Erythropoietin Inhibits Basal and Stimulated Corticotropin-Releasing Hormone Release from the Rat Hypothalamus via a Nontranscriptional Mechanism

Brain hypoxia-ischemia induces a local increase in the levels of erythropoietin (EPO) and vascular endothelial growth factor (VEGF); this condition is also associated with acute activation of the hypothalamo-pituitary-adrenal (HPA) axis, suggesting that increased levels of EPO and VEGF in the hypothalamus may play a role in the control of HPA function. Thus, in this study we used rat hypothalamic explants to investigate whether EPO and VEGF can directly modulate CRH release; the latter was assessed by RIA measurement of the peptide in the incubation medium and hypothalamic tissue. EPO and VEGF effects were studied in short-term (1–3 h) experiments under basal conditions or after stimulation with 56 mM KCl or 10 μM veratridine. We observed that EPO (1–10 nm) significantly reduced CRH release and, in parallel, increased intrahypothalamic CRH content. VEGF tended to reduce CRH release without reaching statistical significance. Moreover, EPO, but not VEGF, inhibited KCl- and veratridine-stimulated CRH release and counteracted the parallel decrease in intrahypothalamic CRH induced by the two secretagogues. EPO effects were not mediated by modification of CRH gene expression, either in the absence or the presence of KCl or veratridine; in this paradigm, KCl and veratridine per se did not modify CRH gene expression. Our findings suggest that EPO contributes to the regulation of the HPA axis activation; in pathological conditions such as brain ischemia, this growth factor may control the HPA axis function, preventing possible detrimental effects of HPA overactivation

Aloe arborescens Extract Protects IMR-32 Cells against Alzheimer Amyloid Beta Peptide via Inhibition of Radical Peroxide Production.

Aloe arborescens is commonly used as a pharmaceutical ingredient for its effect in burn treatment and ability to increase skin wound healing properties. Besides, it is well known to have beneficial phytotherapeutic, anticancer, and radio-protective properties. In this study, we first provided evidence that A. arborescens extract protects IMR32, a neuroblastoma human cellular line, from toxicity induced by beta amyloid, the peptide responsible for Alzheimer's disease. In particular, pretreatment with A. arborescens maintains an elevated cell viability and exerts a protective effect on mitochondrial functionality, as evidenced by oxygen consumption experiments. The protective mechanism exerted by A. arborescens seems be related to lowering of oxidative potential of the cells, as demonstrated by the ROS measurement compared with the results obtained in the presence of amyloid beta (1–42) peptide alone. Based on these preliminary observations we suggest that use of A. arborescens extract could be developed as agents for the management of AD

CHILDHOOD DEPRESSION: A DESCRIPTIVE STUDY ON A GROUP OF CHILDREN/STUDENTS IN PALERMO

An investigation was carried out on a group of students, 7-10 years old, aimed to evidence the presence of same of common symptoms of depression in childhood. Results reported demonstrated that more than 50% of the sample was often sad, nervous, anxious and suffers of sleeping disorders. The need was stressed of on early and correct diagnosis of infantile depression to sustain the child’s development and to give adequate treatment

Cytoprotective Effect of Idebenone through Modulation of the Intrinsic Mitochondrial Pathway of Apoptosis in Human Retinal Pigment Epithelial Cells Exposed to Oxidative Stress Induced by Hydrogen Peroxide

Idebenone is a ubiquinone short-chain synthetic analog with antioxidant properties, which is believed to restore mitochondrial ATP synthesis. As such, idebenone is investigated in numerous clinical trials for diseases of mitochondrial aetiology and it is authorized as a drug for the treatment of Leber’s hereditary optic neuropathy. Mitochondria of retinal pigment epithelium (RPE) are particularly vulnerable to oxidative damage associated with cellular senescence. Therefore, the aim of this study was to explore idebenone’s cytoprotective effect and its underlying mechanism. We used a human-RPE cell line (ARPE-19) exposed to idebenone pre-treatment for 24 h followed by conditions inducing H2O2 oxidative damage for a further 24 h. We found that idebenone: (a) ameliorated H2O2-lowered cell viability in the RPE culture; (b) activated Nrf2 signaling pathway by promoting Nrf2 nuclear translocation; (c) increased Bcl-2 protein levels, leaving unmodified those of Bax, thereby reducing the Bax/Bcl-2 ratio; (d) maintained the mitochondrial membrane potential (ΔΨm) at physiological levels, preserving the functionality of mitochondrial respiratory complexes and counteracting the excessive production of ROS; and (e) reduced mitochondrial cytochrome C-mediated caspase-3 activity. Taken together, our findings show that idebenone protects RPE from oxidative damage by modulating the intrinsic mitochondrial pathway of apoptosis, suggesting its possible role in retinal epitheliopathies associated with mitochondrial dysfunction

