Dietary restriction reduces hippocampal neurogenesis and granule cell neuron density without affecting the density of mossy fibers.

The hippocampal formation undergoes significant morphological and functional changes after prolonged caloric and dietary restriction (DR). In this study we tested whether prolonged DR results in deleterious alterations in hippocampal neurogenesis, density of granule cell neurons and mossy fibers, all of which support plasticity in the dentate gyrus. Young adult animals either experienced free access to food (control condition), or every-other-day feeding regimen (DR condition) for 3months. The number of Ki-67 cells and 28-day old 5-bromo-2'-deoxyuridine (BrdU) cells were quantified in the dorsal and ventral dentate gyrus to determine the effect of DR on cellular proliferation and survival of neural progenitor cells in the anatomically defined regions of the dentate gyrus. The density of granule cell neurons and synaptoporin were also quantified to determine the effect of DR on granule cell neurons and mossy fiber projections in the dentate gyrus. Our results show that DR increases cellular proliferation and concurrently reduces survival of newly born neurons in the ventral dentate gyrus without effecting the number of cells in the dorsal dentate gyrus. DR reduced density of granule cell neurons in the dorsal dentate gyrus. These alterations in the number of granule cell neurons did not affect mossy fiber density in DR animals, which was visualized as no differences in synaptoporin expression. Our findings demonstrate that granule cell neurons in the dentate gyrus are vulnerable to chronic DR and that the reorganization of granule cells in the dentate gyrus subregions is not producing concomitant alterations in dentate gyrus neuronal circuitry with this type of DR.

Staples MC ，Fannon MJ ，Mysore KK ，Dutta RR ，Ongjoco AT ，Quach LW ，Kharidia KM ，Somkuwar SS ，Mandyam CD ... -  《-》

[Neurogenesis of dentate granule cells following kainic acid induced seizures in immature rats].

Wang YL ，Sun RP ，Lei GF ，Wang JW ，Guo SH ... -  《-》

Inhibition of dentate granule cell neurogenesis with brain irradiation does not prevent seizure-induced mossy fiber synaptic reorganization in the rat.

Parent JM ，Tada E ，Fike JR ，Lowenstein DH ... -  《-》

Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice.

Lee J ，Duan W ，Mattson MP 《JOURNAL OF NEUROCHEMISTRY》

Examination of granule layer cell count, cell density, and single-pulse BrdU incorporation in rat organotypic hippocampal slice cultures with respect to culture medium, septotemporal position, and time in vitro.

Adult neurogenesis in the dentate gyrus is assuming an increasingly important role in supporting hippocampal-dependent learning and the modulation of mood and anxiety. Moreover, injury to the developing postnatal dentate gyrus has profound effects on neurogenesis and hippocampal learning throughout life. Organotypic hippocampal slice cultures represent an attractive model for studying neurogenesis both in the early postnatal and adult hippocampus, as they retain much of their anatomical and functional circuitry in vitro. Ongoing neurogenesis has been recently demonstrated in organotypic hippocampal slice cultures. However, cell proliferation, one of the critical components of neurogenesis, has yet to be characterized in this culture system. We examined single-pulse S-phase bromo-deoxyuridine (BrdU) labeling in the dentate granule layer with respect to the septotemporal position of origin of the slice culture, the medium the cultures were grown in, and the time the cultures were maintained in vitro up to 14 days, when they are believed to have matured to a near adult state. Using single 10-microm sections through a culture as our reference volume, we report significant effects of septotemporal position on the number of granule layer cells and the number of cells in S-phase, as estimated by short-survival (2 hours) BrdU studies. We report a declining rate of BrdU incorporation, evidence of significant structural changes within the granule cell layer, and differences in cell death between culture media over the first 14 days in vitro. We report caution with the use of BrdU cell density and changes in cell number to indirectly estimate proliferation.

Sadgrove MP ，Laskowski A ，Gray WP 《JOURNAL OF COMPARATIVE NEUROLOGY》