Bifidobacterium pseudocatenulatum CECT 7765 Ameliorates Neuroendocrine Alterations Associated with an Exaggerated Stress Response and Anhedonia in Obese Mice.

Obesity, besides being a problem of metabolic dysfunction, constitutes a risk factor for psychological disorders. Experimental models of diet-induced obesity have revealed that obese animals are prone to anxious and depressive-like behaviors. The present study aimed to evaluate whether Bifidobacterium pseudocatenulatum CECT 7765 could reverse the neurobehavioral consequences of obesity in a high-fat diet (HFD) fed mouse model via regulation of the gut-brain axis. Adult male wild-type C57BL-6 mice were fed a standard diet or HFD, supplemented with either placebo or the bifidobacterial strain for 13 weeks. Behavioral tests were performed, and immune and neuroendocrine parameters were analyzed including leptin and corticosterone and their receptors, Toll-like receptor 2 (TLR2) and neurotransmitters. We found that obese mice showed anhedonia (p < 0.050) indicative of a depressive-like behavior and an exaggerated hypothalamic-pituitary axis (HPA)-mediated stress response to acute physical (p < 0.001) and social stress (p < 0.050), but these alterations were ameliorated by B. pseudocatenulatum CECT 7765 (p < 0.050). These behavioral effects were parallel to reductions of the obesity-associated hyperleptinemia (p < 0.001) and restoration of leptin signaling (p < 0.050), along with fat mass loss (p < 0.010). B. pseudocatenulatum CECT 7765 administration also led to restoration of the obesity-induced reductions in adrenaline in the hypothalamus (p < 0.010), involved in the hypothalamic control of energy balance. Furthermore, the bifidobacterial strain reduced the obesity-induced upregulation of TLR2 protein or gene expression in the intestine (p < 0.010) and the hippocampus (p < 0.050) and restored the alterations of 5-HT levels in the hippocampus (p < 0.050), which could contribute to attenuating the obesity-associated depressive-like behavior (p < 0.050). In summary, the results indicate that B. pseudocatenulatum CECT 7765 could play a role in depressive behavior comorbid with obesity via regulation of endocrine and immune mediators of the gut-brain axis.

Bifidobacterium CECT 7765 modulates early stress-induced immune, neuroendocrine and behavioral alterations in mice.

Emerging evidence suggests that there is a window of opportunity within the early developmental period, when microbiota-based interventions could play a major role in modulating the gut-brain axis and, thereby, in preventing mood disorders. This study aims at evaluating the effects and mode of action of Bifidobacterium pseudocatenulatum CECT 7765 in a murine model of chronic stress induced by maternal separation (MS). C57Bl/6J male breast-fed pups were divided into four groups, which were subjected or not to MS and supplemented with placebo or B. pseudocatenulatum CECT7765 until postnatal period (P) 21 and followed-up until P41. Behavioral tests were performed and neuroendocrine parameters were analyzed including corticosterone, cytokine/chemokine concentrations and neurotransmitters. Microbiota was also analyzed in stools by 16S rRNA gene sequencing. B. pseudocatenulatum CECT 7765 administration attenuated some aspects of the excessive MS-induced stress response of the hypothalamic-pituitary-adrenal (HPA) axis, particularly corticosterone production at baseline and in response to subsequent acute stress in adulthood. B. pseudocatenulatum CECT 7765 also down-regulated MS-induced intestinal inflammation (reducing interferon gamma [IFN-γ]) and intestinal hypercatecholaminergic activity (reducing dopamine [DA] and adrenaline [A] concentrations) at P21. These effects have a long-term impact on the central nervous system (CNS) of adult mice since MS mice fed B. pseudocatenulatum CECT 7765 showed lower anxiety levels than placebo-fed MS mice, as well as normal neurotransmitter levels in the hypothalamus. The anti-inflammatory effect of B. pseudocatenulatum CECT 7765 seemed to be related to an improvement in glucocorticoid sensitivity in mesenteric lymph node immunocompetent cells at P21. The administration of B. pseudocatenulatum CECT 7765 to MS animals also reversed intestinal dysbiosis affecting the proportions of ten Operational Taxonomic Units (OTUs) at P21, which could partly explain the restoration of immune, neuroendocrine and behavioral alterations caused by stress in early and later life. In summary, we show that B. pseudocatenulatum CECT 7765 is able to beneficially modulate the consequences of chronic stress on the HPA response produced by MS during infancy with long-lasting effects in adulthood, via modulation of the intestinal neurotransmitter and cytokine network with short and long-term consequences in brain biochemistry and behavior.

