Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain

Neurons and glia are generated throughout adulthood from proliferating cells in two regions of the rat brain, the subventricular zone (SVZ) and the hippocampus. This study shows that exogenous basic fibroblast growth factor (FGF-2) and epidermal growth factor (EGF) have differential and site-specific effects on progenitor cells in vivo. Both growth factors expanded the SVZ progenitor population after 2 weeks of intracerebroventricular administration, but only FGF-2 induced an increase in the number of newborn cells, most prominently neurons, in the olfactory bulb, the normal destination for neuronal progenitors migrating from the SVZ. EGF, on the other hand, reduced the total number of newborn neurons reaching the olfactory bulb and substantially enhanced the generation of astrocytes in the olfactory bulb. Moreover, EGF increased the number of newborn cells in the striatum either by migration of SVZ cells or by stimulation of local progenitor cells. No evidence of neuronal differentiation of newborn striatal cells was found by three-dimensional confocal analysis, although many of these newborn cells were associated closely with striatal neurons. The proliferation of hippocampal progenitors was not affected by either growth factor. However, EGF increased the number of newborn glia and reduced the number of newborn neurons, similar to the effects seen in the olfactory bulb. These findings may be useful for elucidating the in vivo role of growth factors in neurogenesis in the adult CNS and may aid development of neuronal replacement strategies after brain damage

Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord

The existence of multipotent progenitor populations in the adult forebrain has been widely studied. To extend this knowledge to the adult spinal cord we have examined the proliferation, distribution, and phenotypic fate of dividing cells in the adult rat spinal cord. Bromodeoxyuridine (BrdU) was used to label dividing cells in 13- to 14-week-old, intact Fischer rats. Single daily injections of BrdU were administered over a 12 d period. Animals were killed either 1 d or 4 weeks after the last injection of BrdU. We observed frequent cell division throughout the adult rodent spinal cord, particularly in white matter tracts (5-7% of all nuclei). The majority of BrdU-labeled cells colocalized with markers of immature glial cells. At 4 weeks, 10% of dividing cells expressed mature astrocyte and oligodendroglial markers. These data predict that 0.75% of all astrocytes and 0.82% of all oligodendrocytes are derived from a dividing population over a 4 week period. To determine the migratory nature of dividing cells, a single BrdU injection was given to animals that were killed 1 hr after the injection. In these tissues, the distribution and incidence of BrdU labeling matched those of the 4 week post injection (pi) groups, suggesting that proliferating cells divide in situ rather than migrate from the ependymal zone. These data suggest a higher level of cellular plasticity for the intact spinal cord than has previously been observed and that glial progenitors exist in the outer circumference of the spinal cord that can give rise to both astrocytes and oligodendrocytes

Proliferation and Differentiation of Progenitor Cells Throughout the Intact Adult Rat Spinal Cord

The existence of multipotent progenitor populations in the adult forebrain has been widely studied. To extend this knowledge to the adult spinal cord we have examined the proliferation, distribution, and phenotypic fate of dividing cells in the adult rat spinal cord. Bromodeoxyuridine (BrdU) was used to label dividing cells in 13- to 14-week-old, intact Fischer rats. Single daily injections of BrdU were administered over a 12 d period. Animals were killed either 1 d or 4 weeks after the last injection of BrdU. We observed frequent cell division throughout the adult rodent spinal cord, particularly in white matter tracts (5-7% of all nuclei). The majority of BrdU-labeled cells colocalized with markers of immature glial cells. At 4 weeks, 10% of dividing cells expressed mature astrocyte and oligodendroglial markers. These data predict that 0.75% of all astrocytes and 0.82% of all oligodendrocytes are derived from a dividing population over a 4 week period. To determine the migratory nature of dividing cells, a single BrdU injection was given to animals that were killed 1 hr after the injection. In these tissues, the distribution and incidence of BrdU labeling matched those of the 4 week post injection (pi) groups, suggesting that proliferating cells divide in situ rather than migrate from the ependymal zone. These data suggest a higher level of cellular plasticity for the intact spinal cord than has previously been observed and that glial progenitors exist in the outer circumference of the spinal cord that can give rise to both astrocytes and oligodendrocytes

Periventricular white matter hyperintensities increase the likelihood of progression from amnestic mild cognitive impairment to dementia

BACKGROUND: White matter hyperintensities (WMH) have an effect on cognition and are increased in severity among individuals with amnestic mild cognitive impairment (aMCI). The influence of WMH on progression of aMCI to Alzheimer’s disease (AD) is less clear. METHODS: Data were drawn from a three-year prospective, double blind, placebo controlled clinical trial that examined the effect of donepezil or vitamin E on progression from aMCI to AD. WMH from multiple brain regions were scored on MR images obtained at entry into the trial from a subset of 152 study participants using a standardized visual rating scale. Cox proportional hazards models adjusting for age, education and treatment arm were used to investigate the role of WMH on time to progression. RESULTS: 55 of the 152 (36.2 %) aMCI subjects progressed to AD. Only periventricular hyperintensities (PVH) were related to an increased risk of AD within three years (HR = 1.59, 95 % CI = 1.24–2.05, p-value < 0.001). Correcting for medial temporal lobe atrophy or the presence of lacunes did not change statistical significance. CONCLUSION: PVH are associated with an increased risk of progression from aMCI to AD. This suggests that PVH, an MRI finding thought to represent cerebrovascular damage, contributes to AD onset in vulnerable individuals independent of Alzheimer pathology