Neuroscience
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Comparative Study
The role of different strain backgrounds in bacterial endotoxin-mediated sensitization to neonatal hypoxic-ischemic brain damage.
Genetic background is known to influence the outcome in mouse models of human disease, and previous experimental studies have shown strain variability in the neonatal mouse model of hypoxia-ischemia. To further map out this variability, we compared five commonly used mouse strains: C57BL/6, 129SVJ, BALB/c, CD1 and FVB in a pure hypoxic-ischemic setup and following pre-sensitization with lipopolysaccharide (LPS). Postnatal day 7 pups were subjected to unilateral carotid artery occlusion followed by continuous 30 min 8% oxygen exposure at 36 °C. ⋯ Finally, two of the four strongly affected strains--C57BL/6 and CD1--revealed pronounced contralateral astrogliosis with a neuroanatomical localization similar to that observed on the occluded hemisphere. Overall, the current findings demonstrate strain differences in response to hypoxia-ischemia alone, to stress associated with vehicle injection, and to LPS-mediated pre-sensitization, which partially explains the high variability seen in the neonatal mouse models of hypoxia-ischemia. These results can be useful in future studies of fetal/neonatal response to inflammation and reduced oxygen-blood supply.
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Opioid receptors, especially μ-opioid receptors, in the ventral tegmental area (VTA) and nucleus accumbens (NAcc) are reported to regulate food motivation. However, the roles of μ-, δ- and κ-opioid receptors are not fully understood. Moreover, since μ-, δ- and κ-opioid receptors are reported to distribute in the hypothalamus, these receptors in the hypothalamus might regulate feeding behavior. ⋯ The injection of β-FNA and naltrindole into the LH, but not the VTA or NAcc, decreased food intake. The injection of norBNI into the LH and VTA, but not the NAcc, decreased food intake. These results indicate that μ-, δ- and κ-opioid receptors in the LH play a more important role in the regulation of feeding behavior than those receptors in the VTA and the NAcc.
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Multiple sclerosis (MS) is a chronic, progressive demyelinating disorder which affects the central nervous system (CNS) and is recognized as the major cause of nervous system disability in young adults. Enhancing myelin repair by stimulating endogenous progenitors is a main goal in efforts for MS treatment. Fingolimod (FTY720) which is administrated as an oral medicine for relapsing-remitting MS has direct effects on neural cells. ⋯ FTY720 at doses 0.3 and 1mg/kg decreased the inflammation score at the site of LPC injection and decreased the extent of demyelination. FTY720 especially at the lower dose increased the number of remyelinated axons and newly produced myelinating cells. These data indicate that repetitive treatment with FTY720, behind an anti-inflammatory effect, exerts beneficial effects on the process of endogenous repair of demyelinating insults.
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Bone marrow mesenchymal stem cells (BMSCs) transplantation can ameliorate cognitive impairment in chronic ischemic brain injury, but the underlying mechanism is poorly understood. It is considered that the hippocampus holds the capabilities of memory consolidation and spatial navigation, and the gamma amino butyric acid (GABA)ergic system plays an important role in the control of learning and memory processes. Herein, we investigated whether transplantation of BMSCs could improve cognitive impairment via regulating the hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion. ⋯ Our results showed that the 2VO model presented decreased capacities of learning and memory and down-regulated the expression of GABA, GAD67 or GABA(B)R1 in the hippocampal CA1 subfield in comparison to the sham group (P<0.05), while administration of BMSCs (experimental group) manifested increased performances of learning sessions and probe tasks, as well as up-regulated expression of GABA, GAD67 or GABA(B)R1 compared with the control group I (P<0.05). Collectively, these findings suggest that transplantation of BMSCs is capable of improving cognitive impairment via up-regulating the hippocampal GABAergic system in a rat model of chronic cerebral hypoperfusion. Hence, BMSCs transplantation could serve as an important tool for cell therapy in chronic cerebral hypoperfusion disorders.
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Synapsins (Syns) are an evolutionarily conserved family of presynaptic proteins crucial for the fine-tuning of synaptic function. A large amount of experimental evidences has shown that Syns are involved in the development of epileptic phenotypes and several mutations in Syn genes have been associated with epilepsy in humans and animal models. Syn mutations induce alterations in circuitry and neurotransmitter release, differentially affecting excitatory and inhibitory synapses, thus causing an excitation/inhibition imbalance in network excitability toward hyperexcitability that may be a determinant with regard to the development of epilepsy. ⋯ These currents sustain the faster spiking in Syn-deficient cells by increasing the after hyperpolarization and limiting the Na(+) and Ca(2+) channel inactivation during repetitive firing. This in turn speeds up the depolarization phase by reaching the AP threshold faster. Our results provide evidence that Syn silencing increases intrinsic cell excitability associated with increased Ca(2+) and Ca(2+)-dependent BK currents in the absence of excitatory or inhibitory inputs.