RESUMO
Trace elements and the relationships among them were investigated by direct chemical analysis in three basal ganglia regions in very old age individuals and age- and gender-related differences were assessed. After ordinary dissections at Nara Medical University were finished, the caudate nucleus, putamen, and globus pallidus belonging to the basal ganglia were removed from the identical cerebra of the subjects who consisted of 22 men and 23 women, ranging in age from 70 to 101 years (average age = 83.3 ± 7.5 years). After incineration with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that the Ca, P, and Mg contents increased significantly in the putamen with aging and the Mg content increased significantly in the globus pallidus with aging, but no elements increased significantly in the caudate nucleus with aging. Regarding the relationships among elements in the basal ganglia, extremely significant direct correlations were found among the Ca, P, and Mg contents in the putamen. These results suggested that slight calcification occurred in the putamen in very old age. With regard to seven elements of Ca, P, S, Mg, Zn, Fe, and Na, it was examined whether there were significant correlations among the caudate nucleus, putamen, and globus pallidus. It was found that there were extremely significant direct correlations among all of the three basal ganglia in the P content. Likewise, with regard to the Fe content, there were extremely or very significant direct correlations among all of the three basal ganglia. Regarding the gender difference in elements, it was found that the Ca content of the caudate nucleus was significantly higher in women than in men.
Assuntos
Envelhecimento , Gânglios da Base/química , Oligoelementos/análise , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cadáver , Cálcio/análise , Núcleo Caudado/química , Feminino , Globo Pálido/química , Humanos , Ferro/análise , Magnésio/análise , Masculino , Fósforo/análise , Putamen/química , Fatores Sexuais , Sódio/análise , Espectrofotometria Atômica , Enxofre/análise , Zinco/análiseRESUMO
BACKGROUND AND PURPOSE: It is well known that patients with MS tend to have abnormal iron deposition in and around the MS plaques, in the basal ganglia and the THA. In this study, we used SWI to quantify iron content in patients with MS and healthy volunteers. MATERIALS AND METHODS: Fifty-two patients with MS were recruited to assess abnormal iron content in their basal ganglia and THA structures. One hundred twenty-two healthy subjects were recruited to establish a baseline of normal iron content in deep GM structures. Each structure was separated into 2 regions: a low-iron-content region and a high-iron-content region. The average phase, the percentage area, and the total phase of the high-iron-content region were evaluated. A weighting was also assigned to each subject depending on the level of iron content and its deviation from the normal range. RESULTS: A clear separation between iron content in healthy subjects versus patients with MS was seen. For healthy subjects 13% and for patients with MS 65% showed an iron-weighting factor >3 SDs from the normal mean (P < .05). The results for those patients younger than 40 years are even more impressive. In these cases, only 1% of healthy subjects and 67% of patients with RRMS showed abnormally high iron content. CONCLUSIONS: Iron-weighting factors in the basal ganglia, THA, and the midbrain appeared to be abnormal in roughly two-thirds of patients with MS as measured by SWI.
Assuntos
Gânglios da Base/metabolismo , Ferro/metabolismo , Imageamento por Ressonância Magnética , Esclerose Múltipla/metabolismo , Esclerose Múltipla/fisiopatologia , Tálamo/metabolismo , Adolescente , Adulto , Idoso , Gânglios da Base/química , Humanos , Ferro/análise , Pessoa de Meia-Idade , Tálamo/química , Adulto JovemRESUMO
Bacopa monnieri (BM) has been used in Ayurvedic medicine as a nootropic, anxiolytic, antiepileptic and antidepressant. An n-butanol extract of the plant (nBt-ext BM) was analysed and found to contain Bacoside A (Bacoside A3, Bacopaside II and Bacopasaponin C). The effects of the BM extract were then studied on morphine-induced hyperactivity as well as dopamine and serotonin turnover in the striatum since these parameters have a role in opioid sensitivity and dependence. Mice were pretreated with saline or nBt-ext BM (5, 10 and 15 mg/kg, orally), 60 min before morphine administration and locomotor activity was subsequently recorded. Immediately after testing, striatal tissues were analysed for dopamine (DA), serotonin (5HT) and their metabolites using HPLC coupled with electrochemical detection. The results indicated that nBt-ext BM significantly (p < 0.001) decreased locomotor activity in both the saline and morphine treated groups. Additionally, nBt-ext BM significantly lowered morphine-induced dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-H1AA) upsurges in the striatum but failed to affect DA, 5-HT and their metabolites in the saline treated group. These findings suggest that nBt-ext BM has an antidopaminergic/serotonergic effect and may have potential beneficial effects in the treatment of morphine dependence.
