Myrtus communis subsp. communis improved cognitive functions in ovariectomized diabetic rats.

AIM: The purpose of this study was to investigate the possible effects of Myrtus communis subsp. communis (MC) on cognitive impairment in ovariectomized diabetic rats. MATERIAL AND METHOD: Female Sprague-Dawley rats were divided into 5 groups consisting of 15 rats each; Control (C), Diabetes (D), Ovariectomy and diabetes (OVX + D), Ovariectomy, diabetes and donepezil (OVX + D + Don), Ovariectomy, diabetes and Myrtus communis subsp. communis (OVX + D + MC). Blood glucose measurements were made at the beginning and end of the experiments. The animals underwent the novel object recognition test (NORT) and their performance was evaluated. In hippocampal tissues; amyloid beta (Aß) and neprilysin levels, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) activities, polysialylated neural cell adhesion molecule (PSA-NCAM), α7 subunit of neuronal nicotinic acetylcholine receptor (α7-nAChR) and brain derived neurotrophic factor (BDNF) gene expressions were examined. RESULTS: Animals with ovariectomy and diabetes showed increased levels of blood glucose, AChE activity and Aß levels, and decreased neprilysin levels, ChAT activity, α7-nAChR, PSA-NCAM and BDNF gene expressions in parallel with a decrease in NORT performance score. On the other hand, in the MC-treated OVX + D group, there was a significant decrease observed in blood glucose levels and AChE activities while there was improvement in NORT performances and an increase in hippocampal ChAT activity, neprilysin levels, α7-nAChR, PSA-NCAM and BDNF expressions. CONCLUSION: These results suggest that MC extract could improve cognitive and neuronal functions with its anticholinesterase and antihyperglycemic properties.

Thalamocortical pathfinding defects precede degeneration of the reticular thalamic nucleus in polysialic acid-deficient mice.

The modification of the neural cell adhesion molecule (NCAM) with polysialic acid (polySia) is tightly linked to neural development. Genetic ablation of the polySia-synthesizing enzymes ST8SiaII and ST8SiaIV generates polySia-negative but NCAM-positive (II(-/-)IV(-/-)) mice characterized by severe defects of major brain axon tracts, including internal capsule hypoplasia. Here, we demonstrate that misguidance of thalamocortical fibers and deficiencies of corticothalamic connections contribute to internal capsule defects in II(-/-)IV(-/-) mice. Thalamocortical fibers cross the primordium of the reticular thalamic nucleus (Rt) at embryonic day 14.5, before they fail to turn into the ventral telencephalon, thus deviating from their normal trajectory without passing through the internal capsule. At postnatal day 1, a reduction and massive disorganization of fibers traversing the Rt was observed, whereas terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved caspase-3 staining indicated abundant apoptotic cell death of Rt neurons at postnatal day 5. Furthermore, during postnatal development, the number of Rt neurons was drastically reduced in 4-week-old II(-/-)IV(-/-) mice, but not in the NCAM-deficient N(-/-) or II(-/-)IV(-/-)N(-/-) triple knock-out animals displaying no internal capsule defects. Thus, degeneration of the Rt in II(-/-)IV(-/-) mice may be a consequence of malformation of thalamocortical and corticothalamic fibers providing major excitatory input into the Rt. Indeed, apoptotic death of Rt neurons could be induced by lesioning corticothalamic fibers on whole-brain slice cultures. We therefore propose that anterograde transneuronal degeneration of the Rt in polysialylation-deficient, NCAM-positive mice is caused by defective afferent innervation attributable to thalamocortical pathfinding defects.

Migration and multipotentiality of PSA-NCAM+ neural precursors transplanted in the developing brain.

By optimizing the previously described strategy for obtention of spheres enriched in PSA-NCAM+ precursors, we prepared PSA-NCAM-immunoselected cell populations from cerebral hemispheres of neonatal MBP-LacZ transgenic mice. These cells expressed Nestin, exhibited clonal expansion potential and formed spheres, which were initially enriched in PSA-NCAM+ cells but became enriched in GD3+ oligodendrocyte progenitors after 1 week in B104 contionned medium. One month after their periventricular transplantation into the brain of wild-type and/or shiverer newborn mice, cells from PSA-NCAM+ spheres exhibited a higher rostral migration potential than cells from GD3+ spheres, and clearly contributed to myelination in the olfactory bulb. In shiverer hosts, both sphere populations generated oligodendrocytes with similar myelination potential. In addition PSA-NCAM+ sphere cells generated GFAP+ astrocytes and NeuN+ neurons, depending on their site of insertion. These results evidence the high plasticity of newborn PSA-NCAM+ neural precursors and suggest that they are promising tools for cell therapy of CNS diseases, including myelin disorders.