Oligodendrocyte differentiation and progenitor cell proliferation are independently regulated by cyclic AMP

Raible, David W.; Fa, McMorris

doi:10.1002/jnr.490340305

Cited by 47 publications

(35 citation statements)

References 24 publications

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“…Oligodendrocytes undergo a series of sequential and well-defined changes in their phenotypic characteristics, gradually evolving from proliferative immature precursors into postmitotic mature cells (27). cAMP-elevating agents can promote preOLs lineage progression and differentiation but may inhibit their proliferation (17,28,29). Although mature oligodendrocytes are more resistant to hypoxic-ischemic injury than preOLs (6 -9), rolipram treatment may in fact deplete the number of proliferating preOLs after hypoxicischemic injury, as demonstrated in our study.…”

Section: Discussionsupporting

confidence: 62%

Rolipram, a Phosphodiesterase Type IV Inhibitor, Exacerbates Periventricular White Matter Lesions in Rat Pups

et al. 2008

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Periventricular white matter injury is the leading cause of cerebral palsy in premature infants for which no effective treatments are available. Our previous studies have demonstrated that pharmacological activation of the cAMP response element-binding protein (CREB) signaling pathway, before hypoxic-ischemia protected against neuronal injury in neonatal rats. We examined whether rolipram, a phosphodiesterase type IV inhibitor, treatment after hypoxic-ischemia is protective against white matter injury in neonatal rats. Rats were exposed to hypoxia-ischemia (HI) on P7 and then treated with daily injections of various doses of rolipram (P7-P11). Immunohistochemical staining for myelin basic protein, ED1, glial fibrillary acidic protein, CREB and O1 were examined on P11. We found that the periventricular white matter and deep cortical lesions were exacerbated by rolipram administration after HI injury. The lesions in the rolipram-treated group also showed increased astrogliosis and increased CREB phosphorylation in the activated microglia and astrocytes. Furthermore, the rolipram-posttreated HI group had markedly depleted preoligodendrocytes in the ipsilateral hemisphere, which may be related to decreased preoligodendrocytes proliferation after rolipram treatment per se. These data suggest that rolipram treatment after hypoxic-ischemia is not protective; in contrast, rolipram may exacerbate hypoxic-ischemic white matter injury in neonatal rat brains. N early 90% of low-birth weight infants now survive with the advances in neonatal intensive care. Of the survivors, however, 10 -15% have cerebral palsy, and 25-50% have manifest cognitive and behavioral deficits (1). Periventricular white matter injury, or leukomalacia (PVL), is the major form of brain injury in preterm babies. The neuropatholgical findings are characterized by distinct cystic white matter lesions and, commonly, a more diffuse loss of white matter volume and secondary ventriculomegaly (2). Notably, despite the significant long-term morbidity, there is currently no specific treatment for these disorders.Although, the exact cause of PVL in human infants is currently unknown, hypoxia-ischemia (HI) is believed to be a significant cause (3). Cell-type specific factors are also likely to underlie the mechanisms of PVL. Data from a recent study demonstrated that PVL in humans was related to oxidative damage that particularly targeted cells of the oligodendrocyte lineage; whereas neuronal and glial cells were markedly more resistant (4). The timing of appearance of preoligodendrocytes (preOLs) coincides with the high-risk period for PVL (5). Considerable data demonstrate that preOLs are highly susceptible to oxidative stress and hypoxic-ischemia injury (6 -9). Compared with mature oligodendrocytes, preOLs express lower levels of antioxidant enzymes (6). These data suggest that acceleration of preOLs maturation might be a feasible strategy to reduce the severity of PVL.cAMP plays an important role in inducing oligodendrocyte differentiation and myeli...