Assuntos
Bacopa/química , Dopamina/metabolismo , Extratos Vegetais/farmacologia , Serotonina/metabolismo , Animais , Gânglios da Base/química , Gânglios da Base/efeitos dos fármacos , Feminino , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Morfina/farmacologia , Neurotransmissores/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologiaAssuntos
Corpo Estriado/fisiologia , Ácido Glutâmico/fisiologia , Animais , Gânglios da Base/química , Gânglios da Base/fisiologia , Córtex Cerebral/química , Córtex Cerebral/fisiologia , Corpo Estriado/química , Humanos , Camundongos , Vias Neurais/química , Vias Neurais/fisiologia , Tálamo/química , Tálamo/fisiologia , Proteína Vesicular 1 de Transporte de Glutamato/fisiologia , Proteína Vesicular 2 de Transporte de Glutamato/fisiologiaRESUMO
Decreased tissue levels of n-3 (omega-3) fatty acids, particularly docosahexaenoic acid (DHA), are implicated in the etiologies of non-puerperal and postpartum depression. This study examined the effects of a diet-induced loss of brain DHA content and concurrent reproductive status on dopaminergic parameters in adult female Long-Evans rats. An alpha-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 20-22% lower than those fed a control diet containing adequate alpha-linolenic acid. Decreased brain DHA produced a significant main effect of decreased density of ventral striatal D(2)-like receptors. Virgin females with decreased DHA also exhibited higher density of D(1)-like receptors in the caudate nucleus than virgin females with normal DHA. These receptor alterations are similar to those found in several rodent models of depression, and are consistent with the proposed hypodopaminergic basis for anhedonia and motivational deficits in depression.
Assuntos
Química Encefálica/fisiologia , Dieta , Ácidos Docosa-Hexaenoicos/análise , Receptores Dopaminérgicos/análise , Reprodução/fisiologia , Animais , Gânglios da Base/química , Núcleo Caudado/química , Depressão Pós-Parto/etiologia , Estradiol/sangue , Ácidos Graxos/análise , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Masculino , Paridade , Fosfolipídeos/análise , Período Pós-Parto , Gravidez , Ratos , Ratos Long-Evans , Receptores de Dopamina D1/análise , Receptores de Dopamina D2/análise , Ácido alfa-Linolênico/administração & dosagemRESUMO
AIM: In this paper, we seek to determine whether the iron deposition as seen by susceptibility weighted imaging (SWI) in the basal ganglia and thalamus of patients with multiple sclerosis is greater than the iron content measured in normal subjects (individuals unaffected by multiple sclerosis). As increased iron content may result from increased venous pressure, such information would add credence to the concept of Zamboni et al (1) that MS is caused by chronic cerebrospinal venous insufficiency. METHODS: Fourteen MS patients were recruited for this study with a mean age of 38 years ranging from 19 to 66 year-old. A velocity compensated 3D gradient echo sequence was used to generate SW images with a high sensitivity to iron content. We evaluated iron in the following structures: substantia nigra, red nucleus, globus pallidus, putamen, caudate nucleus, thalamus and pulvinar thalamus. Each structure was broken into two parts, a high iron content region and a low iron content region. The measured values were compared to previously established baseline iron content in these structures as a function of age. RESULTS: Twelve of fourteen patients had an increase in iron above normal levels and with a particular pattern of iron deposition in the medial venous drainage system that was associated with the confluence of the veins draining that structure. CONCLUSION: Iron may serve as a biomarker of venous vascular damage in multiple sclerosis. The backward iron accumulation pattern seen in the basal ganglia and thalamus of most MS patients is consistent with the hypothesis of venous hypertension.
