Roles of neuregulin in synaptogenesis between mossy fibers and cerebellar granule cells

Ozaki, Miwako; Tohyama, Koujiro; Kishida, Haruo; Buonanno, Andrés; Yano, Ryoji; Hashikawa, Tsutomu

doi:10.1002/(sici)1097-4547(20000301)59:5<612::aid-jnr4>3.0.co;2-v

Cited by 48 publications

(28 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ozaki and colleagues analyzed the expression of ErbB2, ErbB3 and ErbB4 proteins and mRNA in the developing mouse cerebellum, showing strong expression of the receptors in the postnatal period with a peak at P18 followed by a strong decrease in the adult age (Ozaki et al, 1998). This matches the peak of major synaptic organization of the cerebellum and is consistent with roles for neuregulin in synaptogenesis (Ozaki et al, 2000). In the olfactory bulb, ErbB3 and ErbB4-JMb reach maximal expression around P4-P8 and decrease toward the adult age.…”

Section: Discussionmentioning

confidence: 70%

Differential expression of neuregulins and their receptors in the olfactory bulb layers of the developing mouse

et al. 2006

View full text Add to dashboard Cite

Neuregulins (NRGs), and their cognate receptors (ErbBs), play essential roles in numerous aspects of neural development and adult synaptic plasticity. The goal of this study was to investigate the developmental expression profiles of these molecules during the olfactory bulb (OB) maturation. The OB is a highly organized structure with cell types and synaptic connections segregated into discrete anatomical layers. We employed a novel approach by combining single-layer microdissection at different development ages,with isoform-specific semi-quantitative RT-PCR and Western blotting to monitor layer-specific developmental profiles of these molecules and alternate splice variants. Layer and age specific regulation was observed for the ErbB4 splice variants JMa/JMb and NRG-1-β1/β2 forms. With the exception of the outermost (nerve) layer, ErbB4-JMb and NRG-1-β1 are expressed throughout the OB and their expressions decrease in the adult age in most layers. In contrast both ErbB4-JMa and NRG-1-β2 are highly expressed in the granule cell layer in the early postnatal OB. This early postnatal expression correlates with the dramatic change from radial glia to astrocytes and appearance of the bulk of granule cells occurring at this developmental stage.

show abstract

Section: Discussionmentioning

confidence: 70%

Differential expression of neuregulins and their receptors in the olfactory bulb layers of the developing mouse

et al. 2006

View full text Add to dashboard Cite

show abstract

“…NRG1 secreted from either neurons or glial cells bind to the extracellular domains of the receptor tyrosine kinases ErbB3 and ErbB4 to initiate a signaling cascade that results in a wide range of biological effects that include modulation of synaptic activity and synaptogenesis (Ozaki et al, 1997;Ozaki et al, 2000;Wolpowitz et al, 2000), induction of neurite arborization (Gerecke et al, 2004), and regulation of the survival and maturation of glial cells (Lemke and Brockes, 1984;Syroid et al, 1996;Adlkofer and Lai, 2000;Chen et al, 2003). Our previous findings indicate that NRG1 is regulated by gonadal steroids, particularly progesterone, in the CNS following nerve root injury.…”

Section: Introductionmentioning

confidence: 70%

Differential regulation of neuregulin 1 expression by progesterone in astrocytes and neurons

