levels (GSH), reactive species levels (RS), neuroinflammation (interleukin-1 beta - IL-1ß and tumor necrosis factor alpha - TNF-α), Na+, K+-ATPase and nicotinamide adenine dinucleotide phosphate oxidase activity (NADPH oxidase) activities. In addition, chrysin protected against changes in striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. In conclusion, chrysin improved several behavioral, cognitive and neurochemical parameters in a relevant preclinical model of PD in aged mice.
Assuntos
Encéfalo/efeitos dos fármacos , Cognição/efeitos dos fármacos , Flavonoides/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson Secundária/tratamento farmacológico , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Animais , Encéfalo/metabolismo , Dopamina/metabolismo , Feminino , Flavonoides/farmacologia , Ácido Homovanílico/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxidopamina , Doença de Parkinson Secundária/metabolismo , Doença de Parkinson Secundária/psicologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Chrysin is a natural flavonoid which is found in bee propolis, honey and various plants, and neuroprotective effect of chrysin in mice was previously demonstrated by our group. Neuroinflammation, neurotrophic factors and neuronal recovery factors associated with the neuroprotective effect of this flavonoid require further investigations. Thus, now we investigated the possible involvement of inflammatory cytokines, neurotrophic factors and neuronal recovery in the effect of chrysin in 6-hydroxidopamine (6-OHDA), a well-established model of Parkinson's disease, in striatum of mice. The 6-OHDA microinjection induced behavioral alterations on the rotarod test and apomorphine-induced circling behavior in mice. 6-OHDA administration elevated levels of tumour necrosis factor-α, interferon-gamma, interleukin-1ß, interleukin-2, interleukin-6 and nuclear factor-kappa B and decreased the interleukin-10 levels, total reactive antioxidant potential and total antioxidant reactivity in striatum, as well as, modified the calcium-binding protein B (S100B), brain-derived neurotrophic factor, nerve growth factor and glial cell line-derived neurotrophic factor levels. The intrastriatal injection of 6-OHDA also induced an decrease of dopamine, 3,4-dihydroxyphenylacetic acid, homovanylic acid levels and tyrosine hydroxylase content. Oral treatment with chrysin (10 mg/kg, 28 days), culminated with the prevention of these alterations occasioned by 6-OHDA. These results corroborated with the neuroprotective effect of chrysin in the treatment of Parkinson's disease and, indicated the mechanism involved throught the inflammatory cytokines, neurotrophic factors and recovery of dopaminergic neurons in striatum.