Assuntos
Gânglios da Base/irrigação sanguínea , Gânglios da Base/química , Veias Cerebrais/patologia , Ferro/análise , Angiografia por Ressonância Magnética , Esclerose Múltipla/diagnóstico , Tálamo/irrigação sanguínea , Tálamo/química , Insuficiência Venosa/diagnóstico , Adulto , Idoso , Biomarcadores/análise , Veias Cerebrais/fisiopatologia , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Regulação para Cima , Insuficiência Venosa/metabolismo , Insuficiência Venosa/patologia , Insuficiência Venosa/fisiopatologia , Pressão Venosa , Adulto JovemRESUMO
Magnetic resonance imaging (MRI) studies have highlighted the possibility to investigate brain iron content in vivo. In this study, we combined T2* relaxometry and automatic segmentation of basal ganglia based on T1-weighted images in healthy subjects, with the aim of characterizing age related changes in volume and iron-related relaxivity values (R2*) of these structures. Thirty healthy subjects underwent MR imaging at 3 Tesla. Mean R2* values and volumes were calculated for the selected subcortical structures (pallidum, putamen, thalamus and caudate nucleus). Our results showed a correlation between R2* values and iron concentration as calculated from published post-mortem data. Furthermore, we observed a shrinkage/iron increase with a different pattern in the anatomical regions selected in this work, suggesting that the age-related changes on these MR parameters are specific to the subcortical structure considered. In particular, the putamen demonstrated a decrease of volume and an increase of iron level, with the posterior region of this structure appearing more disposed to iron deposition. Our work suggests that combining volumetry and iron estimation in MRI permits to investigate in vivo neurophysiological and neuropathological changes of basal ganglia.
Assuntos
Gânglios da Base/anatomia & histologia , Gânglios da Base/química , Ferro/análise , Tálamo/anatomia & histologia , Tálamo/química , Adulto , Envelhecimento , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Análise Multivariada , Tamanho do Órgão , Putamen/anatomia & histologia , Putamen/química , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Pentobarbital is known to affect cerebral metabolism; pentobarbital sedation is, however, frequently used for MR imaging and MR spectroscopy, especially in children. Accurate assessment of the brain metabolite levels is important, particularly in neonates with suspected brain injury. We investigated whether pentobarbital sedation has any effect on the ratios of spectral metabolites lactate, N-acetylaspartate, or choline in a group of premature neonates. MATERIALS AND METHODS: MR spectroscopy was performed in 43 premature neonates, all with normal concurrent MR imaging and normal neurodevelopmental outcome at 12 months of age. Of those neonates, 14 (33%) required pentobarbital (Nembutal 1 mg/kg) sedation during MR spectroscopy; the remaining 29 neonates did not receive any sedation. Ratios of lactate, choline, and N-acetylaspartate were calculated in the basal ganglia, thalami, and corticospinal tracts and compared between those neonates with and without sedation. RESULTS: Small amounts of brain lactate were detected in all of the premature neonates. The basal ganglia lactate/choline and lactate/N-acetylaspartate ratios were significantly lower, by 17% and 25% respectively, in the neonates with pentobarbital sedation compared with the age-matched neonates without sedation (P < .05). Sedation did not affect the lactate level in the thalami or the corticospinal tracts. The N-acetylaspartate/choline ratios were unaffected by pentobarbital sedation. CONCLUSION: Pentobarbital sedation is associated with lower lactate/choline and lactate/N-acetylaspartate ratios in the basal ganglia of premature neonates, as determined by proton MR spectroscopy. Investigators should be aware of this phenomenon for accurate interpretation of their MR spectroscopy results.
Assuntos
Química Encefálica/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Recém-Nascido Prematuro/metabolismo , Espectroscopia de Ressonância Magnética , Pentobarbital/farmacologia , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Gânglios da Base/química , Colina/análise , Humanos , Recém-Nascido , Ácido Láctico/análise , Tratos Piramidais/química , Tálamo/químicaRESUMO
BACKGROUND: On proton magnetic resonance spectroscopic imaging ((1)H MRSI), there is a decrease in cerebellar N-acetylaspartate/total creatine (NAA/tCr) in essential tremor (ET), signifying cerebellar neuronal dysfunction or degeneration. Harmane, which is present in the human diet, is a potent tremor-producing neurotoxin. Blood harmane concentrations seem to be elevated in ET. OBJECTIVES: To assess in patients with ET whether blood harmane concentration is correlated with cerebellar NAA/tCR, a neuroimaging measure of neuronal dysfunction or degeneration. METHODS: Twelve patients with ET underwent (1)H MRSI. The major neuroanatomic structure of interest was the cerebellar cortex. Secondary regions were the central cerebellar white matter, cerebellar vermis, thalamus, and basal ganglia. Blood concentrations of harmane and another neurotoxin, lead, were also assessed. RESULTS: Mean +/- SD cerebellar NAA/tCR was 1.52 +/- 0.41. In a linear regression model that adjusted for age and gender, log blood harmane concentration was a predictor of cerebellar NAA/tCR (beta = -0.41, p = 0.009); every 1 g(-10)/mL unit increase in log blood harmane concentration was associated with a 0.41 unit decrease in cerebellar NAA/tCR. The association between blood harmane concentration and brain NAA/tCR only occurred in the cerebellar cortex; it was not observed in secondary brain regions of interest. Furthermore, the association was specific to harmane and not another neurotoxin, lead. CONCLUSION: This study provides additional support for the emerging link between harmane, a neurotoxin, and ET. Further studies are warranted to address whether cerebellar harmane concentrations are associated with cerebellar pathology in postmortem studies of the ET brain.
