Role of polysialylated neural cell adhesion molecule in rapid eye movement sleep regulation in rats

Abstract

Recent evidence suggests that synaptic plasticity occurs during homeostatic processes, including sleep-wakefulness regulation, although the underlying mechanisms are not well understood. Polysialylated neural cell adhesion molecule (PSA NCAM) is a transmembrane protein that has been implicated in various forms of plasticity. To investigate whether PSA NCAM is involved in the neuronal plasticity associated with spontaneous sleep-wakefulness regulation and sleep homeostasis, four studies were conducted using rats. First, we showed that PSA NCAM immunoreactivity is present in close proximity to key neurons in several nuclei of the sleep-wakefulness system, including the tuberomammillary hypothalamic nucleus, dorsal raphe nucleus, and locus coeruleus. Second, using western blot analysis and densitometric image analysis of immunoreactivity, we found that 6 h of sleep deprivation changed neither the levels nor the general location of PSA NCAM in the sleep-wakefulness system. Finally, we injected endoneuraminidase (Endo N) intracerebroventricularly to examine the effects of polysialic acid removal on sleep-wakefulness states and electroencephalogram (EEG) slow waves at both baseline and during recovery from 6 h of sleep deprivation. Endo N-treated rats showed a small but significant decrease in baseline rapid eye movement (REM) sleep selectively in the late light phase, and a facilitated REM sleep rebound after sleep deprivation, as compared with saline-injected controls. Non-REM sleep and wakefulness were unaffected by Endo N. These results suggest that PSA NCAM is not particularly involved in the regulation of wakefulness or non-REM sleep, but plays a role in the diurnal pattern of REM sleep as well as in some aspects of REM sleep homeostasis.

Brain Control of Plasma Cholesterol Involves Polysialic Acid Molecules in the Hypothalamus

“…Given the role of PSA in the control of synaptic plasticity (Rutishauser, 2008), these findings suggest that blood cholesterol homeostasis might be regulated via neuronal rewiring within hypothalamic circuits. Above all, this shows that hypothalamic PSA coordinates many aspects of metabolism and energy balance including peripheral lipid metabolism as well as food intake (Benani et al, 2012), osmoregulation (Theodosis et al, 1999), circadian rhythm (Shen et al, 1997; Glass et al, 2000; Fedorkova et al, 2002; Prosser et al, 2003), and sleep (Black et al, 2009). However, mechanisms by which hypothalamic PSA affects plasma levels of LDL and HDL cholesterol remains to be elucidated.…”

“…The attachment of PSA to cell-surface proteins reduces cell interactions and promotes synaptic changes and other plasticity-related events in the brain (Rutishauser, 2008). In the hypothalamus, PSA is involved in many aspects of energy balance including food intake (Benani et al, 2012), osmoregulation (Theodosis et al, 1999), circadian rhythm (Shen et al, 1997; Glass et al, 2000; Fedorkova et al, 2002; Prosser et al, 2003), and sleep (Black et al, 2009). In this work, we investigated whether PSA also contributes to the homeostatic control of plasma cholesterol.…”

Depletion of polysialic acid from neural cell adhesion molecule (PSA-NCAM) increases CA3 dendritic arborization and increases vulnerability to excitotoxicity

“…The dose is based on published doses for both intraparenchymal and ICV administration e.g. (Black, et al, 2009). …”

Glial cell line‐derived neurotrophic factor‐mediated enhancement of noradrenergic descending inhibition in the locus coeruleus exerts prolonged analgesia in neuropathic pain

“…Because GDNF injections that missed the LC had no analgesic effect, the LC is most likely site responsible for the effects of GDNF. Consistent with our results, the GDNF receptor components GFRα‐1, Ret and NCAM are all expressed by noradrenergic neurons in the LC (Trupp et al ., ; Glazner et al ., ; Golden et al ., ; Sarabi et al ., ; Black et al ., ). The GDNF‐induced analgesia was blocked by the spinal administration of the α 2 ‐adrenoceptor antagonist yohimbine in the present study.…”

“…In situ hybridization revealed that GFRα‐1 and Ret are expressed by LC noradrenergic neurons (Trupp et al ., ; Glazner et al ., ; Golden et al ., ; Sarabi et al ., ). NCAM expression is also observed in noradrenergic neurons in the LC (Black et al ., ). Consistent with its neurotrophic effect, extensive catecholaminergic neuronal death in the LC is observed in the conditional GDNF‐deficient mouse (Pascual et al ., ).…”