Potential anti neuro-inflammatory effect of BioCen-128 in animal models of dementia.

BACKGROUND: BioCen-128 is a new active pharmaceutical ingredient composed of a specific bovine thymic fraction of a polypeptide nature. Positive results of similar thymus extracts have been shown to be effective in delaying the processes associated with aging, immunosenescence and Alzheimer's disease (AD), where the inflammation plays an important role. Because of the anti-inflammatory potential of BioCen-128, the aim of this study was to evaluate the granuloma model induced by a cotton wool implantation and the model induced by intracerebroventricular (ICV) administration of streptozotocin (STZ). METHOD: The experiment was carried out using male OF-1cenp mice weighing 20 ± 2 g. RESULTS: Mice administered BioCen-128 in via the IP route at 5, 10 and 20 mg/kg of corporal weigh showed a decrease in the wet and dry weights of the granuloma, providing evidence of a systemic anti-inflammatory effect. In the ICV model of STZ, the administration of BioCen-128 improved cognitive function. CONCLUSION: These responses suggested an anti-neuroinflammatory effect explainable by the action of thymosin ß4 and thymosin alfa proteins. The results suggested that BioCen-128 could be used in the prevention and treatment of some diseases, for example AD, where neuroinflammation is one of the biological events that take place.

Age-Related Changes in the Behavior of Apolipoprotein E Knockout Mice.

The knockout mouse model, B6.129P2-Apoetm1Unc is homozygotic for the Apolipoprotein E (ApoE) deletion; thus, it is capable of developing hyperlipidemia and atherosclerosis but ApoE is also a lipid-transport protein abundantly expressed in most neurons in the central nervous system, so these animals could also be models of neurodegenerative diseases. The aim of this study was to determine age-related changes in spontaneous behavior and in learning and memory of Apolipoprotein E knockout mice. Spontaneous behavioral measurements included sleeping pattern, motor coordination and balance by rotarod and open field activity, whereas learning and memory tests included forced alternation in Y-maze, novel object recognition and passive avoidance conditioning. Significant behavioral differences between aged knockout mice and age-matched wild type strain, C57Bl/6 were found in all the behavioral tests, except for the rotarod test. Genetically' modified mice exhibited less huddling contact during sleeping, decreased locomotor activity in novel environments and in learning and memory deficits. These results are consistent with the cognitive impairment and memory loss seen as the earliest clinical symptoms in neurodegenerative disorders such as Alzheimer's disease. The ApoE knockout mice might therefore be an appropriate model for studying the underlying mechanisms involved in behavioral changes caused by neurodegenerative diseases as well as for evaluating new therapies for these pathologies.

Antinociception produced by Thalassia testudinum extract BM-21 is mediated by the inhibition of acid sensing ionic channels by the phenolic compound thalassiolin B.

BACKGROUND: Acid-sensing ion channels (ASICs) have a significant role in the sensation of pain and constitute an important target for the search of new antinociceptive drugs. In this work we studied the antinociceptive properties of the BM-21 extract, obtained from the sea grass Thalassia testudinum, in chemical and thermal models of nociception in mice. The action of the BM-21 extract and the major phenolic component isolated from this extract, a sulphated flavone glycoside named thalassiolin B, was studied in the chemical nociception test and in the ASIC currents of the dorsal root ganglion (DRG) neurons obtained from Wistar rats. RESULTS: Behavioral antinociceptive experiments were made on male OF-1 mice. Single oral administration of BM-21 produced a significant inhibition of chemical nociception caused by acetic acid and formalin (specifically during its second phase), and increased the reaction time in the hot plate test. Thalassiolin B reduced the licking behavior during both the phasic and tonic phases in the formalin test. It was also found that BM-21 and thalassiolin B selectively inhibited the fast desensitizing (τ < 400 ms) ASIC currents in DRG neurons obtained from Wistar rats, with a nonsignificant action on ASIC currents with a slow desensitizing time-course. The action of thalassiolin B shows no pH or voltage dependence nor is it modified by steady-state ASIC desensitization or voltage. The high concentration of thalassiolin B in the extract may account for the antinociceptive action of BM-21. CONCLUSIONS: To our knowledge, this is the first report of an ASIC-current inhibitor derived of a marine-plant extract, and in a phenolic compound. The antinociceptive effects of BM-21 and thalassiolin B may be partially because of this action on the ASICs. That the active components of the extract are able to cross the blood-brain barrier gives them an additional advantage for future uses as tools to study pain mechanisms with a potential therapeutic application.