Delta-secretase-cleaved Tau antagonizes TrkB neurotrophic signalings, mediating Alzheimer's disease pathologies.

BDNF, an essential trophic factor implicated in synaptic plasticity and neuronal survival, is reduced in Alzheimer's disease (AD). BDNF deficiency's association with Tau pathology in AD is well documented. However, the molecular mechanisms accounting for these events remain incompletely understood. Here we show that BDNF deprivation triggers Tau proteolytic cleavage by activating δ-secretase [i.e., asparagine endopeptidase (AEP)], and the resultant Tau N368 fragment binds TrkB receptors and blocks its neurotrophic signals, inducing neuronal cell death. Knockout of BDNF or TrkB receptors provokes δ-secretase activation via reducing T322 phosphorylation by Akt and subsequent Tau N368 cleavage, inducing AD-like pathology and cognitive dysfunction, which can be restored by expression of uncleavable Tau N255A/N368A mutant. Blocking the Tau N368-TrkB complex using Tau repeat-domain 1 peptide reverses this pathology. Thus, our findings support that BDNF reduction mediates Tau pathology via activating δ-secretase in AD.

S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

Spinster homolog 2 (SPNS2) is the membrane transporter of sphingosine-1-phosphate (S1P), and it participates in several physiologic processes by activating different S1P receptors (S1PRs). However, its functions in the nervous system remain largely unclear. We explored the important role of SPNS2 in the process of retinal morphogenesis using a spns2-deficient rat model. In the absence of the functional SPNS2 transporter, we observed progressively aggravating laminar disorganization of the epithelium at the postnatal stage of retinal development. Disrupted cell polarity, delayed cell-cycle exit of retinal progenitor cells, and insufficient migration of newborn neurons were proposed in this study as potential mechanisms accounting for this structural disorder. In addition, we analyzed the expression profiles of spns2 and s1prs, and proposed that SPNS2 regulated retinal morphogenesis by establishing the S1P level in the eye and activating S1PR3 signaling. These data indicate that SPNS2 is indispensable for normal retinal morphogenesis and provide new insights on the role of S1P in the developing retina using an established in vivo model.-Fang, C., Bian, G., Ren, P., Xiang, J., Song, J., Yu, C., Zhang, Q., Liu, L., Chen, K., Liu, F., Zhang, K., Wu, C., Sun, R., Hu, D., Ju, G., Wang, J. S1P transporter SPNS2 regulates proper postnatal retinal morphogenesis.

Polarized Macrophages Have Distinct Roles in the Differentiation and Migration of Embryonic Spinal-cord-derived Neural Stem Cells After Grafting to Injured Sites of Spinal Cord.

Spinal cord injury (SCI) frequently provokes serious detrimental outcomes because neuronal regeneration is limited in the central nervous system (CNS). Thus, the creation of a permissive environment for transplantation therapy with neural stem/progenitor cells (NS/PCs) is a promising strategy to replace lost neuronal cells, promote repair, and stimulate functional plasticity after SCI. Macrophages are important SCI-associated inflammatory cells and a major source of secreted factors that modify the lesion milieu. Here, we used conditional medium (CM) from bone marrow-derived M1 or M2 polarized macrophages to culture murine NS/PCs. The NS/PCs showed enhanced astrocytic versus neuronal/oligodendrocytic differentiation in the presence of M1- versus M2-CM. Similarly, cotransplantation of NS/PCs with M1 and M2 macrophages into intact or injured murine spinal cord increased the number of engrafted NS/PC-derived astrocytes and neurons/oligodendrocytes, respectively. Furthermore, when cotransplantated with M2 macrophages, the NS/PC-derived neurons integrated into the local circuitry and enhanced locomotor recovery following SCI. Interesting, engrafted M1 macrophages promoted long-distance rostral migration of NS/PC-derived cells in a chemokine (C-X-C motif) receptor 4 (CXCR4)-dependent manner, while engrafted M2 macrophages resulted in limited cell migration of NS/PC-derived cells. Altogether, these findings suggest that the cotransplantation of NS/PCs together with polarized macrophages could constitute a promising therapeutic approach for SCI repair.

Dynamics of ten-eleven translocation hydroxylase family proteins and 5-hydroxymethylcytosine in oligodendrocyte differentiation.

