Transduced PTD-BDNF fusion protein protects against beta amyloid peptide-induced learning and memory deficits in mice.

Brain-derived neurotrophic factor (BDNF) promotes the survival and differentiation of hippocampal, cortical, and basal forebrain cholinergic neurons. However, the efficacy of BDNF via peripheral (i.v.) administration is limited by the lack of transport of the neurotrophin through the blood-brain barrier (BBB) in vivo. The present study describes that the i.v. administered recombinant human BDNF (rhBDNF) conjugated with a protein transduction domain (PTD ) is able to survive and promote the growth of hippocampal neurons impaired by Abeta25-35 (10 microM) in vitro and transport through the BBB in vivo. The Morris water maze test indicated that the i.v. PTD-rhBDNF improved the spatial learning and memory of mice impaired by the aggregated Abeta25-35. The peripherally administered PTD-rhBDNF exhibited neuroprotective effects in brain and raise the possibility of delivery of the exogenous rhBDNF in treatment of the brain diseases.

[The effects of lidocaine and chronic stress on neurogenesis in the hippocampal dentate gyrus of adult mice].

OBJECTIVE: To evaluate the effects of chronic stress and lidocaine administration on the neurogenesis in the hippocampal dentate gyrus of adult mice. METHODS: Twenty-four adult mice were randomly divided into 3 equal groups: control group (Group C), chronic stress group (group S) and lidocaine group (group L). The duration of the experiment was fourteen days. During the experiment, animals of group C received daily NS intraperitoneal administration; group S received daily NS intraperitoneal administration and followed by a stimulation from variable chronic stressor each day; and Group L received daily intraperitoneal lidocaine administration before being stressed. At the end of the experiment, the mice were killed and their brain were taken out. Immunohistochemistry was use to detect the expression of Brall and brain-derived neurotrophic factor (BDNP) in the hippocampal dentate gyrus. The adrenal underwent pathological examination. RESULTS: Compared with group C, a significant decrease in number of bromodeoxyuridine immunoreactive was coincident with a significant decrease in number of BDNF immunoreactive cells in the dentate gyrus of group S, but there was no significant change in Group L. Chronic stress resulted in diffuse hyperplasia of the adrenal cortex and adrenal medulla atrophy, which suggested that stress-adaption failure of adrenal gland occurred, however, it didn't bring any significant pathologic changes on the adrenal gland of the mice pretreated with lidocaine. CONCLUSION: Chronic stress results in persistent inhibition of cell proliferation of the hippocampal dentate gyrus, while lidocaine can reverse the influence by regulating the growth factors and the adrenal steroid levels.

Inhibition by agmatine on morphine-induced conditioned place preference in rats.

Our previous studies demonstrated the ability of exogenous agmatine to inhibit tolerance to and physical dependence on morphine in mice, rats and monkeys. The present study further evaluated the effect of agmatine on the psychological dependence induced by morphine in conditioned place preference assay. Agmatine (0.75-20 mg/kg, s.c.) co-administered with morphine during the conditioning sessions completely abolished the acquisition of morphine-induced conditioned place preference in rats, which was associated with activation of imidazoline receptors. Agmatine (0.75-10 mg/kg, s.c.) administered on the test day inhibited the expression of the place preference. After 30 days of extinction of conditioned place preference, agmatine 2.5 and 40 mg/kg inhibited the priming effect of morphine 0.5 mg/kg on the place preference. Furthermore, agmatine inhibited the increased expression of FosB in the nucleus accumbens caused by chronic morphine. All these results suggest that agmatine could inhibit morphine-induced psychological dependence and relapses by affecting the expression of transcription factor FosB.