et al. 2006

View full text Add to dashboard Cite

Glial2neuronal interactions are crucial processes in neuromodulation and synaptic plasticity. The neuregulin 1 family of growth and differentiation factors have been implicated as bidirectional signaling molecules that are involved in mediating some of these interactions. We have shown previously that neuregulin 1 expression is regulated by the gonadal hormones progesterone and 17b-estradiol in the CNS, which might represent a novel, indirect mechanism of the neuromodulatory actions of these gonadal hormones. In the present study, we sought to determine the effects of progesterone and 17b-estradiol on neuregulin 1 expression in rat cortical astrocytes and neurons in vitro. We observed that progesterone increased the expression of neuregulin 1 mRNA and protein in a dose-dependent manner in cultured astrocytes, which was blocked by the progesterone receptor antagonist RU-486. In contrast, 17b-estradiol did not increase either neuregulin 1 mRNA or protein in astrocytes. We observed no effect of either progesterone or 17b-estradiol on neuregulin 1 mRNA and protein in rat cortical neurons in vitro. Finally, we observed that treatment of cortical neurons with recombinant NRG1-b1 caused PSD-95 to localize in puncta similar to that observed following treatment with astrocyte-conditioned medium. These results demonstrate that progesterone regulates neuregulin 1 expression, principally in astrocytes. This might represent a novel mechanism of progesterone-mediated modulation of neurotransmission through the regulation of astrocyte-derived neuregulin 1.Keywords: Sex hormones, neuregulin, glial activation, PSD-95, NGR1 INTRODUCTIONThe hallmark of pathological pain is sensitization of synaptic neurotransmission in the CNS. Previously, this has been attributed to aberrant neuronal activity that involved only neurons of the nociceptive axis in the CNS. However, there is increasing evidence that glial cells have a key role in modulating neuronal processes in the normal and diseased CNS. In particular, glial cells are such active participants in synaptic transmission (Parpura et al., 1994;Pfrieger and Barres, 1997;Araque et al., 2000;Ullian et al., 2001) that the functional unit of neurotransmission should now be considered to include both neuronal and glial components (De Leo et al., 2006). This is particularly true in the case of chronic pain states where glial cells are intimately involved (Garrison et al., 1994;Colburn et al., 1997;DeLeo and Yezierski, 2001;Watkins et al., 2001).The steroid hormones that are produced primarily by the gonads (i.e. 17b-estradiol, progesterone and testosterone) and their metabolites have profound neuromodulatory activities in the CNS. In the case of nociception, it has been demonstrated that manipulation of hormone levels by removing the gonads alters both basal nociceptive sensitivity and the manifestation of pain-like behaviors in several rodent models of nerve injury (Jordan, 1999;Fillingim and Ness, 2000;Craft et al., 2004). Although general observations about gonadal steroids can be made, t...

show abstract

“…In fact, NRG-1 was shown to specifically increase the expression of mRNA for the NR2C NMDA receptor subunit by more than 100-fold [27]. ErbB receptors, particularly erbB4, co-localizes with PSD-95 and NMDA receptors at postsynaptic densities and has been implicated in activity-dependent plasticity and synaptogenesis [13,28]. Overexpression of erbB4 enhanced AMPA currents and increased dendritic spine size, while reduced NRG1/erbB4 signaling resulted in glutamatergic hypofunction with a loss of NMDA currents and dendritic spines [23].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia

Ford

et al. 2007

Brain Research

View full text Add to dashboard Cite

Neuregulin-1 (NRG-1) is a growth factor with potent neuroprotective capacity in ischemic stroke. We recently showed that NRG-1 reduced neuronal death following transient middle cerebral artery occlusion (tMCAO) by up to 90% with an extended therapeutic window. Here, we examined the neuroprotective potential of NRG-1 using a permanent MCAO ischemia (pMCAO) rat model. NRG-1 reduced infarction in pMCAO by 50% when administered prior to ischemia. We previously demonstrated using gene expression profiling that pMCAO was associated with an exaggerated excitotoxicity response compared to tMCAO. Therefore, we examined whether co-treatment with an inhibitor of excitotoxicity would augment the effect of NRG-1 following pMCAO. Both NRG-1 and the N-methyl-D-aspartate (NMDA) antagonist MK-801 similarly reduced infarct size following pMCAO. However, combination treatment with both NRG-1 and MK-801 resulted in greater neuroprotection that either compound alone, including a 75% reduction in cortical infarction compared to control. Consistent with these findings, NRG-1 reduced neuronal death using an in vitro ischemia model and this effect was augmented by MK-801. These results demonstrate the efficacy of NRG-1 in pMCAO rat focal ischemia model. Our findings further indicate the potential clinically relevance of NRG-1 alone or as a combination strategy for treating ischemic stroke.

show abstract

Roles of neuregulin in synaptogenesis between mossy fibers and cerebellar granule cells

Cited by 48 publications

References 25 publications

Differential expression of neuregulins and their receptors in the olfactory bulb layers of the developing mouse

Differential expression of neuregulins and their receptors in the olfactory bulb layers of the developing mouse

Differential regulation of neuregulin 1 expression by progesterone in astrocytes and neurons

Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia

Contact Info

Product

Resources

About