The ten-eleven translocation (TET) family of methylcytosine dioxygenases catalyze oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and promote DNA demethylation. Despite the abundance of 5hmC and TET proteins in the brain, little is known about their role in oligodendrocytes (OLs). Here, we analyzed TET expression during OL development in vivo and in vitro, and found that three TET family members possess unique subcellular and temporal expression patterns. Furthermore, the level of 5hmC exhibits dynamic changes during OL maturation, which implies that 5hmC modification may play a role in the expression of critical genes necessary for OL maturation. siRNA-mediated silencing of the TET family proteins in OLs demonstrated that each of the TET proteins is required for OL differentiation. However, based on their unique domain structures, we speculate that the three TET members may function by different mechanisms. In summary, we have established the temporal expression of TET proteins and the dynamic level of 5hmC during OL development and demonstrate that all three TET members are necessary for OL differentiation.

Expression of phospho-Ca(2+) /calmodulin-dependent protein kinase II in the pre-Bötzinger complex of rats.

The pre-Bötzinger complex (pre-BötC) in the ventrolateral medulla oblongata is a presumed kernel of respiratory rhythmogenesis. Ca(2+) -activated non-selective cationic current is an essential cellular mechanism for shaping inspiratory drive potentials. Ca(2+) /calmodulin-dependent protein kinase II (CaMKII), an ideal 'interpreter' of diverse Ca(2+) signals, is highly expressed in neurons in mediating various physiological processes. Yet, less is known about CaMKII activity in the pre-BötC. Using neurokinin-1 receptor as a marker of the pre-BötC, we examined phospho (P)-CaMKII subcellular distribution, and found that P-CaMKII was extensively expressed in the region. P-CaMKII-ir neurons were usually oval, fusiform, or pyramidal in shape. P-CaMKII immunoreactivity was distributed within somas and dendrites, and specifically in association with the post-synaptic density. In dendrites, most synapses (93.1%) examined with P-CaMKII expression were of asymmetric type, occasionally with symmetric type (6.9%), whereas in somas, 38.1% were of symmetric type. P-CaMKII asymmetric synaptic identification implicates that CaMKII may sense and monitor Ca(2+) activity, and phosphorylate post-synaptic proteins to modulate excitatory synaptic transmission, which may contribute to respiratory modulation and plasticity. In somas, CaMKII acts on both symmetric and asymmetric synapses, mediating excitatory and inhibitory synaptic transmission. P-CaMKII was also localized to the perisynaptic and extrasynaptic regions in the pre-BötC.

Different TLR4 expression and microglia/macrophage activation induced by hemorrhage in the rat spinal cord after compressive injury.

BACKGROUND: Hemorrhage is a direct consequence of traumatic injury to the central nervous system and may cause innate immune reactions including cerebral Toll-like receptor (TLR) 4 upregulation which usually leads to poor outcome in the traumatic brain injury. In spinal cord injury (SCI), however, how hemorrhage induces innate immune reaction in spinal parenchyma remains unknown. The present study aimed to see whether blood component and/or other factor(s) induce TLR4 and microglia/macrophages involved innate immune reactions in the rat spinal cord after traumatic injury. METHODS: Using the compressive SCI model of the rat, hemorrhage in the spinal cord was identified by hematoxylin-eosin staining. Microglia/macrophage activation, TLR4 expression, and cell apoptosis were investigated by immunohistochemistry. Nuclear factor (NF)-κB p50 level of the two segments of the cord was detected by western blotting assay. With carbon powder injection, blood origination of the hematoma was explored. The blood-spinal cord barrier (BSCB) states of the lesion site and the hematoma were compared with immunohistochemistry and tannic acid-ferric chloride staining. RESULTS: Histological observation found blood accumulated in the center of compression lesion site (epicenter) and in the hematoma approximately 1.5 cm away from the epicenter. TLR4 expression, microglia//macrophage activation, and subsequent apoptosis in the area of far-away hematoma were late and weak in comparison to that in epicenter. In addition, TLR4 positive microglia/macrophages appeared to be phagocytotic in the far-away hematoma more obviously than that in the epicenter. Injected carbon powder indicated that accumulated blood of the far-away hematoma originated from the bleeding of the lesion epicenter, and the BSCB around the hematoma was not compromised in the early phase. Accordingly, at 3 days post injury, NF-κB p50 was upregulated based on the similar levels of blood component hemoglobin, and cell apoptosis was obvious in the epicenter but not in the far-away hematoma. CONCLUSION: These data suggest that besides blood component, BSCB compromise and the extent of tissue injury contribute more to TLR4 and microglia/macrophage responses to the spinal cord hemorrhage. Therefore, the innate immune environment is a necessary consideration for the SCI therapy targeting TLR4 and microglia/macrophages.

