The primate-specific peptide Y-P30 regulates morphological maturation of neocortical dendritic spines

The 30-amino acid peptide Y-P30 corresponds to the N-terminus of the primate-specific, sweat gland-derived dermcidin prepropeptide. Previous work has revealed that Y-P30 enhances the interaction of pleiotrophin and syndecans-2/3, and thus represents a natural ligand to study this signaling pathway. In immature neurons, Y-P30 activates the c-Src and p42/44 ERK kinase pathway, increases the amount of F-actin in axonal growth cones, and promotes neuronal survival, cell migration and axonal elongation. The action of Y-P30 on axonal growth requires syndecan-3 and heparan sulfate side chains. Whether Y-P30 has the potential to influence dendrites and dendritic protrusions has not been explored. The latter is suggested by the observations that syndecan-2 expression increases during postnatal development, that syndecan-2 becomes enriched in dendritic spines, and that overexpression of syndecan-2 in immature neurons results in a premature morphological maturation of dendritic spines. Here, analysing rat cortical pyramidal and non-pyramidal neurons in organotypic cultures, we show that Y-P30 does not alter the development of the dendritic arborization patterns. However, Y-P30 treatment decreases the density of apical, but not basal dendritic protrusions at the expense of the filopodia. Analysis of spine morphology revealed an unchanged mushroom/stubby-to-thin spine ratio and a shortening of the longest decile of dendritic protrusions. Whole-cell recordings from cortical principal neurons in dissociated cultures grown in the presence of Y-P30 demonstrated a decrease in the frequency of glutamatergic mEPSCs. Despite these differences in protrusion morphology and synaptic transmission, the latter likely attributable to presynaptic effects, calcium event rate and amplitude recorded in pyramidal neurons in organotypic cultures were not altered by Y-P30 treatment. Together, our data suggest that Y-P30 has the capacity to decelerate spinogenesis and to promote morphological, but not synaptic, maturation of dendritic protrusions.Peer reviewe

PET Imaging in Altered States of Consciousness: Coma, Sleep, and Hypnosis

peer reviewedPositron emission tomography (PET) allows studies of cerebral metabolism and blood flow and has been widely used to investigate physiological mechanisms underlying altered states of consciousness. Consciousness is characterized by two components: wakefulness and awareness. In this chapter, we review the current literature on brain metabolism during pathological loss of consciousness (vegetative/unresponsive or minimally conscious states), sleep (in healthy subjects and in patients with insomnia), and under hypnosis. By identifying brain areas specifically involved in conscious processing, these studies have contributed to our understanding of the underlying physiology of consciousness. The precuneal and cingulate cortices, for example, seem to be key areas for maintaining conscious awareness. FDG-PET further allowed the identification of the minimal energetic requirement for conscious awareness in this population, which corresponds to 42% of normal cortical activity. Up to now, it is the most accurate neuroimaging tool regarding the diagnosis of patients with disorders of consciousness. In the future, its use as part of multimodal assessment could improve diagnosis and prognosis in this challenging population. In sleep, a greater activity of the precuneus/posterior cingulate cortex and the fronto-parietal areas during non rapid eye movement sleep also seems to play a role in disorders such as insomnia. Other areas such as the hypothalamus, amygdala, or temporo-occipital cortex seem to play a role in different states such as rapid eye movement sleep and hypnosis. PET studies permit a better comprehension of the neural correlates of consciousness and to identify the implication of specific neural areas and networks in altered states of consciousness in post-comatose patients, sleep and induced hypnosis