Characterization of epidermal growth factor-induced dysplasia in the adult rat subventricular zone.

Epidermal growth factor (EGF) is a mitogen widely used when culturing adult neural stem cells in vitro. Although proliferative effects can also be observed in vivo, intracerebroventricular infusion of EGF has been found to counteract neuronal determination and promote glial differentiation instead. However, EGF receptor activation has different effects on the subventricular zone (SVZ) in mice and rats, possibly because of species differences in SVZ cell composition.

Cardiovascular fitness is associated with cognition in young adulthood.

During early adulthood, a phase in which the central nervous system displays considerable plasticity and in which important cognitive traits are shaped, the effects of exercise on cognition remain poorly understood. We performed a cohort study of all Swedish men born in 1950 through 1976 who were enlisted for military service at age 18 (N = 1,221,727). Of these, 268,496 were full-sibling pairs, 3,147 twin pairs, and 1,432 monozygotic twin pairs.

Stimulatory effects of thyroid hormone on brain angiogenesis in vivo and in vitro.

Thyroid hormone is critical for the proper development of the central nervous system. However, the specific role of thyroid hormone on brain angiogenesis remains poorly understood. Treatment of rats from birth to postnatal day 21 (P21) with propylthiouracil (PTU), a reversible blocker of triiodothyronine (T3) synthesis, resulted in decreased brain angiogenesis, as indicated by reduced complexity and density of microvessels.

Peripheral administration of GH induces cell proliferation in the brain of adult hypophysectomized rats.

IGF-I treatment has been shown to enhance cell genesis in the brains of adult GH- and IGF-I-deficient rodents; however, the influence of GH therapy remains poorly understood. The present study investigated the effects of peripheral recombinant bovine GH (bGH) on cellular proliferation and survival in the neurogenic regions (subventricular zone (SVZ), and dentate gyrus of the hippocampus), as well as the corpus callosum, striatum, parietal cortex, and piriform cortex. Hypopituitarism was induced in female rats by hypophysectomy, and the rats were supplemented with thyroxine and cortisone acetate.

Age-dependent regenerative responses in the striatum and cortex after hypoxia-ischemia.

Regenerative responses after hypoxia-ischemia (HI) were investigated in the immature (P9) and juvenile (P21) mouse striatum and cortex by postischemic 5-bromo-2-deoxyuridine labeling and phenotyping of labeled cells 4 weeks later. HI stimulated the formation of new cells in striatum and cortex in immature, growing brains (P9), but when brain growth was finished (P21) proliferation could be stimulated only in striatum, not in cortex. However, the relative increase was higher in P21 (460%) than P9 striatum (50%), though starting from a lower level at P21.

Bromodeoxyuridine and the detection of neurogenesis.

Bromodeoxyuridine (BrdU) is widely used for labeling dividing cells to determine their fate. In particular, the analysis of neurogenesis in the adult mammalian brain has made significant progress through the use of this technique. However; when using BrdU for labeling, there are several issues to consider in order to minimalize possible cytotoxicity or false-positive labeling.

Intravenous brain-derived neurotrophic factor enhances poststroke sensorimotor recovery and stimulates neurogenesis.

Background And Purpose: The discovery of spontaneous neuronal replacement in the adult brain has shifted experimental stroke therapies toward a combined approach of preventing neuronal cell death and inducing neuronal plasticity. Brain-derived neurotrophic factor (BDNF) was shown to induce antiapoptotic mechanisms after stroke and to reduce infarct size and secondary neuronal cell death. Moreover, in intact animals, BDNF is a potent stimulator of adult neurogenesis.

Less neurogenesis and inflammation in the immature than in the juvenile brain after cerebral hypoxia-ischemia.