The effect of Lycium barbarum on spinal cord injury, particularly its relationship with M1 and M2 macrophage in rats.

BACKGROUND: Our past researches suggested that L. barbarum exhibits direct neuroprotective and immune regulatory effects on the central nervous system, which are highly related to the events involved in the spinal cord injury, but not yet been investigated. Immune responses play an important role in the development of the pathology after secondary injury, particularly the M1 and M2 types of macrophage, on which special emphasis was laid in this study. METHODS: In our previous studies L. barbarum was administrated orally from 7 days before the injury to ensure a stabilized concentration in the blood. For clinical application, L. barbarum can only be administered after the injury. Therefore, both pre-injury and post-injury administration protocols were compared. In vivo and in vitro studies were conducted and analyzed immunohistochemically, including Western blotting. RESULTS: The lesion size in the pre-treated group was much larger than that in the post-treated group. To explain this difference, we first studied the effect of L. barbarum on astrocytes, which forms the glial scar encircling the lesion. L. barbarum did not significantly affect the astrocytes. Then we studied the effect of L. barbarum on microglia/macrophages, particularly the M1 and M2 polarization. After spinal cord injury, the deleterious M1 cells dominant the early period, whereas the beneficial M2 cells dominate later. We found that in the pre-treated group L. barbarum significantly enhanced the expression of M1 cells and suppressed that of M2 cells, while in the post-treated group LBP markedly promoted the activity of M2 cells. This explained the difference between the pre- and post-treated groups. CONCLUSIONS: Lycium barbarum has been wildly accepted to have beneficial effects in various central nervous system diseases. Our finding of deleterious effect of LBP administered at early period of spinal cord injury, indicates that its application should be avoided. The substantial beneficial effect of LBP when administered at later stage has an important impact for clinical application.

Synaptic relationship between somatostatin- and neurokinin-1 receptor-immunoreactive neurons in the pre-Bötzinger complex of rats.

The pre-Bötzinger complex (pre-BötC) in the ventrolateral medulla oblongata is critical for the generation of respiratory rhythm in mammals. Somatostatin (SST) and neurokinin 1 receptor (NK1R) immunoreactivity have been used as markers of the pre-BötC. SST immunoreactivity almost completely overlaps with small fusiform NK1R-immunoreactive (ir) neurons, the presumed rhythmogenic neurons, but not with large multipolar NK1R-ir neurons. Understanding the neurochemical characteristics, especially the synaptic relationship of SST/NK1R-ir neurons within the pre-BötC network is essential in providing cellular and structural bases for understanding their physiological significance. This work has not been documented so far. We found that SST immunoreactivity was highly expressed in terminals, somas, and primary dendrites in the pre-BötC. Besides the small fusiform neurons, a small population of medium-sized NK1R-ir neurons also colocalized with SST. Large NK1R-ir neurons were not SST-ir, but received somatostatinergic inputs. SST-ir terminals were glutamatergic or GABAergic, and synapsed with NK1R-ir neurons. Most of synapses between them were of the symmetric type, indicating their inhibitory nature. Asymmetric synapses were evident between SST-ir terminals and NK1R-ir dendrites, strongly suggesting an excitatory innervation from the presumed rhythmogenic neurons as these neurons are glutamatergic. We speculate that SST-mediated excitatory and inhibitory synaptic transmission onto NK1R-ir rhythmogenic and follower neurons synchronizes their activity to contribute to respiratory rhythmogenesis and control.

Early Blockade of TLRs MyD88-Dependent Pathway May Reduce Secondary Spinal Cord Injury in the Rats.

To determine the role of toll-like receptors (TLRs) myeloid differentiation factor 88 (MyD88) dependent pathway in the spinal cord secondary injury, compression injury was made at T8 segment of the spinal cord in adult male Sprague-Dawley rats. Shown by RT-PCR, TLR4 mRNA in the spinal cord was quickly elevated after compression injury. Intramedullary injection of MyD88 inhibitory peptide (MIP) resulted in significant improvement in locomotor function recovery at various time points after surgery. Meanwhile, injury area, p38 phosphorylation, and proinflammation cytokines in the injured spinal cord were significantly reduced in MIP-treated animals, compared with control peptide (CP) group. These data suggest that TLRs MyD88-dependent pathway may play an important role in the development of secondary spinal cord injury, and inhibition of this pathway at early time after primary injury could effectively protect cells from inflammation and apoptosis and therefore improve the functional recovery.