Efectividad de la punción seca de un punto gatillo miofascial versus manipulación de codo sobre el dolor y fuerza máxima de prensión de la mano / Effectiveness of a myofascial trigger point dry needling versus elbow manipulation on pain and maximum hand grip strength

Objetivo Comparar el efecto provocado por la aplicación de manipulación de codo, punción seca o punción seca placebo sobre el umbral de dolor a la presión (UDP), la intensidad subjetiva de dolor y la fuerza de agarre en sujetos con punto gatillo miofascial (PGM) latente en la musculatura epicondílea. Material y métodos Se seleccionó a 52 participantes (26,9±7,6 años) con PGM latente en la musculatura epicondílea; 50 sujetos se integraron en el estudio controlado, doble ciego y aleatorizado. Se utilizó un algómetro para la medición de UDP, una escala analógica visual (EAV) para la intensidad subjetiva de dolor y un dinamómetro de mano para la fuerza máxima de prensión. Todo ello en 3 momentos de medición: preintervención, post-intervención y transcurridos 10 min. El análisis estadístico se realizó mediante un ANOVA mixto, p ≤ 0,05.ResultadosLos datos obtenidos mostraron un efecto significativo de la interacción grupo y tiempo para el UDP (p=0,01). Se produjo una disminución del UDP significativa (p=0,02) a los 10 min de la intervención comparado con el valor obtenido inmediatamente tras la intervención en el grupo manipulación. Para la variable del dolor medido mediante la EAV se observó un efecto significativo del factor tiempo (p=0,004).Conclusiones No se ha podido demostrar que la manipulación o la punción seca resulten superiores a la punción placebo en beneficios sobre el dolor, el UDP y la respuesta de fuerza de agarre en mano(AU)

Objective To compare the effect caused by a single application of elbow manipulation, dry needling and sham dry needling on pain and grip strength threshold (PPT) on subjects with latent myofascial trigger point (MTP) in the lateral epicondyle musculature. Material and methods A total of 52 participants (26.9±7.6 age) with latent MTP in the epicondyle musculature were enrolled. Fifty subjects were integrated in the double blind, randomized and controlled study. An algometer was used to measure PPT, Visual Analogue Scale (VAS) to measure the subjective intensity of pain and hand dynamometer to measure maximum grip strength. Three different points in time were measured: pre-intervention, post-intervention and 10minutes following the intervention. The statistical analysis was performed by a mixed ANOVA using P≤.05.ResultsStatistical analysis showed a significant effect for group per time interaction for the PPT (P=.01). Post-hoc tests showed a significant decrease of the PPT (P=.02) 10 minutes after the intervention compared to the post-intervention value for the manipulation group. Subjective pain measured by the VAS showed a significant effect for the time factor (P=.004).Conclusions It was not possible to demonstrate that manipulation or dry needling is superior to placebo puncture in benefits on pain, PPT and handgrip strength (AU)

Inhibition of adult hippocampal neurogenesis disrupts contextual learning but spares spatial working memory, long-term conditional rule retention and spatial reversal.

Neurogenesis in the adult dentate gyrus (DG) of the hippocampus has been implicated in neural plasticity and cognition but the specific functions contributed by adult-born neurons remain controversial. Here, we have explored the relationship between adult hippocampal neurogenesis and memory function using tasks which specifically require the participation of the DG. In two separate experiments several groups of rats were exposed to fractionated ionizing radiation (two sessions of 7 Gy each on consecutive days) applied either to the whole brain or focally, aiming at a region overlying the hippocampus. The immunocytochemical assays showed that the radiation significantly reduced the expression of doublecortin (DCX), a marker for immature neurons, in the dorsal DG. Ultrastructural examination of the DG region revealed disruption of progenitor cell niches several weeks after the radiation. In the first experiment, whole-brain and focal irradiation reduced DCX expression by 68% and 43%, respectively. Whole-brain and focally-irradiated rats were unimpaired compared with control rats in a matching-to-place (MTP) working memory task performed in the T-maze and in the long-term retention of the no-alternation rule. In the second experiment, focal irradiation reduced DCX expression by 36% but did not impair performance on (1) a standard non-matching-to-place (NMTP) task, (2) a more demanding NMTP task with increasingly longer within-trial delays, (3) a long-term retention test of the alternation rule and (4) a spatial reversal task. However, rats irradiated focally showed clear deficits in a "purely" contextual fear-conditioning task at short and long retention intervals. These data demonstrate that reduced adult hippocampal neurogenesis produces marked deficits in the rapid acquisition of emotionally relevant contextual information but spares spatial working memory function, the long-term retention of acquired spatial rules and the ability to flexibly modify learned spatial strategies.

Influence of massed and distributed context preexposure on contextual fear and Egr-1 expression in the basolateral amygdala.

Preexposure to the conditioning context can influence the expression of context-conditioned fear. We used behavioral and early growth response gene (egr-1) assays in rats to study the effects of massed and distributed context preexposure on context-conditioned fear. The results demonstrated that massed context preexposure impaired acquisition of contextual fear, an effect here referred to as delayed shock deficit. Spaced context preexposure produced similar inhibitory effects. Significantly, the introduction of a brief change of context prior to conditioning completely reversed the deficit induced by massed, but not by distributed, context preexposure. This reversibility was inversely related to the duration of the context shift. The acquisition of context-conditioned fear was associated with enhanced Egr-1 expression in the basolateral amygdala (BLA). No such increase was evident in animals undergoing distributed context preexposure or in those experiencing massed preexposure without change of context. Remarkably, a brief change of context prior to conditioning not only facilitated learning following massed preexposure but also elicited a significant elevation of Egr-1 protein levels in the BLA. The findings shown demonstrated that the inhibitory effects of massed and distributed context preexposure on conditioning could be dissociable both behaviorally and physiologically. We suggest that the delayed shock deficit associated with massed preexposure derives from perceptual fade-out or inattention and its reversal by a brief change of context from attentional recovery.