myelin-basic-protein and Weight-Gain

Cognitive impairment is a common outcome for stroke survivors. Growth hormone (GH) could represent a potential therapeutic option as this peptide hormone has been shown to improve cognition in various clinical conditions. In this study, we evaluated the effects of peripheral administration of GH at 48 hours poststroke for 28 days on cognitive function and the underlying mechanisms.. Experimental stroke was induced by photothrombotic occlusion in young adult mice. We assessed the associative memory cognitive domain using mouse touchscreen platform for paired-associate learning task. We also evaluated neural tissue loss, neurotrophic factors, and markers of neuroplasticity and cerebrovascular remodeling using biochemical and histology analyses.. Our results show that GH-treated stroked mice made a significant improvement on the paired-associate learning task relative to non-GH-treated mice at the end of the study. Furthermore, we observed reduction of neural tissue loss in GH-treated stroked mice. We identified that GH treatment resulted in significantly higher levels of neurotrophic factors (IGF-1 [insulin-like growth factor-1] and VEGF [vascular endothelial growth factor]) in both the circulatory and peri-infarct regions. GH treatment in stroked mice not only promoted protein levels and density of presynaptic marker (SYN-1 [synapsin-1]) and marker of myelination (MBP [myelin basic protein]) but also increased the density and area coverage of 2 major vasculature markers (CD31 and collagen-IV), within the peri-infarct region.. These findings provide compelling preclinical evidence for the usage of GH as a potential therapeutic tool in the recovery phase of patients after stroke.

Topics: Animals; Association Learning; Brain; Cerebrovascular Circulation; Cognition; Collagen Type IV; Growth Hormone; Insulin-Like Growth Factor I; Male; Mice; Myelin Basic Protein; Neuronal Plasticity; Platelet Endothelial Cell Adhesion Molecule-1; Random Allocation; Stroke; Synapsins; Vascular Endothelial Growth Factor A; Vascular Remodeling; Weight Gain

Neuropeptide Y (NPY) is expressed in the developing central nervous system, however, its role in the brain development remains unclear. In this study, C57/B6 mice were intraperitoneally administered 1 nmol/capita/day of NPY, 10 nmol/capita/day of an NPY-receptor 1-specific antagonist (Y1R-A), or NPY and Y1R-A simultaneously (NPY+Y1R-A) from postnatal day (P) 7 to P14. Recombinant NPY reached the P14 cerebrum in 1 hour. These treatments didn't significantly affect body weight gain or P14 brain weight. The ratio of myelinated axons to total axons in the parietal cerebrum was significantly higher in the NPY group than in the control group. The expression of myelin basic protein (MBP)-mRNA in the cerebrum was significantly higher in the NPY group than in the control group and was significantly lower in the NPY+Y1R-A group than in the NPY group, while it was significantly higher in the NPY+Y1R-A group than in the control group. In cultured oligodendroglioma-derived B12 cells, NPY didn't influence the MBP-mRNA expression, while neurotrophin 3 (NT3) increased MBP mRNA via receptor-type tyrosine kinase type C (Trk C). NPY administration significantly increased NT3-mRNA expression in the P14 cerebrum as deduced by quantitative real-time PCR. The change in phosphorylated Trk C (P-Trk C) was proportional to that of the NT3-mRNA expression, and the proportion of P-Trk C was higher in the NPY group than in the control group. These results suggest that NPY, partially via Y1R, induces NT3 which, via Trk C phosphorylation, accelerates myelination by oligodendrocytes in the mouse brain during the neonatal period.

Topics: Animals; Animals, Newborn; Cell Line, Transformed; Cerebrum; Embryo, Mammalian; Gene Expression Regulation, Developmental; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Myelin Basic Protein; Myelin Sheath; Neuropeptide Y; Neurotrophin 3; Organogenesis; Receptor, trkC; Receptors, Neuropeptide Y; RNA, Messenger; Tyrosine; Weight Gain

In order to elucidate molecular mechanisms underlying brain dysfunction in offspring exposed to ethanol in utero, subclinical doses of ethanol that do not have apparent structural effect on the offspring were administered intraperitoneally to pregnant rats at various gestational stages. We measured the activity of membrane marker enzymes and the level of mRNA of myelin proteins of the offspring brain. The activity of a myelin specific enzyme, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) decreased in ethanol-exposed offspring. This effect was not related to the period of gestation or the dose of ethanol. Perikaryonal enzymes, acetylcholinesterase and Na+, K(+)-ATPase, were significantly affected in groups exposed to ethanol at early fetal stage and in high doses. Expression of mRNAs of CNP and myelin basic proteins decreased significantly in the ethanol-treated group, with abnormal developmental profile suggesting a relationship with delayed myelination in offspring exposed to ethanol in utero. The present findings suggest that in spite of the low doses of ethanol that do not cause clinical symptoms in the offspring, prenatal exposure to ethanol affects the level of mRNA of membrane enzyme proteins in the offspring brain, consequently causing a corresponding reduction in enzyme activity, that may lead to neuronal dysfunction. In a separate study, blood ethanol levels were found to reach a maximum level within 30 min after injection and be undetectable after 5 to 10 h. No accumulation effects due to daily injection were observed.

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Acetylcholinesterase; Animals; Brain; Cell Membrane; Ethanol; Female; Kinetics; Myelin Basic Protein; Neurons; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; RNA, Messenger; Sodium-Potassium-Exchanging ATPase; Weight Gain