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Section: Discussionsupporting

confidence: 62%

Rolipram, a Phosphodiesterase Type IV Inhibitor, Exacerbates Periventricular White Matter Lesions in Rat Pups

et al. 2008

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“…We showed that T3 continues to accelerate the morphological and functional maturation of postmitotic oligodendrocytes, indicating that the rate of oligodendrocyte maturation and the rate of progenitor cell proliferation are regulated independently by T3. Interestingly, cyclic AMP that affects progenitor cells proliferation and oligodendrocyte maturation has been shown to influence independently these two cAMP-regulated events (Raible and McMorris, 1993). Furthermore, retinoic acid which blocks the proliferation of oligodendrocyte progenitor cells has no effect on the maturation of oligodendrocytes (Laeng et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Oligodendrocyte maturation and progenitor cell proliferation are independently regulated by thyroid hormone

Baas¹,

Bourbeau²,

Sarliève³

et al. 1997

Glia

160

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“…Therefore, to analyze the effects of polyamines, mixed glial cell cultures were maintained in serum-free media for 48 hours prior to polyamine addition. Immunohistochemical analysis of cells maintained in 8 well chamber slides was performed as previously described (Raible and McMorris 1993, Sperber et al 2001). The total cell number and percentages of oligodendrocytes were identified as cells immunoreactive for 2',3' cyclic nucleotide phosphodiesterase (CNP) per total hematoxylin-labeled nuclei in culture.…”

Section: Methodsmentioning

confidence: 99%

LPS-induced CCL2 expression and macrophage influx into the murine central nervous system is polyamine-dependent

Puntambekar¹,

Davis²,

Hawel³

et al. 2011

Brain, Behavior, and Immunity

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Increased polyamine production is observed in a variety of chronic neuroinflammatory disorders, but in vitro and in vivo studies yield conflicting data on the immunomodulatory consequences of their production. Ornithine decarboxylase (ODC) is the rate-limiting enzyme in endogenous polyamine production. To identify the role of polyamine production in CNS-intrinsic inflammatory responses, we defined CNS sites of ODC expression and the consequences of inhibiting ODC in response to intracerebral injection of LPS+/− IFNγ. In situ hybridization analysis revealed that both neurons and non-neuronal cells rapidly respond to LPS+/− IFNγ by increasing ODC expression. Inhibiting ODC by co-injecting DFMO decreased LPS-induced CCL2 expression and macrophage influx into the CNS, without altering LPS-induced microglial or macrophage activation. Conversely, intracerebral injection of polyamines was sufficient to trigger macrophage influx into the CNS of wild-type but not CCL2KO mice, demonstrating the dependence of macrophage influx on CNS expression of CCL2. Consistent with these data, addition of putrescine and spermine to mixed glial cultures dramatically increased CCL2 expression and to a much lesser extent, TNF expression. Addition of all three polyamines to mixed glial cultures also decreased the numbers and percentages of oligodendrocytes present. However, in vivo, inhibiting the basal levels of polyamine production was sufficient to induce expression of apolipoprotein D, a marker of oxidative stress, within white matter tracts. Considered together, our data indicate that: (1) CNS-resident cells including neurons play active roles in recruiting pro-inflammatory TREM1+ macrophages into the CNS via polyamine-dependent induction of CCL2 expression and (2) modulating polyamine production in vivo may be a difficult strategy to limit inflammation and promote repair due to the dual homeostatic and pro-inflammatory roles played by polyamines.

show abstract

Oligodendrocyte differentiation and progenitor cell proliferation are independently regulated by cyclic AMP

Cited by 47 publications

References 24 publications

Rolipram, a Phosphodiesterase Type IV Inhibitor, Exacerbates Periventricular White Matter Lesions in Rat Pups

Rolipram, a Phosphodiesterase Type IV Inhibitor, Exacerbates Periventricular White Matter Lesions in Rat Pups

Oligodendrocyte maturation and progenitor cell proliferation are independently regulated by thyroid hormone

LPS-induced CCL2 expression and macrophage influx into the murine central nervous system is polyamine-dependent

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