N for an increase in neurogenic activity at early time points

N for an increase in neurogenic activity at early time points after hypoglycemia is uncertain. Thus, we speculated that this transient increase of neurogenesis after seizure is related to synaptic release of zinc and cytolysis after dentate granule cell degeneration. Our present study demonstrates several zinc accumulating neurons in the dentate granule cell and hilar cell bodies after seizure. Previously we suggested that those zinc-accumulated neurons were degenerating after seizure [27]. We believe that continuous liberation of free zinc from the degenerating dentate granule cells or from mossy fiber synaptic terminals may chronically stimulate progenitor cell proliferation and support survival of neuroblast after hypoglycemia insult. Therefore, we tested the effects of zinc chelation on basal neurogenesis as well as on seizure-induced transient neurogenesis. Continuous treatment with CQ for 1 week without seizure significantly decreased basal progenitor cell proliferation in the hippocampus compared to the vehicle treatedZinc and Hippocampal Neurogenesis after Seizuregroup, with a parallel reduction in the number of neuroblasts. Moreover, 1 week of continuous treatment with CQ after seizure also substantially reduced progenitor cell proliferation in the hippocampus. These results suggest that zinc in the brain modulates neurogenesis after epilepsy. However, a major concern regarding the use of CQ is that this chelator is not entirely zinc specific, since CQ also can chelate other transitional metals in the brain such as copper and iron [23]. To verify our present finding that reduction of neurogenesis by CQ treatment is solely due to depletion of extracellular zinc we will need a more specific zinc chelator for the future study. Another concern is that CQ may not only act as a zinc chelator but also act as a zinc ionophore [49]. However, we speculate that CQ binds with 1531364 chelatable (or free) zinc in the extracellular space and in the intracellular area, which depresses brain zinc availability to support neurogenesis either in the basal setting or after seizure. To differentiate whether zinc chelation or zinc ionophore effect of CQ may cause counter neurogenesis alternatively we delivered N,N,N9,N9-tetrakis(2pyridylmethyl)ethylenediamine (TPEN) after seizure for 1 week. In the present study, we found that intracellular zinc chelator, TPEN, also significantly reduced seizure-induced neurogenesis.This finding is consistent with previous published study using cultured human neuronal precursor cells that TPEN treatment resulted in significant decrease in cellular proliferation [50]. Thus, these data suggest that zinc plays a role in neurogenesis and zinc chelation reduces brain injury-induced neurogenesis. Taken together, our present study demonstrates that vesicular zinc in the hippocampus modulates neurogenesis in the adult brain under physiological as well as pathological conditions. Elucidation of the [DTrp6]-LH-RH biological activity mechanisms involved in the zinc-mediated hippocampal neurogenesis warrant further investigations.AcknowledgmentsThe authors thank Aaron M. Hamby, University of California, Berkeley, for help with preparing the manuscript.Author ContributionsConceived and designed the experiments: JHK BGJ BYC LMK MS HKS SWS. MedChemExpress SPDP Performed the experiments: JHK BGJ 24272870 BYC LMK. Analyzed the data: MS. Contributed reagents/materials/analysis tools: HKS SWS. Wrote the paper: MS HKS SWS.
Colorectal cancer is the third most frequently diagnosed cancer in males and the sec.N for an increase in neurogenic activity at early time points after hypoglycemia is uncertain. Thus, we speculated that this transient increase of neurogenesis after seizure is related to synaptic release of zinc and cytolysis after dentate granule cell degeneration. Our present study demonstrates several zinc accumulating neurons in the dentate granule cell and hilar cell bodies after seizure. Previously we suggested that those zinc-accumulated neurons were degenerating after seizure [27]. We believe that continuous liberation of free zinc from the degenerating dentate granule cells or from mossy fiber synaptic terminals may chronically stimulate progenitor cell proliferation and support survival of neuroblast after hypoglycemia insult. Therefore, we tested the effects of zinc chelation on basal neurogenesis as well as on seizure-induced transient neurogenesis. Continuous treatment with CQ for 1 week without seizure significantly decreased basal progenitor cell proliferation in the hippocampus compared to the vehicle treatedZinc and Hippocampal Neurogenesis after Seizuregroup, with a parallel reduction in the number of neuroblasts. Moreover, 1 week of continuous treatment with CQ after seizure also substantially reduced progenitor cell proliferation in the hippocampus. These results suggest that zinc in the brain modulates neurogenesis after epilepsy. However, a major concern regarding the use of CQ is that this chelator is not entirely zinc specific, since CQ also can chelate other transitional metals in the brain such as copper and iron [23]. To verify our present finding that reduction of neurogenesis by CQ treatment is solely due to depletion of extracellular zinc we will need a more specific zinc chelator for the future study. Another concern is that CQ may not only act as a zinc chelator but also act as a zinc ionophore [49]. However, we speculate that CQ binds with 1531364 chelatable (or free) zinc in the extracellular space and in the intracellular area, which depresses brain zinc availability to support neurogenesis either in the basal setting or after seizure. To differentiate whether zinc chelation or zinc ionophore effect of CQ may cause counter neurogenesis alternatively we delivered N,N,N9,N9-tetrakis(2pyridylmethyl)ethylenediamine (TPEN) after seizure for 1 week. In the present study, we found that intracellular zinc chelator, TPEN, also significantly reduced seizure-induced neurogenesis.This finding is consistent with previous published study using cultured human neuronal precursor cells that TPEN treatment resulted in significant decrease in cellular proliferation [50]. Thus, these data suggest that zinc plays a role in neurogenesis and zinc chelation reduces brain injury-induced neurogenesis. Taken together, our present study demonstrates that vesicular zinc in the hippocampus modulates neurogenesis in the adult brain under physiological as well as pathological conditions. Elucidation of the mechanisms involved in the zinc-mediated hippocampal neurogenesis warrant further investigations.AcknowledgmentsThe authors thank Aaron M. Hamby, University of California, Berkeley, for help with preparing the manuscript.Author ContributionsConceived and designed the experiments: JHK BGJ BYC LMK MS HKS SWS. Performed the experiments: JHK BGJ 24272870 BYC LMK. Analyzed the data: MS. Contributed reagents/materials/analysis tools: HKS SWS. Wrote the paper: MS HKS SWS.
Colorectal cancer is the third most frequently diagnosed cancer in males and the sec.