Cannabidiol tempers alcohol intake and neuroendocrine and behavioural correlates in alcohol binge drinking adolescent rats. Focus on calcitonin gene-related peptide's brain levels

: Alcohol binge drinking is common among adolescents and may challenge the signalling systems that process affective stimuli, including calcitonin gene-related peptide (CGRP) signalling. Here, we employed a rat model of adolescent binge drinking to evaluate reward-, social- and aversion-related behaviour, glucocorticoid output and CGRP levels in affect-related brain regions. As a potential rescue, the effect of the phytocannabinoid cannabidiol was explored. Adolescent male rats underwent the intermittent 20% alcohol two-bottle choice paradigm; at the binge day (BD) and the 24 h withdrawal day (WD), we assessed CGRP expression in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), amygdala, hypothalamus and brainstem; in addition, we evaluated sucrose preference, social motivation and drive, nociceptive response, and serum corticosterone levels. Cannabidiol (40 mg/kg, i.p.) was administered before each drinking session, and its effect was measured on the above-mentioned readouts. At BD and WD, rats displayed decreased CGRP expression in mPFC, NAc and amygdala; increased CGRP levels in the brainstem; increased response to rewarding- and nociceptive stimuli and decreased social drive; reduced serum corticosterone levels. Cannabidiol reduced alcohol consumption and preference; normalised the abnormal corticolimbic CGRP expression, and the reward and aversion-related hyper-responsivity, as well as glucocorticoid levels in alcohol binge-like drinking rats. Overall, CGRP can represent both a mediator and a target of alcohol binge-like drinking and provides a further piece in the intricate puzzle of alcohol-induced behavioural and neuroendocrine sequelae. CBD shows promising effects in limiting adolescent alcohol binge drinking and rebalancing the bio-behavioural abnormalities

CBD enhances the cognitive score of adolescent rats prenatally exposed to THC and fine-tunes relevant effectors of hippocampal plasticity

Introduction: An altered neurodevelopmental trajectory associated with prenatal exposure to ∆-9-tetrahydrocannabinol (THC) leads to aberrant cognitive processing through a perturbation in the effectors of hippocampal plasticity in the juvenile offspring. As adolescence presents a unique window of opportunity for “brain reprogramming”, we aimed at assessing the role of the non-psychoactive phytocannabinoid cannabidiol (CBD) as a rescue strategy to temper prenatal THC-induced harm.Methods: To this aim, Wistar rats prenatally exposed to THC (2 mg/kg s.c.) or vehicle (gestational days 5–20) were tested for specific indexes of spatial and configural memory in the reinforcement-motivated Can test and in the aversion-driven Barnes maze test during adolescence. Markers of hippocampal excitatory plasticity and endocannabinoid signaling—NMDAR subunits NR1 and 2A-, mGluR5-, and their respective scaffold proteins PSD95- and Homer 1-; CB1R- and the neuromodulatory protein HINT1 mRNA levels were evaluated. CBD (40 mg/kg i.p.) was administered to the adolescent offspring before the cognitive tasks.Results: The present results show that prenatal THC impairs hippocampal memory functions and the underlying synaptic plasticity; CBD is able to mitigate cognitive impairment in both reinforcement- and aversion-related tasks and the neuroadaptation of hippocampal excitatory synapses and CB1R-related signaling.Discussion: While this research shows CBD potential in dampening prenatal THC-induced consequences, we point out the urgency to curb cannabis use during pregnancy in order to avoid detrimental bio-behavioral outcomes in the offspring

Proinflammatory-activated trigeminal satellite cells promote neuronal sensitization: relevance for migraine pathology.

