RESUMO
Cumulative evidence indicates that estrogen receptor (ER) agonists attenuate neuroinflammation. Equol, a major isoflavone from soybean, exhibits estrogen-like biological activity, but their effect on inflammatory response has not been well established. Here, we investigated the effect of S-equol on nitric oxide (NO) production, well-known inflammatory change in astrocytes stimulated by LPS. S-Equol attenuated LPS-induced NO production with a concomitant decrease in expression of inducible NO synthase (iNOS). S-Equol did not affect LPS-induced increase in intracellular ROS production. Intracellular ER blocker ICI 182.780 had no effect on S-equol-induced decrease in NO production. Addition of G-15, antagonist of G protein-coupled receptor 30 which is nongenomic ER and located on cell surface, partially recovered S-equol-induced attenuation of NO production. These findings suggest that attenuation of NO production by S-equol may mitigate LPS-induced neuroinflammation in astrocytes. S-Equol may exert a glioprotective effect, at least in part, via a nongenomic effect.
RESUMO
A male Japanese domestic cat developed progressive limb paralysis from 4 months of age. The cat showed visual disorder, trismus and cognitive impairment and died at 9 months of age. At necropsy, significant discoloration of the white matter was observed throughout the brain and spinal cord. Histologically, severe myelin loss and gliosis were observed, especially in the internal capsule and cerebellum.In the lesions, severe infiltration of macrophages with broad cytoplasm filled with PAS-positive and nonmetachromatic granules (globoid cells) was evident. On the basis of these findings, the case was diagnosed as feline globoid cell leukodystrophy (Krabbe's disease). Immunohistochemical observation indicated the involvement of oxidative stress and small HSP in the disease.
Assuntos
Doenças do Gato/patologia , Leucodistrofia de Células Globoides/patologia , Leucodistrofia de Células Globoides/veterinária , Animais , Plexo Braquial/patologia , Encéfalo/patologia , Gatos , Imuno-Histoquímica , Macrófagos/patologia , Masculino , Bainha de Mielina/patologia , Medula Espinal/patologiaRESUMO
Elucidation of the functions of astrocytes is important for understanding of the pathogenic mechanism of various neurodegenerative diseases. Theophylline is a common drug for bronchial asthma and occasionally develops side-effects, such as acute encephalopathy; although the pathogenic mechanism of the side-effects is unknown. The lipopolysaccharide (LPS)-induced nitricoxide (NO) production is generally used for an index of the activation of astrocyte in vitro. In this study, in order to elucidate the effect of theophylline on the astrocytic functions, we examined the LPS-induced NO production and the expression of iNOS in cultured rat cortex astrocytes.Theophylline alone could not induce the NO production; however, NO production induced by LPS was enhanced by theophylline in a dose-dependent manner; and by isobutylmethylxanthine, a phosphodiesterase inhibitor. The theophylline enhancement of LPS-induced NO production was further increased by dibutyryl cyclic AMP, a membrane-permeable cAMP analog; and by forskolin, an adenylate cyclase activator. When the cells were preincubated with Rp-8-Br-cAMP, an inhibitor of protein kinase A, the theophylline enhancement of LPS-induced NO production was decreased. The extent of iNOS protein expression induced by LPS was also enhanced by theophylline.It is likely that phosphodiesterase inhibition is a major action mechanism for the theophylline enhancement of LPS-induced NO production in astrocytes. Theophylline-induced acute encephalopathy might be due to the hyper-activation of astrocytes via cAMP signaling to produce excess amount of NO.
Assuntos
Astrócitos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico/biossíntese , Teofilina/farmacologia , 8-Bromo Monofosfato de Adenosina Cíclica/análogos & derivados , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Animais , Astrócitos/metabolismo , Bucladesina/farmacologia , Células Cultivadas , Colforsina/farmacologia , AMP Cíclico/fisiologia , Proteínas Quinases Dependentes de AMP Cíclico/antagonistas & inibidores , Sinergismo Farmacológico , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Ratos , Tionucleotídeos/farmacologiaRESUMO
Canine polyneuropathy is a neurological disorder characterized by a dysfunction of multiple peripheral nerves. The etiology of the disease is diverse; it may occur in cases of infectious, immune-mediated, or hereditary conditions or in association with endocrinopathy, neoplasm, or chemical intoxication. It is often difficult to determine the etiology through clinical symptoms. The aim of this study is to investigate pathological differences among three canine polyneuropathy cases with each presumably having a different etiology. Cases included a 13-month-old female border collie (Dog No.1), a 21-month-old male chihuahua (Dog No.2) and an 11-year-old male beagle (Dog No.3). Clinical examinations revealed hindlimb ataxia and sensory loss in Dog No.1, forelimb paralysis and vertebral pain in Dog No.2, and paddling-gait and hypothyroidism in Dog No.3. Histopathologically, axonal swelling and pale myelin were observed in Dog No.1. Giant axons mimicking giant axonal neuropathy were obvious in Dog No.2. Dog No.3 showed atrophic axons and severe interstitial edema. Distributions of peripheral nerve lesions coincided with respective clinical symptoms. According to their clinical and pathological features, Dogs No.1 and No.2 were suspected of hereditary polyneuropathy, while Dog No.3 seemed to have hypothyroidism-associated polyneuropathy. As each case demonstrated unique pathological features, different pathogeneses of peripheral nerve dysfunction were suggested.