Cell Cycle Regulation in Retinal Progenitors by Glia-Derived Neurotrophic Factor and Docosahexaenoic Acid

Insua, María Fernanda; Garelli, Andrés; Rotstein, Nora P.; German, Olga Lorena; Arias, Andrés Hugo; Politi, Luis E.

doi:10.1167/iovs.02-0952

Cited by 46 publications

(49 citation statements)

References 52 publications

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“…Finally, different species were tested, which could be relevant, because the spontaneously hypertensive rats used by Dempsey and coworkers have a higher basal progenitor cell proliferation compared with normotensive rats. 18 GDNF also stimulates proliferation of other stem/progenitor cells, notably retinal progenitor cells in vitro, 19 and neural precursors from the embryonic gut. 20 Our data indicate that this effect is mediated by receptors on the stem/progenitor cells themselves.…”

Section: Discussionmentioning

confidence: 99%

Intracerebral Infusion of Glial Cell Line-Derived Neurotrophic Factor Promotes Striatal Neurogenesis After Stroke in Adult Rats

Kobayashi¹,

Ahlenius²,

Thored³

et al. 2006

Stroke

187

126

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Background and Purpose-Stroke triggers increased progenitor proliferation in the subventricular zone (SVZ) and the generation of medium spiny neurons in the damaged striatum of rodents. We explored whether intrastriatal infusion of glial cell line-derived neurotrophic factor (GDNF) promotes neurogenesis after stroke. Methods-Adult rats were subjected to 2-hour middle cerebral artery occlusion (MCAO). GDNF was infused into the ischemic striatum either during the first week after MCAO, with the animals being killed directly thereafter, or during the third and fourth weeks, with the rats being killed 1 week later. New cells were labeled with 5Ј-bromo-2Јdeoxyuridine (BrdU) on day 7 or during the second week, respectively. Neurogenesis was assessed immunocytochemically with antibodies against BrdU and neuronal, glial, or progenitor markers. GDNF receptor expression was analyzed in SVZ tissue and neurospheres by reverse transcription-polymerase chain reaction and immunocytochemistry. Results-GDNF infusion increased cell proliferation in the ipsilateral SVZ and the recruitment of new neuroblasts into the striatum after MCAO and improved survival of new mature neurons. The GDNF receptor GFR␣1 was upregulated in the SVZ 1 week after MCAO and was coexpressed with markers of dividing progenitor cells. Conclusions-Intrastriatal infusion of GDNF in the postischemic period promotes several steps of striatal neurogenesis after stroke, partly through direct action on SVZ progenitors. Because delivery of GDNF has biological effects in the human brain, our data suggest that administration of this factor may promote neuroregenerative responses in stroke patients.

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Section: Discussionmentioning

confidence: 99%

Intracerebral Infusion of Glial Cell Line-Derived Neurotrophic Factor Promotes Striatal Neurogenesis After Stroke in Adult Rats

Kobayashi¹,

Ahlenius²,

Thored³

et al. 2006

Stroke

187

126

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“…The dentate gyrus and associated hilus of the hippocampal formation showed a consistent increased thickness in proliferative zones, with a decreased size of target regions, which could reflect an inhibition or delay of neurogenesis, or disruption in postmitotic migration (27). Other recent studies have shown that DHA promotes cellcycle exit in retinal neuroprogenitor cells in culture (43) and promotes differentiation of neural stem cells into neurons by promoting cell-cycle exit and suppressing cell death (28). Restriction of (n-3) fatty acids leads to reduced DHA, increased (n-6) fatty acids, and increased dopamine in fetal brain cortex (44) and over-expression of dopamine receptor genes (45).…”

Section: Introductionmentioning

confidence: 87%

Dietary (n-3) Fatty Acids and Brain Development1

Innis

2007

The Journal of Nutrition

735

512

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“…Cultures from PN0 retinas treated at day 2 with or without RA showed similar percentages of BrdUpositive cells (Table 4). Since by day 2 few photoreceptor progenitors remain in the cell cycle, we added RA at day 0, when many progenitors still are proliferating 46 ; this addition decreased slightly, though not significantly, the percentage of BrdU-labeled cells compared to controls (Table 4).…”

Section: Ra Effect On Cell Cycle Exitmentioning

confidence: 99%

Retinoic Acid Promotes Apoptosis and Differentiation in Photoreceptors by Activating the P38 MAP Kinase Pathway

Genaro

Simón

Rotstein

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Retinoic acid (RA) has a critical role during development of the retina. We investigated RA effects on photoreceptor apoptosis and differentiation, and the intracellular pathways involved.METHODS. Rat retinal neuronal cultures were supplemented with RA with or without docosahexaenoic acid (DHA), a photoreceptor survival factor, and photoreceptor apoptosis and differentiation were evaluated at different times of development. To investigate the intracellular pathways activated by RA, the levels of phosphorylated (P) ERK and P-p38 in cultures with or without RA, and the effect of pretreatment with SB203580, a p38 specific inhibitor, on apoptosis and differentiation were evaluated.RESULTS. RA addition at day 0, when cells still were proliferating, selectively increased apoptosis in photoreceptors, whereas addition at day 2 no longer caused cell death. RA stimulated opsin and peripherin expression, and neurite outgrowth regardless of the time of development. Addition of RA at day 0, but not at day 2, rapidly increased P-p38 levels, but did not affect P-ERK levels. p38 inhibition completely prevented RA-induced apoptosis, and partially decreased differentiation. DHA prevented apoptosis and additively increased differentiation, without affecting RA activation of p38. CONCLUSIONS.Our results show that RA activation of the p38 intracellular pathway was essential for its early induction of apoptosis and partially responsible for promoting differentiation. DHA prevention of this apoptosis suggests that RA effects during early development must be counterbalanced by survival factors to prevent photoreceptor death, in an interplay that might help to establish the final number of photoreceptors.

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Cell Cycle Regulation in Retinal Progenitors by Glia-Derived Neurotrophic Factor and Docosahexaenoic Acid

Cited by 46 publications

References 52 publications

Intracerebral Infusion of Glial Cell Line-Derived Neurotrophic Factor Promotes Striatal Neurogenesis After Stroke in Adult Rats

Intracerebral Infusion of Glial Cell Line-Derived Neurotrophic Factor Promotes Striatal Neurogenesis After Stroke in Adult Rats

Dietary (n-3) Fatty Acids and Brain Development1

Retinoic Acid Promotes Apoptosis and Differentiation in Photoreceptors by Activating the P38 MAP Kinase Pathway

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