Assuntos
Córtex Cerebelar/metabolismo , Tremor Essencial/sangue , Harmina/análogos & derivados , Neurotoxinas/sangue , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Gânglios da Base/química , Córtex Cerebelar/química , Cerebelo/química , Creatina/análise , Feminino , Harmina/efeitos adversos , Harmina/sangue , Humanos , Chumbo/sangue , Masculino , Ressonância Magnética Nuclear Biomolecular , Projetos Piloto , Método Simples-Cego , Tálamo/química , Gravação de VideoteipeRESUMO
OBJECTIVE: Proton magnetic resonance spectroscopy (1H-MRS) showed decreased neuronal marker N-acetylaspartate and increased glial marker myo-inositol in subjects with chronic methamphetamine use and in subjects infected with HIV. The authors sought to determine whether HIV and a history of chronic methamphetamine use might have additive or interactive effects on brain metabolite abnormalities. METHOD: 1H-MRS was performed in 68 HIV-positive subjects (24 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 2,167 g [SD=2,788] and last use a mean of 4.9 months earlier [SD=6.0]; 44 with no history of drug abuse) and 75 HIV-negative subjects (36 with a history of chronic methamphetamine use with a lifetime exposure of a mean of 8,241 g [SD=16,850] and last use a mean of 6.3 months earlier [SD=7.8]; 39 with no history of drug abuse). Concentrations of N-acetylaspartate, creatine, choline, and myo-inositol were measured in the frontal cortex, frontal white matter, and basal ganglia. RESULTS: HIV-negative subjects with a history of chronic methamphetamine use showed lower concentrations of the neuronal marker N-acetylaspartate in the frontal white matter and basal ganglia and higher concentrations of choline compounds and the glial marker myo-inositol in the frontal cortex, relative to subjects with no history of drug abuse. HIV-positive status was associated with lower concentrations of N-acetylaspartate and creatine in the frontal cortex and higher concentrations of myo-inositol in the white matter, compared with HIV-negative status. Compared to the mean concentrations of metabolites in HIV-negative subjects with no history of drug abuse, the mean concentrations in subjects with HIV and chronic methamphetamine use showed additive effects on N-acetylaspartate in all three regions (-9% in the basal ganglia, -7% in the frontal white matter, and -6% in the frontal gray matter), on creatine in the basal ganglia (-7%), and on myo-inositol in the frontal white matter (+11%). CONCLUSIONS: The combined effects of HIV and chronic methamphetamine use were consistent with an additive model, suggesting additional neuronal injury and glial activation due to the comorbid conditions.
Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Ácido Aspártico/análogos & derivados , Encefalopatias/diagnóstico , Encéfalo/metabolismo , Soropositividade para HIV/metabolismo , Espectroscopia de Ressonância Magnética/estatística & dados numéricos , Metanfetamina/efeitos adversos , Adulto , Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Ácido Aspártico/análise , Gânglios da Base/química , Encefalopatias/metabolismo , Colina/análise , Doença Crônica , Comorbidade , Creatina/análise , Feminino , Lobo Frontal/química , Soronegatividade para HIV , Soropositividade para HIV/diagnóstico , Soropositividade para HIV/epidemiologia , Humanos , Inositol/análise , MasculinoRESUMO
The authors have previously reported that intracellular pH measured by phosphorus-31 magnetic resonance spectroscopy (31P-MRS) was decreased in the frontal lobes of patients with bipolar disorder. In the present study, phosphorus metabolism in the basal ganglia was examined in 13 patients with bipolar disorder and 10 matched controls by localized 31P-MRS. While no significant alteration of peak area ratios was found for all phosphorus metabolites, intracellular pH was significantly reduced in the basal ganglia in patients with bipolar disorder (7.014 +/- 0.045) compared with control subjects (7.066 +/- 0.047, P < 0.05). Unexpectedly, non-localized 31P-MR spectra also showed significantly lower levels of intracellular pH (6.970 +/- 0.025) than controls (6.986 +/- 0.024, P < 0.05). These results suggest that decreased intracellular pH in the brain of patients with bipolar disorder is not caused by dysfunction of the frontal lobes but reflect altered metabolism at the cellular level.
