Pannexin 1 regulates postnatal neural stem and progenitor cell proliferation

<p>Abstract</p> <p>Background</p> <p>Pannexin 1 forms ion and metabolite permeable hexameric channels and is abundantly expressed in the brain. After discovering pannexin 1 expression in postnatal neural stem and progenitor cells we sought to elucidate its functional role in neuronal development.</p> <p>Results</p> <p>We detected pannexin 1 in neural stem and progenitor cells <it>in vitro</it> and <it>in vivo</it>. We manipulated pannexin 1 expression and activity in Neuro2a neuroblastoma cells and primary postnatal neurosphere cultures to demonstrate that pannexin 1 regulates neural stem and progenitor cell proliferation likely through the release of adenosine triphosphate (ATP).</p> <p>Conclusions</p> <p>Permeable to ATP, a potent autocrine/paracine signaling metabolite, pannexin 1 channels are ideally suited to influence the behavior of neural stem and progenitor cells. Here we demonstrate they play a robust role in the regulation of neural stem and progenitor cell proliferation. Endogenous postnatal neural stem and progenitor cells are crucial for normal brain health, and their numbers decline with age. Furthermore, these special cells are highly responsive to neurological injury and disease, and are gaining attention as putative targets for brain repair. Therefore, understanding the fundamental role of pannexin 1 channels in neural stem and progenitor cells is of critical importance for brain health and disease.</p

Repetitive Transcranial Magnetic Stimulation in Youth With Treatment Resistant Major Depression

Background: Major depressive disorder (MDD) is common in youth and treatment options are limited. We evaluated the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) in adolescents and transitional aged youth with treatment resistant MDD.Methods: Thirty-two outpatients with moderate to severe, treatment-resistant MDD, aged 13–21 years underwent a three-week, open-label, single center trial of rTMS (ClinicalTrials.gov identifier NCT01731678). rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) using neuronavigation and administered for 15 consecutive week days (120% rest motor threshold; 40 pulses over 4 s [10 Hz]; inter-train interval, 26 s; 75 trains; 3,000 pulses). The primary outcome measure was change in the Hamilton Depression Rating Scale (Ham-D). Treatment response was defined as a &gt;50% reduction in Ham-D scores. Safety and tolerability were also examined.Results: rTMS was effective in reducing MDD symptom severity (t = 8.94, df = 31, p &lt; 0.00001). We observed 18 (56%) responders (≥ 50% reduction in Ham-D score) and 14 non-responders to rTMS. Fourteen subjects (44%) achieved remission (Ham-D score ≤ 7 post-rTMS). There were no serious adverse events (i.e., seizures). Mild to moderate, self-limiting headaches (19%) and mild neck pain (16%) were reported. Participants ranked rTMS as highly tolerable. The retention rate was 91% and compliance rate (completing all study events) was 99%.Conclusions: Our single center, open trial suggests that rTMS is a safe and effective treatment for youth with treatment resistant MDD. Larger randomized controlled trials are needed.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT0173167

Photoswitching Using Visible Light: A New Class of Organic Photochromic Molecules

A versatile new class of organic photochromic molecules that offers an unprecedented combination of physical properties including tunable photoswitching using visible light, excellent fatigue resistance, and large polarity changes is described. These unique features offer significant opportunities in diverse fields ranging from biosensors to targeted delivery systems while also allowing non-experts ready synthetic access to these materials

The influence of the freshwater environment and the biological characteristics of Atlantic salmon smolts on their subsequent marine survival

Atlantic salmon have declined markedly in the past 20-30 years throughout their range. Much of the focus for this decline has been on increased mortality during the marine phase of the life cycle. However, marine mortality does not operate independently of factors acting in freshwater and the biological characteristics of smolts migrating to sea. Over recent decades, juvenile salmon in many rivers have grown faster and migrated to sea at a younger age, and thus typically smaller. This has shortened the generation time for many individuals, and may dampen the impact of increased marine mortality, assuming expected higher in-river survival prior to smolting is not outweighed by increased mortality of smaller smolts at sea. Over the same period, smolt run-timing across the geographic range has been occurring earlier, at a rate of almost three days per decade, on average. This has given rise to growing concerns about smolts potentially missing the optimum environmental migration “window”, the timing of which may also be changing. Contaminants and other factors operating in freshwater also impact on smolt quality with adverse consequences for their physiological readiness for life at sea. Given that managers have very limited ability to influence the broad scale factors limiting salmon survival at sea, it is vital that freshwater habitats are managed to both maximise smolt output and to minimise the impact of factors acting in freshwater which may compromise salmon once they migrate to sea.Publisher PDFPeer reviewe