BACKGROUND: Migraine is a complex, chronic, painful, neurovascular disorder characterized by episodic activation of the trigeminal system. Increased levels of calcitonin gene-related peptide (CGRP) are found at different levels during migraine attacks. Interestingly, CGRP is also released within the trigeminal ganglia suggesting possible local effects on satellite cells, a specialized type of glia that ensheaths trigeminal neurons. CGRP was shown to enhance satellite-cell production of interleukin 1beta (IL-1beta), while trigeminal neurons express an activity-dependent production of nitric oxide (NO). Thus, in the present study we tested the hypothesis that IL-1beta and NO induce trigeminal satellite cell activation, and that once activated these cells can influence neuronal responses. RESULTS: Primary cultures of rat trigeminal satellite cells isolated from neuronal cultures were characterized in vitro. Cyclooxygenase (COX) expression and activity were taken as a marker of glial pro-inflammatory activation. Most of the experiments were carried out to characterize satellite cell responses to the two different pro-inflammatory stimuli. Subsequently, medium harvested from activated satellite cells was used to test possible modulatory effects of glial factors on trigeminal neuronal activity. IL-1beta and the NO donor diethylenetriamine/nitric oxide (DETA/NO) elevated PGE2 release by satellite cells. The stimulatory effect of IL-1beta was mediated mainly by upregulation of the inducible form of COX enzyme (COX2), while NO increased the constitutive COX activity. Regardless of the activator used, it is relevant that short exposures of trigeminal satellite cells to both activators induced modifications within the cells which led to significant PGE2 production after removal of the pro-inflammatory stimuli. This effect allowed us to harvest medium from activated satellite cells (so-called 'conditioned medium') that did not contain any stimulus, and thus test the effects of glial factors on neuronal activation. Conditioned medium from satellite cells activated by either IL-1beta or NO augmented the evoked release of CGRP by trigeminal neurons. CONCLUSION: These findings indicate that satellite cells contribute to migraine-related neurochemical events and are induced to do so by autocrine/paracrine stimuli (such as IL-1beta and NO). The responsiveness of IL-1beta to CGRP creates the potential for a positive feedback loop and, thus, a plurality of targets for therapeutic intervention in migraine

Punicalagin reduces H(2)O(2)-induced cytotoxicity and apoptosis in PC12 cells by modulating the levels of reactive oxygen species

BACKGROUND: Oxidative stress has long been linked to neuronal cell death in many neurodegenerative diseases. Antioxidant conventional supplements are poorly effective in preventing neuronal damage caused by oxidative stress due to their inability to cross the blood brain barrier. Hence the use of molecules extracted from plants and fruits such as phenolics, flavonoids, and terpenoids compounds constitute a new wave of antioxidant therapies to defend against free radicals. OBJECTIVE: In this study we examined the effects of punicalagin, a ellagitannin isolated from the pomegranate juice, on a rat adrenal pheochromocytoma cell line, treated with hydrogen peroxide, evaluating the viability, oxidation potential, mitochondrial function, and eventual apoptosis. METHODS: This study was performed on PC12 cells pretreated with punicalagin (0.5, 1, 5, 10 e 20 µM) 24 hours before of the damage by hydrogen peroxide (H2O2). H2O2 concentration (300 µM) used in our study was determined by preliminary experiments of time course. The cell viability and ROS production were evaluated by MTS assay and cytofluorometry assays, respectively. Subsequently, the number of apoptotic-positive cells and mitochondrial transmembrane potential, were measured by flow cytometry, in the same experimental paradigm. Finally, the expression of Bax and enzymatic activity of Caspase 3, some of the principle actors of programmed cell death, were investigated by semiquantitative PCR and utilizing a colorimetric assay kit, respectively. RESULTS: We found that pretreatment with punicalagin protected the cells from H2O2-induced damage. In particular, the protective effect seemed to be correlated with a control both in radical oxygen species production and in mitochondrial functions. In fact the cells treated with H2O2 showed an altered mitochondrial membrane integrity while the pretreatment with punicalagin retained both the cellular viability and the mitochondrial membrane potential similar to the control. Furthermore, the punicalagin, modulated the apoptotic cascade triggered reducing Bax gene expression and Caspase 3 activity. DISCUSSION: Results of the present study demonstrated a neuroprotective effect of punicalagin on H2O2-induced PC12 cell death, including mitochondria damage and expression of apoptotic gene Bax; therefore we hypothesize a possible prevent role for this molecule in neurodegenerative diseases related to oxidative stress

Il cibo come farmaco: probiotici, prebiotici, simbiotici

Enteric microflora represent a protective barrier against infectious viruses, bacteria and toxins. Nutritional supplements constituted of live germs, producing and maintaining a condition of enteric eubioses may offer therapeutic possibilities against different pathologies