The effects of hypoxia-ischemia (HI) on proliferation and differentiation in the immature (postnatal day 9) and juvenile (postnatal day 21) mouse hippocampus were investigated by injecting bromodeoxyuridine (50 mg/kg) daily for 7 days after the insult and evaluating the labeling 5 weeks after HI. Phenotypic differentiation was evaluated using NeuN, Iba1, APC, and S100beta as markers of neurons, microglia, oligodendrocytes, and astrocytes, respectively. The basal proliferation, in particular neurogenesis, was higher in the immature than in the juvenile hippocampus.

Direct stimulation of adult neural stem cells in vitro and neurogenesis in vivo by vascular endothelial growth factor.

Hypoxia as well as global and focal ischemia are strong activators of neurogenesis in the adult mammalian central nervous system. Here we show that the hypoxia-inducible vascular endothelial growth factor (VEGF) and its receptor VEGFR-2/Flk-1 are expressed in clonally-derived adult rat neural stem cells in vitro. VEGF stimulated the expansion of neural stem cells whereas blockade of VEGFR-2/Flk-1-kinase activity reduced neural stem cell expansion.

Decreased neurogenesis after cholinergic forebrain lesion in the adult rat.

Adult neurogenesis has been shown to be regulated by a multitude of extracellular cues, including hormones, growth factors, and neurotransmitters. The cholinergic system of the basal forebrain is one of the key transmitter systems for learning and memory. Because adult neurogenesis has been implicated in cognitive performance, the present work aims at defining the role of cholinergic input for adult neurogenesis by using an immunotoxic lesion approach.

Transient expression of doublecortin during adult neurogenesis.

During development of the central nervous system, expression of the microtubule binding protein doublecortin (DCX) is associated with migration of neuroblasts. In addition to this developmental role, expression of DCX remains high within certain areas of the adult mammalian brain. These areas, mainly the dentate gyrus and the lateral ventricle wall in conjunction with the rostral migratory stream and olfactory bulb, retain the capacity to generate new neurons into adulthood.

Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis.

Exposure to an enriched environment and physical activity, such as voluntary running, increases neurogenesis of granule cells in the dentate gyrus of adult mice. These stimuli are also known to improve performance in hippocampus-dependent learning tasks, but it is unclear whether their effects on neurogenesis are exclusive to the hippocampal formation. In this study, we housed adult mice under three conditions (enriched environment, voluntary wheel running and standard housing), and analysed proliferation in the lateral ventricle wall and granule cell neurogenesis in the olfactory bulb in comparison to the dentate gyrus.

Long-term survival and cell death of newly generated neurons in the adult rat olfactory bulb.

In the adult rat olfactory bulb, neurons are continually generated from progenitors that reside in the lateral ventricle wall. This study investigates long-term survival and cell death of newly generated cells within the adult olfactory bulb. After injecting rats at 2 months of age with 5-bromodeoxyuridine (BrdU), the newly generated cells were quantified over a period of 19 months.

Impaired adult neurogenesis in mice lacking the transcription factor E2F1.

During nervous system development the fate of neural stem cells-whether to undergo proliferation, differentiation, or apoptosis-is controlled by various signals, such as growth factors. Here, we demonstrate that the transcription factor E2F1, which is targeted by several signaling cascades that are activated by growth factors, is involved in neurogenesis in the adult brain. When analyzing the brains of E2F1-deficient mice, we found significantly decreased stem cell and progenitor division in the proliferative zones of the lateral ventricle wall and the hippocampus.

Is it all DNA repair? Methodological considerations for detecting neurogenesis in the adult brain.

Since the early 1960s, in vivo observations have shown the generation of new neurons from dividing precursor cells. Nevertheless, these experiments suffered from skepticism, suggesting that the prevailing labeling method, which incorporates tagged thymidine analogs, such as [3H]-thymidine or bromodeoxyuridine (BrdU), may not be detecting a proliferative event, but could rather mark DNA repair in postmitotic neurons. Even today many scientists outside the field are still skeptical, because the question of specificity for thymidine labeling has not been sufficiently answered.