Assuntos
Gânglios da Base/química , Gânglios da Base/fisiologia , Transtorno Bipolar/fisiopatologia , Fósforo/metabolismo , Adulto , Gânglios da Base/citologia , Estudos de Casos e Controles , Feminino , Humanos , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Isótopos de FósforoRESUMO
Few chemokines are expressed constitutively in the brain at detectable levels; amongst them is fractalkine. We analyzed the distribution of fractalkine in the mouse brain with the aim of giving a neuroanatomical support to the study of its physiological function. To this end, we carried out an analysis of fractalkine protein localization and gene expression. An anti-fractalkine antibody was produced and used to perform an immunohistochemical study. The results indicated a high level of fractalkine protein in cortex, hippocampus, basal ganglia, and olfactory bulb. In particular, the presence of abundant immunoreactive neurons was observed in layers II, III, V, and VI of the cortex. In the hippocampus, the CA1 region was the most intensely labeled, but immunoreactive neurons were present also in CA2 and CA3, whereas in the basal ganglia, immunoreactive cells were observed in the caudate putamen. Other brain structures such as the brainstem showed a few scattered immunoreactive cells. The presence of fractalkine immunoreactive fibers was revealed only in the olfactory bulb and in the anterior olfactory nuclei. Gene expression study results, obtained by both semiquantitative PCR and in situ hybridization, matched protein localization with the highest levels of fractalkine transcript detected in the hippocampus, cortex, and striatum. The present study showed that fractalkine protein and mRNA are constitutively expressed at a high level in forebrain structure, but are almost absent in the hindbrain. Furthermore, localization at the cellular body level would suggest a paracrine or cell-to-cell interaction role for fractalkine more than a neurotransmission modulatory function.
Assuntos
Química Encefálica , Quimiocinas CX3C/análise , Quimiocinas CX3C/genética , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Tonsila do Cerebelo/química , Tonsila do Cerebelo/fisiologia , Animais , Animais não Endogâmicos , Gânglios da Base/química , Gânglios da Base/fisiologia , Córtex Cerebral/química , Córtex Cerebral/fisiologia , Quimiocina CX3CL1 , Expressão Gênica , Hipocampo/química , Hipocampo/fisiologia , Hipotálamo/química , Hipotálamo/fisiologia , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Bulbo Olfatório/química , Bulbo Olfatório/fisiologia , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tálamo/química , Tálamo/fisiologiaRESUMO
OBJECT: In the authors' previous studies they found that brain iron accumulation and oxidative stress contribute to secondary brain damage after intracerebral hemorrhage (ICH). In the present study they investigated whether deferoxamine, an iron chelator, can reduce ICH-induced brain injury. METHODS: Male Sprague-Dawley rats received an infusion of 100 microl of autologous whole blood into the right basal ganglia and were killed 1, 3, or 7 days thereafter. Iron distribution was examined histochemically (enhanced Perl reaction). The effects of deferoxamine on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1), a repair mechanism for DNA oxidative damage, was quantitated by Western blot analysis. Iron accumulation was observed in the perihematoma zone beginning 1 day after ICH. Deferoxamine attenuated brain edema, neurological deficits, and ICH-induced changes in APE/Ref-1. CONCLUSIONS: Deferoxamine and other iron chelators may be potential therapeutic agents for treating ICH. They may act by reducing the oxidative stress caused by the release of iron from the hematoma.