The protective effects of inosine against chemical hypoxia on cultured rat oligodendrocytes.

Inosine is a purine nucleoside and is considered protective to neural cells including neurons and astrocytes against hypoxic injury. However, whether oligodendrocytes (OLs) could also be protected from hypoxia by inosine is not known. Here we investigated the effects of inosine on primarily cultured rat OLs injured by rotenone-mediated chemical hypoxia, and the mechanisms of the effects using ATP assay, MTT assay, PI-Hoechst staining, TUNEL, and immunocytochemistry. Results showed that rotenone exposure for 24 h caused cell death and impaired viability in both immature and mature OLs, while pretreatment of 10 mM inosine 30 min before rotenone administration significantly reduced cell death and improved the viability of OLs. The same concentration of inosine given 120 min after rotenone exposure also improved viability of injured mature OLs. Immunocytochemistry for nitrotyrosine and cellular ATP content examination indicated that inosine may protect OLs by providing ATP and scavenging peroxynitrite for cells. In addition, immature OLs were more susceptible to hypoxia than mature OLs; and at the similar degree of injury, inosine protected immature and mature OLs differently. Quantitative real-time PCR revealed that expression of adenosine receptors was different between these two stages of OLs. These data suggest that inosine protect OLs from hypoxic injury as an antioxidant and ATP provider, and the protective effects of inosine on OLs vary with cell differentiation, possibly due to the adenosine receptors expression profile. As OLs form myelin in the central nervous system, inosine could be used as a promising drug to treat demyelination-involved disorders.

Nogo-66 inhibits the dye-coupling of astrocytic gap junctions in vitro.

Communication between astrocytes via the gap junction is crucial for maintaining homeostasis of the extra-neuronal microenvironment of the central nervous system. Dysfunction of astrocytic gap junctions is involved in many brain disorders. Our previous studies demonstrated a novel co-localization of Nogo-66 receptor at glial gap junctions in rat cerebellum and posterior pituitary. The present study was aimed at exploring whether Nogo-66 can modulate glial gap junctions in vitro. We confirmed the co-localization of Nogo-66 receptor with Cx43 in cultured astrocytes, and stimulated astrocytes with myelin extracts, or Nogo-66-Fc conditioned medium. Finally, we expressed and purified a functionally effective GST-Nogo-66 peptide. Lucifer yellow transfer assay was adopted to measure the gap junction permeability. The results showed that the spreading of Lucifer yellow was inhibited significantly by all three treatments as compared with their corresponding controls. Therefore, this study shows a novel inhibitory effect of Nogo-66 on the permeability of astrocytic gap junctions, suggesting a presumable role of Nogo-66 receptor in modulating the glial gap junction.

Beneficial effect of the traditional chinese drug shu-xue-tong on recovery of spinal cord injury in the rat.

Shu-Xue-Tong (SXT) is a traditional Chinese drug widely used to ameliorate stagnation of blood flow, such as brain or myocardial infarction. Whether SXT may have therapeutic value for spinal cord injury (SCI), during which ischemia plays an important role in its pathology, remains to be elucidated. We hypothesized that SXT may promote SCI healing by improving spinal cord blood flow (SCBF), and a study was thus designed to explore this possibility. Twenty-five male Sprague-Dawley rats were used. SCI was induced by compression, and SXT was administrated 24 h postinjury for 14 successive days. The effects of SXT were assessed by means of laser-Doppler flowmetry, motor functional analysis (open-field walking and footprint analysis), and histological analysis (hematoxylin-eosin and thionin staining and NeuN immunohistochemistry). SXT significantly promoted SCBF of the contused spinal cord and enhanced the recovery of motor function. Histological analysis indicated that the lesion size was reduced, the pathological changes were ameliorated, and more neurons were preserved. Based on these results we conclude that SXT can effectively improve SCI.

Decreased neural stem/progenitor cell proliferation in mice with chronic/nonremitting experimental autoimmune encephalomyelitis.