Craving and emotional responses to trauma and cannabis cues in trauma-exposed cannabis users: influence of PTSD symptom severity

Conditioned craving to trauma cues and avoidance learning have both been implicated in the high concurrence of trauma-related distress and substance misuse. Using a cue-exposure paradigm involving personalized trauma, cannabis, and neutral cues, we examined if conditioned craving and/or elevated negative affect to trauma cues are mechanisms linking PTSD and cannabis use disorder. Fifty-one trauma-exposed cannabis users were randomly presented the three cue types. Craving and emotional responses were evaluated after each cue using the Marijuana Craving Questionnaire–Short Form (Heishman et al., 2001) and the Positive and Negative Affect Schedule (Watson et al., 1988). Relief cannabis craving (compulsivity and emotionality) was significantly higher after trauma than cannabis and neutral cues (p's < 0.001) and was also higher among those with more severe PTSD symptoms (p's < 0.05). The relationship between PTSD symptom severity and cannabis craving was stronger after trauma than cannabis cues for the compulsivity component of craving (p < .05). Relief craving was also higher after the cannabis cue than after the neutral cue (expectancy and purposefulness; p < .001). Negative affect was significantly higher: after trauma than cannabis and neutral cues (p's < 0.001); and among those with more severe PTSD symptoms (p <. 005). Positive affect was significantly lower after trauma than cannabis cues (p < .05). Trauma cue exposure might promote cannabis misuse through conditioned craving as well as the desire to relieve negative affect. Conditioned cannabis craving involving an uncontrollable compulsion to use cannabis in response to trauma reminders appears particularly likely among cannabis users with more severe PTSD symptoms

Safety and tolerability of transcranial magnetic and direct current stimulation in children: prospective single center evidence from 3.5 million stimulations

Background: Non-invasive brain stimulation is being increasingly used to interrogate neurophysiology and modulate brain function. Despite the high scientific and therapeutic potential of non-invasive brain stimulation, experience in the developing brain has been limited. Objective: To determine the safety and tolerability of non-invasive neurostimulation in children across diverse modalities of stimulation and pediatric populations. Methods: A non-invasive brain stimulation program was established in 2008 at our pediatric, academic institution. Multi-disciplinary neurophysiological studies included single- and paired-pulse Transcranial Magnetic Stimulation (TMS) methods. Motor mapping employed robotic TMS. Interventional trials included repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS). Standardized safety and tolerability measures were completed prospectively by all participants. Results: Over 10 years, 384 children underwent brain stimulation (median 13 years, range 0.8–18.0). Populations included typical development (n = .118), perinatal stroke/cerebral palsy (n = .101), mild traumatic brain injury (n = .121) neuropsychiatric disorders (n = .37), and other (n = .7). No serious adverse events occurred. Drop-outs were rare (100 participants having brain injuries and/or epilepsy. Tolerability between single and paired-pulse TMS (542340 stimulations) and rTMS (3.0 million stimulations) was comparable and favourable. TMS-related headache was more common in perinatal stroke (40%) than healthy participants (13%) but was mild and self-limiting. Tolerability improved over time with side-effect frequency decreasing by >50%. Robotic TMS motor mapping was well-tolerated though neck pain was more common than with manual TMS (33% vs 3%). Across 612 tDCS sessions including 92 children, tolerability was favourable with mild itching/tingling reported in 37%. Conclusions: Standard non-invasive brain stimulation paradigms are safe and well-tolerated in children and should be considered minimal risk. Advancement of applications in the developing brain are warranted. A new and improved pediatric NIBS safety and tolerability form is included