Assuntos
Edema Encefálico/tratamento farmacológico , Hemorragia Cerebral/tratamento farmacológico , Terapia por Quelação , Desferroxamina/uso terapêutico , Quelantes de Ferro/uso terapêutico , Animais , Gânglios da Base/química , Edema Encefálico/etiologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/metabolismo , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/análise , Desferroxamina/farmacologia , Avaliação de Medicamentos , Hematoma/complicações , Hematoma/tratamento farmacológico , Hematoma/metabolismo , Ferro/análise , Quelantes de Ferro/farmacologia , Masculino , Proteínas do Tecido Nervoso/análise , Estresse Oxidativo , Ratos , Ratos Sprague-DawleyRESUMO
Measurements of serotonin (5-HT), dopamine (DA), and noradrenaline, and of 5-HT and DA metabolites, were obtained by HPLC from 16 brain regions and the spinal cord of 5-HT(1A) or 5-HT(1B) knockout and wild-type mice of the 129/Sv strain. In 5-HT(1A) knockouts, 5-HT concentrations were unchanged throughout, but levels of 5-HT metabolites were higher than those of the wild type in dorsal/medial raphe nuclei, olfactory bulb, substantia nigra, and locus coeruleus. This was taken as an indication of increased 5-HT turnover, reflecting an augmented basal activity of midbrain raphe neurons and consequent increase in their somatodendritic and axon terminal release of 5-HT. It provided a likely explanation for the increased anxious-like behavior observed in 5-HT(1A) knockout mice. Concomitant increases in DA content and/or DA turnover were interpreted as the result of a disinhibition of DA, whereas increases in noradrenaline concentration in some territories of projection of the locus coeruleus could reflect a diminished activity of its neurons. In 5-HT(1B) knockouts, 5-HT concentrations were lower than those of the wild type in nucleus accumbens, locus coeruleus, spinal cord, and probably also several other territories of 5-HT innervation. A decrease in DA, associated with increased DA turnover, was measured in nucleus accumbens. These changes in 5-HT and DA metabolism were consistent with the increased aggressiveness and the supersensitivity to cocaine reported in 5-HT(1B) knockout mice. Thus, markedly different alterations in CNS monoamine metabolism may contribute to the opposite behavioral phenotypes of these two knockouts.
Assuntos
Sistema Nervoso Central/metabolismo , Dopamina/análogos & derivados , Dopamina/metabolismo , Receptores de Serotonina/genética , Serotonina/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/análise , Animais , Autorradiografia , Gânglios da Base/química , Gânglios da Base/metabolismo , Sistema Nervoso Central/química , Cerebelo/química , Cerebelo/metabolismo , Córtex Cerebral/química , Córtex Cerebral/metabolismo , Cromatografia Líquida de Alta Pressão , Dopamina/análise , Feminino , Ácido Homovanílico/análise , Ácido Hidroxi-Indolacético/análise , Hidroxitriptofol/análise , Hipotálamo/química , Hipotálamo/metabolismo , Masculino , Mesencéfalo/química , Mesencéfalo/metabolismo , Camundongos , Camundongos Knockout , Norepinefrina/análise , Bulbo Olfatório/química , Bulbo Olfatório/metabolismo , Especificidade de Órgãos , Receptor 5-HT1B de Serotonina , Receptores de Serotonina/deficiência , Receptores 5-HT1 de Serotonina , Serotonina/análise , Medula Espinal/química , Medula Espinal/metabolismoRESUMO
Members of the p160 family of steroid receptor coactivator proteins mediate the stimulatory effects on gene transcription brought about by nuclear receptors, which comprise all steroid receptors. Using in situ hybridization we have examined the neuroanatomical distribution of the messenger RNAs (mRNAs) for two functionally distinct splice variants of Steroid Receptor Coactivator 1 (SRC-1/NCoA-1) and of Steroid Receptor Coactivator 2 (SRC-2/NCoA-2/GRIP-1/TIF-2). Transcripts encoding these coactivators show highly differential expression patterns. SRC-2 mRNA is expressed at very low levels in brain, but shows expression in the anterior pituitary. SRC-la and le mRNA are expressed in many brain areas, including hippocampus, amygdala, hypothalamus, basal ganglia, and isocortex. Striking differences between SRC-1a and le expression were observed in several brain nuclei. Relative levels of SRC-1a mRNA were much higher in anterior pituitary, and the arcuate, paraventricular and ventromedial nucleus of the hypothalamus, the locus coeruleus and the trigeminal motor nucleus, all important targets of steroid hormones in the brain. SRC-le mRNA showed modest elevation of relative expression in the caudal nucleus accumbens (shell), basolateral amygdala, and some thalamic nuclei. The differential and uneven neuroanatomical distribution of these coactivators may underlie diversity and cell-specificity of steroid receptor mediated signals in the brain.