It has been reported that autoimmune inflammatory processes in human multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), may induce an alteration in neurogenesis. Studies with transgenic EAE mice have demonstrated an enhancement of neurogenesis in the subventricular zone (SVZ). In contrast, a reduction of stem cell proliferation in the same region has been observed by Pluchino et al. [Brain 2008;131:2564-2578] in myelin oligodendrocyte glycoprotein (MOG)-induced EAE mice. We immunized female C57BL/6 mice with MOG 35-55 peptide and successfully developed chronic/nonremitting EAE, which is believed to be analogous to the progressive form of MS. On day 21 postimmunization, coronal brain sections were collected and stained with anti-5-bromo-2'-deoxyuridine (BrdU) antibody. By counting the number of BrdU-labeled cells, we demonstrated that the neural stem/progenitor cell (NSC/NPC) proliferation decreased in the SVZ, which basically confirms the study of Pluchino et al. on the changes in the SVZ. A reduction of NSC/NPC proliferation also occurred in the hippocampal subgranular zone of the dentate gyrus. The hippocampus is well known to be an important region involved in learning and memory; thus, our finding may offer a possible explanation for the cognitive impairment in human chronic MS.

Evidence for heterogeneity of astrocyte de-differentiation in vitro: astrocytes transform into intermediate precursor cells following induction of ACM from scratch-insulted astrocytes.

Our previous study definitely demonstrated that the mature astrocytes could undergo a de-differentiation process and further transform into pluripotential neural stem cells (NSCs), which might well arise from the effect of diffusible factors released from scratch-insulted astrocytes. However, these neurospheres passaged from one neurosphere-derived from de-differentiated astrocytes possessed a completely distinct characteristic in the differentiation behavior, namely heterogeneity of differentiation. The heterogeneity in cell differentiation has become a crucial but elusive issue. In this study, we show that purified astrocytes could de-differentiate into intermediate precursor cells (IPCs) with addition of scratch-insulted astrocyte-conditioned medium (ACM) to the culture, which can express NG2 and A2B5, the IPCs markers. Apart from the number of NG2(+) and A2B5(+) cells, the percentage of proliferative cells as labeled with BrdU progressively increased with prolonged culture period ranging from 1 to 10 days. Meanwhile, the protein level of A2B5 in cells also increased significantly. These results revealed that not all astrocytes could de-differentiate fully into NSCs directly when induced by ACM, rather they generated intermediate or more restricted precursor cells that might undergo progressive de-differentiation to generate NSCs.

Thymosin-beta4 attenuates ethanol-induced neurotoxicity in cultured cerebral cortical astrocytes by inhibiting apoptosis.

Thymosin-beta4 (Tbeta4) is a major actin monomer-binding peptide in mammalian tissues and plays a crucial role in the nervous system in synaptogenesis, neuronal survival and migration, axonal growth, and plastic changes of dendritic spines. However, it is unknown whether Tbeta4 is also involved in challenges with external stress such as ethanol-induced neurotoxicity. In the present study, we investigated the effects of Tbeta4 on ethanol-induced neurotoxicity in cultured cerebral cortical astrocytes and the underlying mechanisms. Primarily cultured astrocytes were treated with 1 microg/ml Tbeta4 2 h prior to administration of 100 mM ethanol for 0.5, 1, 3 and 6 days, respectively. The results showed that ethanol caused neurotoxicity in cultured astrocytes, as shown by declined cell viability, distinct astroglial apoptosis and increased intracellular peroxidation. Tbeta4 markedly promoted cell viability, ameliorated the injury of intracellular glial fibrillary acidic protein-immunopositive cytoskeletal structures, reduced the percentage of apoptotic astrocyte and cellular DNA fragmentation, suppressed caspase-3 activity and upregulated Bcl-2 expression, inhibited the accumulation of reactive oxygen species and production of malondialdehyde in ethanol-treated astrocytes in a time-dependent manner. These data indicated that Tbeta4 attenuates ethanol-induced neurotoxicity in cultured cortical astrocytes through inhibition of apoptosis signaling, and one of the mechanisms underlying the capacity of Tbeta4 to suppress apoptosis may in part be due to its effect of anti-peroxidation.

Long-term primary culture of highly-pure rat embryonic hippocampal neurons of low-density.

