RESUMEN
Multiple sclerosis (MS) is associated with alterations in neuroendocrine function, primarily the hypothalamic-pituitary-adrenal axis, including lower expression of the glucocorticoid receptor (GR) and its target genes in peripheral blood mononuclear cells (PBMC) or full blood. We previously found reduced mineralocorticoid receptor (MR) expression in MS patients' peripheral blood. MS is being treated with a widening variety of disease-modifying treatments (DMT), some of which have similar efficacy but different mechanisms of action; body-fluid biomarkers to support the choice of the optimal initial DMT and/or to indicate an unsatisfactory response before clinical activity are unavailable. Using cell culture of volunteers' PBMCs and subsequent gene expression analysis (microarray and qPCR validation), we identified the mRNA expression of OTUD1 to represent MR signaling. The MR and MR target gene expression levels were then measured in full blood samples. In 119 MS (or CIS) patients, the expression of both MR and OTUD1 was lower than in 42 controls. The expression pattern was related to treatment, with the MR expression being particularly low in patients treated with fingolimod. While MR signaling may be involved in the therapeutic effects of some disease-modifying treatments, MR and OTUD1 expression can complement the neuroendocrine assessment of MS disease course. If confirmed, such assessment may support clinical decision-making.
Asunto(s)
Leucocitos Mononucleares , Esclerosis Múltiple , Receptores de Mineralocorticoides , Transducción de Señal , Humanos , Receptores de Mineralocorticoides/metabolismo , Receptores de Mineralocorticoides/genética , Esclerosis Múltiple/sangre , Esclerosis Múltiple/genética , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/patología , Femenino , Masculino , Adulto , Leucocitos Mononucleares/metabolismo , Persona de Mediana EdadRESUMEN
We are somewhat surprised about the extent of the feedback that we received upon our publication [...].
Asunto(s)
Teléfono Celular , Encéfalo , Ingestión de Alimentos , Homeostasis , Humanos , NutrientesRESUMEN
Obesity and mobile phone usage have simultaneously spread worldwide. Radio frequency-modulated electromagnetic fields (RF-EMFs) emitted by mobile phones are largely absorbed by the head of the user, influence cerebral glucose metabolism, and modulate neuronal excitability. Body weight adjustment, in turn, is one of the main brain functions as food intake behavior and appetite perception underlie hypothalamic regulation. Against this background, we questioned if mobile phone radiation and food intake may be related. In a single-blind, sham-controlled, randomized crossover comparison, 15 normal-weight young men (23.47 ± 0.68 years) were exposed to 25 min of RF-EMFs emitted by two different mobile phone types vs. sham radiation under fasting conditions. Spontaneous food intake was assessed by an ad libitum standard buffet test and cerebral energy homeostasis was monitored by 31phosphorus-magnetic resonance spectroscopy measurements. Exposure to both mobile phones strikingly increased overall caloric intake by 22-27% compared with the sham condition. Differential analyses of macronutrient ingestion revealed that higher calorie consumption was mainly due to enhanced carbohydrate intake. Measurements of the cerebral energy content, i.e., adenosine triphosphate and phosphocreatine ratios to inorganic phosphate, displayed an increase upon mobile phone radiation. Our results identify RF-EMFs as a potential contributing factor to overeating, which underlies the obesity epidemic. Beyond that, the observed RF-EMFs-induced alterations of the brain energy homeostasis may put our data into a broader context because a balanced brain energy homeostasis is of fundamental importance for all brain functions. Potential disturbances by electromagnetic fields may therefore exert some generalized neurobiological effects, which are not yet foreseeable.
Asunto(s)
Teléfono Celular , Ingestión de Alimentos/efectos de la radiación , Radiación Electromagnética , Metabolismo Energético/efectos de la radiación , Homeostasis/efectos de la radiación , Encéfalo/efectos de la radiación , Estudios Cruzados , Ingestión de Energía/efectos de la radiación , Humanos , Masculino , Método Simple Ciego , Adulto JovenRESUMEN
The neurotransmitter noradrenaline (NA) mediates arousal, attention and mood, and exerts anti-inflammatory and neuroprotective effects. Alterations of monoamine signalling were reported in multiple sclerosis (MS) and psychiatric illness and may account for the high prevalence of comorbid depression and fatigue in MS patients. We assessed central noradrenaline transporter (NAT) availability using positron emission tomography (PET) and the NAT selective radiotracer S,S-[11C]O-methylreboxetine in immunotherapy-naïve patients with relapsing-remitting MS (RRMS; n = 11) compared to healthy controls (HC; n = 12), and its association to lesion load, time since manifestation, the expanded disability status scale (EDSS), the fatigue scale Würzburger Erschöpfungsinventar bei MS (WEIMuS) and Beck Depression Inventory (BDI). We found NAT availability to be increased in the thalamus, amygdala, putamen and pons/midbrain of MS patients. No relation to clinical or psychometric variables was found. These first data indicate higher NAT availability in subcortical brain regions of immunotherapy-naïve RRMS patients. If these changes of noradrenergic neurotransmission predispose to psychiatric symptoms or associate with disease activity needs to be investigated in longitudinal studies or a larger sample which allows subgroup analyses.
Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Inmunoterapia , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/terapia , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismo , Adulto , Radioisótopos de Carbono/metabolismo , Depresión/psicología , Evaluación de la Discapacidad , Fatiga/psicología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Norepinefrina/metabolismo , Tomografía de Emisión de Positrones/métodos , Escalas de Valoración Psiquiátrica , Reboxetina/metabolismo , Adulto JovenRESUMEN
Pain is frequent in multiple sclerosis (MS) and includes different types, with neuropathic pain (NP) being most closely related to MS pathology. However, prevalence estimates vary largely, and causal relationships between pain and biopsychosocial factors in MS are largely unknown. Longitudinal studies might help to clarify the prevalence and determinants of pain in MS. To this end, we analyzed data from 410 patients with newly diagnosed clinically isolated syndrome or relapsing-remitting MS participating in the prospective multicenter German National MS Cohort Study (NationMS) at baseline and after 4 years. Pain was assessed by self-report using the PainDETECT Questionnaire. Neuropsychiatric assessment included tests for fatigue, depression, and cognition. In addition, sociodemographic and clinical data were obtained. Prevalence of pain of any type was 40% and 36% at baseline and after 4 years, respectively, whereas prevalence of NP was 2% and 5%. Pain of any type and NP were both strongly linked to fatigue, depression, and disability. This link was even stronger after 4 years than at baseline. Moreover, changes in pain, depression, and fatigue were highly correlated without any of these symptoms preceding the others. Taken together, pain of any type seems to be much more frequent than NP in early nonprogressive MS. Moreover, the close relationship between pain, fatigue, and depression in MS should be considered for treatment decisions and future research on a possible common pathophysiology.