SUMMARY BackgroundThe intestinal permeability is increased in patients with diarrhoeapredominant irritable bowel syndrome (D-IBS).

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Substantial development in the pharmacological treatment for attention-deficit hyperactivity disorder (ADHD) has been made recently including approval of new non-stimulant agents targeting noradrenergic, histaminergic and dopaminergic systems. Among such, atomoxetine has been widely used, although its mechanism of action is poorly understood. It is known that central nervous system histamine is closely associated with cognition and it was recently shown that both atomoxetine and methylphenidate enhance cortical histamine release in rats. To that end, the aim of our study was to investigate the effect of atomoxetine (2 mg/kg, intraperitoneally) on histamine release using the microdialysis technique in the spontaneously hypertensive rat (SHR), a suitable genetic model for ADHD. Our data confirmed that atomoxetine increases extracellular levels of histamine in the prefrontal cortex, a brain region that is implicated in the pathophysiology of ADHD. Given the tie between histamine neurotransmission and treatment of cognitive dysfunction, we also assessed the effects of atomoxetine on learning and memory as measured by the Morris water maze in SHR. The results indicated that atomoxetine significantly ameliorated performance in the Morris water maze, consistent with its histamine-enhancing profile. In conclusion, the current study provides further support for the notion that the therapeutic effect of atomoxetine could involve activation of histamine neurotransmission within the prefrontal cortex.Attention-deficit hyperactivity disorder (ADHD) is one of the most commonly seen chronic health conditions featured by mental disorders in school-aged children and is characterized by elevated, age-inappropriate levels of inattention, impulsivity and excessive motor activity [1,2]. In addition, ADHD children usually experience problems with cognitive impulsiveness that are sometimes defined as planning deficits, forgetfulness and poor management of time [3].Spontaneously hypertensive rats (SHR) are considered as an animal model of ADHD because they display hyperactivity, impulsivity, poorly sustained attention and deficits in the learning and memory processes [4][5][6]. Furthermore, substandard performance has been noted in SHRs in a number of paradigms commonly used to evaluate learning and memory, such as the Morris water maze [7,8], the radial-arm maze [9] and the two-way shuttle box avoidance task [10]. For this reason, SHRs have been recommended as a unique model to evaluate pharmacological agents with therapeutic potential for disorders of memory and attention [8].To date, the 'dopaminergic hypothesis' based on a dysregulation in dopaminergic neurotransmission, has been the most widely accepted theory for behavioural alterations in both ADHD patients and SHR rats. There is considerable evidence suggesting that ADHD patients have disturbances in dopamine uptake, storage and/or metabolism [11][12][13][14][15]. Furthermore, SHR, a suitable model for ADHD, displays reduced release of dopamine in the prefrontal corte...

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Granulocyte colony-stimulating factor (G-CSF) and its related mechanisms were investigated to assess the potential for this factor to exert neuroprotective effects against spinal cord injury in mice. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was injected into mice spinal cord hemisection models. Locomotor activity was assessed by using the Basso-Bettie-Bresnahan scale. Neurons isolated from spinal cords were cultured in vitro and used in a neuronal mechanical injury model. Three treatment groups were compared with this model, 1) G-CSF, 2) G-CSF + NSC348884 (a nucleophosmin 1-specific inhibitor), and 3) NSC348884. Immunofluorescence staining and Western blotting were performed to analyze the expression of G-CSF and nucleophosmin 1 (Npm1). TUNEL staining was performed to analyze apoptosis after G-CSF treatment. We found that the G-CSF receptor (G-CSFR) and Npm1 were expressed in neurons and that Npm1 expression was induced after G-CSF treatment. G-CSF inhibited neuronal apoptosis. NSC348884 induced p53-dependent cell apoptosis and partially blocked the neuroprotective activity of G-CSF on neurons in vitro. G-CSF promoted locomotor recovery and demonstrated neuroprotective effects in an acute spinal cord injury model. The mechanism of G-CSF's neuroprotection may be related in part to attenuating neuronal apoptosis by NPM1.