Vascular endothelial growth factor induces brain erythropoietin expression?

To investigate whether the formation of vascular endothelial growth factor (VEGF) influences erythropoietin (EPO) expression in physiological conditions, we injected into the left lateral cerebral ventricle of the Mongolian gerbil an adeno-associated virus (AAV) vector capable of expressing the 165-amino-acid isoform of VEGF (VEGF165). Twelve and 18 days after AAV vector injection, the experimental animals were sacrificed and expression of EPO was evaluated through immunohistochemical analysis of both the hippocampus and the frontal cortex. We observed that VEGF165 induces EPO expression in the hippocampal pyramidal layers and in the frontal cortex of the gerbil, particularly after the 18th day following treatment with the vector, which suggests that VEGF165 could act as a hypoxic-like signal for EPO production. This finding could help to clarify the functional role of EPO and the molecular mechanisms by which VEGF might mediate its effects in the brain.

Long-term effects of high doses of nicotine on feeding behavior and brain nitric oxide synthase activity in female mice.

We studied the long-term effects of repeated doses of nicotine, causing dependence, 120 days after its withdrawal on feeding behavior and on brain nitric oxide (NO) formation in female mice. Nicotine dependence was induced by subcutaneous (s.c.) nicotine injection (2 mg/kg, four injections daily) for 14 days. Daily food intake was evaluated for the entire observational period (120 days). Moreover, 30, 60, and 120 days after nicotine withdrawal, we evaluated food intake, nitrite/nitrate levels, and nitric oxide synthase (NOS) activity and expression in the hypothalamus after food deprivation (24 h). In animals in which nicotine dependence was induced (NM), daily food intake was similar to that of controls (M). However, following food deprivation, NM mice showed i) a significant increase in food intake, ii) changes in weight gain and in hypothalamic nitrite/nitrate levels, and iii) enhancement of hypothalamic neuronal NOS (nNOS) activity. Results indicate that high doses of nicotine producing dependence induce long-term changes in feeding behavior consequent to food deprivation associated to alterations in the brain nitrergic system.

Hypericum perforatum attenuates nicotine withdrawal signs in mice.

RATIONALE: Hypericum perforatum is used as a natural antidepressant, and other antidepressants have been marketed to aid in smoking cessation. OBJECTIVE: We investigated the effects of an extract of Hypericum perforatum (Ph-50) on withdrawal signs produced by nicotine abstinence in mice. METHODS: Nicotine (2 mg/kg, four injections daily) was administered for 14 days to mice. Different doses of Ph-50 (125-500 mg/kg) were administered orally immediately after the last nicotine injection. In another experiment, Ph-50 (500 mg/kg) was orally administered in combination with nicotine, i) starting from day 8 until the end of the nicotine treatment period, or ii) during nicotine treatment and after nicotine withdrawal, or iii) immediately after the last nicotine injection. On withdrawal from nicotine, all animals were evaluated for locomotor activity and abstinence signs. RESULTS: The locomotor activity reduction induced by nicotine withdrawal was abolished by Ph-50, which also significantly and dose-dependently reduced the total nicotine abstinence score when injected after nicotine withdrawal. CONCLUSIONS: These data show that treatment with Hypericum perforatum attenuates nicotine withdrawal signs in mice. Further studies are necessary to test the possibility that it may be used for smoking cessation treatment in humans.

Erythropoietin prevents cognition impairment induced by transient brain ischemia in gerbils.

Erythropoietin has recently been studied for its role in the central nervous system (CNS). It has been shown to exert neuroprotective effects in different models of brain injury. We studied whether neuroprotective effects assessed from the reduction of neuronal loss after transient brain ischemia are associated to the preservation of learning ability. Recombinant human erythropoietin (0.5-25 U) was injected in the lateral cerebral ventricle of gerbils that are subjected to temporary (3 min) bilateral carotid occlusion. Post-ischemic histological evaluation of CA1 area neuronal loss and passive avoidance test were performed. Treatment with recombinant human erythropoietin significantly reduced delayed neuronal death in the CA1 area of the hippocampus and prevented cognition impairment in the passive avoidance test. These data indicate that recombinant human erythropoietin neuroprotective effects in brain ischemia are associated with the preservation of learning function.