Assuntos
Química Encefálica , Expressão Gênica , Hipófise/química , Fatores de Transcrição/genética , Tonsila do Cerebelo/química , Animais , Gânglios da Base/química , Sequência de Bases , Encéfalo/metabolismo , Córtex Cerebral/química , Hipocampo/química , Histona Acetiltransferases , Hipotálamo/química , Hibridização In Situ , Masculino , Coativador 1 de Receptor Nuclear , Coativador 2 de Receptor Nuclear , Sondas de Oligonucleotídeos , Hipófise/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/química , Ratos , Ratos Wistar , Distribuição TecidualRESUMO
Severe autonomic dysfunction occurs in Rett syndrome (RS). Substance P, a tachykinin peptide that localizes to several brain regions, including the autonomic nervous system, is reduced in the cerebrospinal fluid of patients with RS. The anatomic localization and intensity of substance P immunoreactivity and glial fibrillary acidic protein-positive astrocytes in the brains of 14 patients with RS were compared with those in the brains of 10 age-matched normal patients. Substance P immunoreactivity expression was significantly decreased in RS tissue compared with control tissue in the following regions: dorsal horns, intermediolateral column of the spinal cord, spinal trigeminal tract, solitary tract and nucleus, parvocellular and pontine reticular nuclei, and locus ceruleus. A less significant decrease of substance P immunoreactivity occurred in the substantia nigra, central gray of the midbrain, frontal cortex, caudate, putamen, globus pallidus, and thalamus. Antiglial fibrillary acidic protein-positive astrocytes were increased in the areas in which substance P immunoreactivity was decreased and in other brain regions. Because many of the brain regions with the greatest decrease in substance P immunoreactivity are involved in the control of the autonomic nervous system, especially the solitary tracts and reticular formation, reduced substance P may contribute to the autonomic dysfunction in RS.
Assuntos
Química Encefálica , Encéfalo/patologia , Síndrome de Rett/patologia , Substância P/análise , Adolescente , Adulto , Fatores Etários , Anticorpos , Astrócitos/química , Astrócitos/patologia , Gânglios da Base/química , Gânglios da Base/patologia , Tronco Encefálico/química , Tronco Encefálico/patologia , Criança , Feminino , Lobo Frontal/química , Lobo Frontal/patologia , Proteína Glial Fibrilar Ácida/análise , Proteína Glial Fibrilar Ácida/imunologia , Hipocampo/química , Hipocampo/patologia , Humanos , Mesencéfalo/química , Mesencéfalo/patologia , Neurônios/química , Neurônios/patologia , Substância P/imunologia , Tálamo/química , Tálamo/patologiaRESUMO
Newborn mice were administered Fe(2+) (iron succinate: 7.5 mg/kg, b. wt) on either Days 3-5, 10-12 or 19-21, or vehicle (saline) at the same times, postnatally. Spontaneous motor behaviour and radial arm maze learning were tested at the age of 3 months. It was found that mice treated with Fe(2+) during postnatal Days 10-12 were markedly hypokinetic during the 1st 20-min test period and hyperkinetic during the 3rd and final 20-min test period. These mice showed an almost complete lack of habituation of spontaneous motor activity parameters to the test chambers. In the radial arm maze, the Days 10-12 treatment group evidenced significantly both more errors in arm choices and longer latencies to acquire all eight pellets; these mice showed also a severe trial-to-trial retention deficit as indexed by retention quotients. These behavioural deficits were observed also in animals treated with Fe(2+) during postnatal Days 3-5, but the effects were less pronounced, indicating the higher susceptibility of the brain for Fe(2+)-induced damage during Days 10-12 postpartum. Treatment with Fe(2+) on Days 19-21 did not induce behavioural alterations in comparison with its respective control (vehicle) group. Analysis of total brain iron content indicated significantly more iron (microg/g) accumulation in the basal ganglia, but not frontal cortex, of mice from the Days 3-5 and 10-12 Fe(2+) (7.5 mg/kg) treatment groups. The contribution of iron overload during the immediate postnatal to later functional deficits seems to implicate symptoms of Parkinsonism but the kinetics of iron uptake to the brain and its regional distribution at this critical period of development awaits elucidation.
