Circadian Behaviour in Neuroglobin Deficient Mice

Neuroglobin (Ngb), a neuron-specific oxygen-binding globin with an unknown function, has been proposed to play a key role in neuronal survival. We have previously shown Ngb to be highly expressed in the rat suprachiasmatic nucleus (SCN). The present study addresses the effect of Ngb deficiency on circadian behavior. Ngb-deficient and wild-type (wt) mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1) and the immediate early gene Fos was determined after light stimulation at night and the neurochemical phenotype of Ngb expressing neurons in wt mice was characterized. Loss of Ngb function had no effect on overall circadian entrainment, but resulted in a significantly larger phase delay of circadian rhythm upon light stimulation at early night. A light-induced increase in Per1, but not Fos, gene expression was observed in Ngb-deficient mice. Ngb expressing neurons which co-stored Gastrin Releasing Peptide (GRP) and were innervated from the eye and the geniculo-hypothalamic tract expressed FOS after light stimulation. No PER1 expression was observed in Ngb-positive neurons. The present study demonstrates for the first time that the genetic elimination of Ngb does not affect core clock function but evokes an increased behavioural response to light concomitant with increased Per1 gene expression in the SCN at early night

Circadian Integration of Glutamatergic Signals by Little SAAS in Novel Suprachiasmatic Circuits

Neuropeptides are critical integrative elements within the central circadian clock in the suprachiasmatic nucleus (SCN), where they mediate both cell-to-cell synchronization and phase adjustments that cause light entrainment. Forward peptidomics identified little SAAS, derived from the proSAAS prohormone, among novel SCN peptides, but its role in the SCN is poorly understood.Little SAAS localization and co-expression with established SCN neuropeptides were evaluated by immunohistochemistry using highly specific antisera and stereological analysis. Functional context was assessed relative to c-FOS induction in light-stimulated animals and on neuronal circadian rhythms in glutamate-stimulated brain slices. We found that little SAAS-expressing neurons comprise the third most abundant neuropeptidergic class (16.4%) with unusual functional circuit contexts. Little SAAS is localized within the densely retinorecipient central SCN of both rat and mouse, but not the retinohypothalamic tract (RHT). Some little SAAS colocalizes with vasoactive intestinal polypeptide (VIP) or gastrin-releasing peptide (GRP), known mediators of light signals, but not arginine vasopressin (AVP). Nearly 50% of little SAAS neurons express c-FOS in response to light exposure in early night. Blockade of signals that relay light information, via NMDA receptors or VIP- and GRP-cognate receptors, has no effect on phase delays of circadian rhythms induced by little SAAS.Little SAAS relays signals downstream of light/glutamatergic signaling from eye to SCN, and independent of VIP and GRP action. These findings suggest that little SAAS forms a third SCN neuropeptidergic system, processing light information and activating phase-shifts within novel circuits of the central circadian clock

Lesion locations influencing baseline severity and early recovery in ischaemic stroke

Item does not contain fulltextBackground and purpose: Strokes caused by lesions to certain brain areas are associated with poor outcome, which is important both prognostically and to understand the neural basis for recovery. However, lesion anatomy associations with outcome may occur because of effects on baseline severity rather than because of effects on recovery per se. Here, all common stroke locations were surveyed to determine the strongest lesion anatomy associations separately for baseline functional severity and proportional recovery. Since most recovery occurs early, the focus here is on functional changes over the first week. Method: Global functional scores (National Institutes of Health Stroke Scale) at baseline and proportional recovery over 1 week were derived from the records of 550 ischaemic stroke patients and related to magnetic resonance imaging lesion location using voxel-lesion mapping. The effects of lesions extending over more than one location were also considered. Cross-validation estimated the percentage of recovery rate variance (r(2)) accountable by lesion location information. Results: High baseline severity was associated with lesions to the left capsule, striatum and thalamocortical white matter, whereas high recovery rate was associated with lesions to more superficial left fronto-temporal areas. Low recovery rates were associated with lesions to bilateral parietal, right insula, medial frontal, capsule and brainstem. Inclusion of these regions into a multivariate model of proportional recovery rate increased r(2) from 8% to 45%. Conclusion: The strongest stroke lesion location associations with 1-week recovery were identified, and it was shown that anatomical information accounts for a sizeable proportion of early recovery variability