Assuntos
Sobrecarga de Ferro/complicações , Ferro/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos Endogâmicos/metabolismo , Atividade Motora/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Gânglios da Base/química , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Feminino , Compostos Ferrosos , Lobo Frontal/química , Habituação Psicofisiológica/efeitos dos fármacos , Hipercinese/induzido quimicamente , Hipocinesia/induzido quimicamente , Ferro/análise , Sobrecarga de Ferro/induzido quimicamente , Masculino , Transtornos da Memória/induzido quimicamente , Camundongos , Tempo de Reação/efeitos dos fármacosRESUMO
The mouse "Purkinje cell degeneration" (pcd) is characterized by a primary loss of Purkinje cells, as well as by retrograde and secondary partial degeneration of cerebellar granule cells and inferior olivary neurons; this neurological mutant can be considered as an animal model of human degenerative ataxia. To determine the consequences of this cerebellar pathology on the noradrenergic system, noradrenaline transporters as well as alpha1-, alpha2- and beta-adrenergic receptors were evaluated by quantitative ligand binding autoradiography in adult control and pcd mice using, respectively, [3H]nisoxetine, [3H]prazosin, [3H]idazoxan and [3H]CGP12177. In cerebellar cortex and deep nuclei of pcd mutants, [3H]nisoxetine labelling of noradrenaline transporters was higher than in control mice. However, when binding densities were corrected by surface area, they remained unchanged in the cerebellar cortex but associated with 25% and 40% lower levels of labelling of alpha1 and beta receptors, as well as a very important increase (275%) of alpha2 receptors. In deep cerebellar nuclei, surface corrections did not reveal any changes either in transporter or in receptor densities. Higher densities of [3H]nisoxetine labelling were found in several regions related with the cerebellum, namely inferior olive, inferior colliculus, vestibular, reticular, pontine, raphe and red nuclei, as well as in primary motor and sensory cerebral cortex; they may reflect an increased noradrenergic innervation related to motor adjustments for the cerebellar dysfunction. Increased [3H]nisoxetine labelling was also measured in vegetative brainstem regions and in dorsal hypothalamus, implying altered autonomic functions and possible compensation in pcd mutants. Other changes found in extracerebellar regions affected by the mutation, such as thalamus and the olfactory system implicated both noradrenaline transporters and adrenergic receptors. In contrast to the important alterations of the noradrenergic system in cerebellar cortex, the lack of receptor changes in deep cerebellar nuclei suggests that local adaptations may be sufficient to minimize the consequence of the cerebellar atrophy on motor control. An intense labelling by [3H]idazoxan of the inner third of the molecular layer was a novel, albeit unexplained finding, and could represent a postsynaptic subset of alpha2-adrenergic receptors.
Assuntos
Norepinefrina/análise , Norepinefrina/metabolismo , Receptores Adrenérgicos/análise , Receptores Adrenérgicos/metabolismo , Degenerações Espinocerebelares/metabolismo , Antagonistas Adrenérgicos alfa/metabolismo , Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/metabolismo , Antagonistas Adrenérgicos beta/farmacologia , Animais , Autorradiografia , Gânglios da Base/química , Tronco Encefálico/química , Córtex Cerebral/química , Modelos Animais de Doenças , Feminino , Fluoxetina/análogos & derivados , Fluoxetina/metabolismo , Fluoxetina/farmacologia , Hipotálamo/química , Idazoxano/metabolismo , Idazoxano/farmacologia , Sistema Límbico/química , Camundongos , Camundongos Mutantes Neurológicos , Norepinefrina/antagonistas & inibidores , Prazosina/metabolismo , Prazosina/farmacologia , Propanolaminas/metabolismo , Propanolaminas/farmacologia , Células de Purkinje/química , Células de Purkinje/metabolismo , Ensaio Radioligante , Receptores Adrenérgicos alfa 1/análise , Receptores Adrenérgicos alfa 1/metabolismo , Receptores Adrenérgicos alfa 2/análise , Receptores Adrenérgicos alfa 2/metabolismo , Receptores Adrenérgicos beta/análise , Receptores Adrenérgicos beta/metabolismo , Degenerações Espinocerebelares/genética , Tálamo/química , TrítioRESUMO
The regional and cellular distribution of serotonin type 2C receptor messenger RNA was investigated in autopsy samples of human brain by in situ hybridization histochemistry. The main sites of serotonin receptor type 2C messenger RNA expression were the choroid plexus, cerebral cortex, hippocampus, amygdala, some components of the basal ganglia, the substantia nigra, the substantia innominata and the ventromedial hypothalamus, suggesting that this receptor might be involved in the regulation of different brain functions. Interestingly, in all regions examined, the serotonin type 2C receptor messenger RNA was always restricted to subpopulations of cells, suggesting a specific role, perhaps determined by regionality. A comparison of the in situ hybridization results with those previously obtained by means of radioligand binding experiments suggested that in most of the areas analysed the serotonin type 2C receptors were located at axon terminals.