In order to develop a simplified method for long-term primary culture of highly-pure rat embryonic hippocampal neurons of low-density (10(3) cells/cm(2)), we optimized and modified conventional culturing methods. The modifications of our simplified method include: (1) combinational application of two growth substrates, tail collagen and poly-L-lysine, to coat plastic culture dishes and coverslips for a better neuronal attachment; (2) dissociation of hippocampal tissues with combinational use of two milder enzymes (collagenase and dispase) and trypsin of a lower concentration to minimize enzymatic damages to cultured neurons; (3) a cell pre-plating step to preliminarily eliminate the contaminating non-neuronal cells; (4) a modified culture medium as a critical step to promote highly pure neurons of low-density for a long term; and (5) appropriately reduced frequency and volume of refreshment of the culture medium. Using our modified method, the beta-tubulin III-immunostained and Hoechst 33342 counterstained neurons harvested a steady and healthy growth with a longer culture time of over 35 days, and a clear distinction between TAU-1- and MAP2-immunoreactive neurites was apparent at the early culturing period. In addition, the purity of neurons was over 95% at the different time points in comparison with the control culture using conventional serum-free method in which most neurons degenerated and died within 5 days. Thus, our modified method proved to be a simple, feasible as well as time- and resource-saving approach for a long-term survival of pure rat embryonic hippocampal neurons of low-density.

Time-dependent changes in learning ability and induction of long-term potentiation in the lithium-pilocarpine-induced epileptic mouse model.

To explore the mechanism underlying the development of learning deficits in patients with epilepsy, we generated a mouse model for temporal lobe epilepsy by intraperitoneally injecting mice with pilocarpine with lithium chloride, and investigated time-dependent changes in both contextual fear memory of those model mice and long-term potentiation (LTP) in hippocampal CA1 neurons 1 day, 2 weeks, and 6 weeks after the onset of status epilepticus (SE). Fear memory formation did not change 1 day and 2 weeks after the onset of SE, but was significantly reduced after 6 weeks. Induction of LTP was enhanced 1 day after the onset of SE, but returned to the normal level 2 weeks later, and was almost completely attenuated after 6 weeks. The enhancement of LTP was accompanied by an increase in output responses of excitatory postsynaptic potentials, whereas suppression of LTP was accompanied by alteration of the ratio of paired pulse facilitation. These results indicate that time-dependent changes of LTP induction have a causal role in the development of learning deficits of epilepsy patients.

Transcription factor RBP-J-mediated signaling represses the differentiation of neural stem cells into intermediate neural progenitors.

Notch signaling is critical for multiple aspects of neurogenesis, but how it regulates the proliferation and differentiation of neural stem cells (NSCs) and intermediate neural progenitors (INPs) has not been well elucidated, especially in vivo. In this study, we conditionally ablated the transcription factor RBP-J, which mediates signaling from all four mammalian Notch receptors, in the basal forebrain and ventral midbrain using the RBP-J-floxed mouse and a newly established Nestin-Cre mouse. We found that at early stage of neurogenesis (E11.5), the frequency of neurospheres increased significantly in the RBP-J-inactivated regions. The majority of the RBP-J deficient neurospheres were composed of INPs, suggesting the precocious differentiation of NSCs into INPs. Meanwhile, neuronal differentiation was reduced in the same regions at E11.5, inconsistent with the precocious differentiation phenotype in most Notch-related mutants. At late neurogenic stages (E17.5 and neonatal), as expected from precociously exhausted NSC pool, neurosphere frequency and NSCs decreased in the RBP-J-ablated regions, accompanied by a significant increase of both neurons and glial cells. These results indicated that the RBP-J-mediated signaling might inhibit the differentiation of NSCs into INPs and support the generation of certain early born neurons at early neurogenic stages.

Heterogeneous synthesis and electrochemical performance of LiMnPO4/C composites as cathode materials of lithium ion batteries.

In this study, a facile yet efficient interfacial hydrothermal process was successfully developed to fabricate LiMnPO4/C composites. In this strategy, the walls of carbon nanotubes were employed as heterogeneous nucleation interfaces and biomass of phytic acid (PA) as an eco-friendly phosphorus source. By comparing the experimental results, a reasonable nucleation-growth mechanism was proposed, suggesting the advantages of interfacial effects. Meanwhile, the as-synthesized LiMnPO4/C samples exhibited superior rate performances with discharge capacities reaching 161 mA h g-1 at C/20, 134 mA h g-1 at 1C, and 100 mA h g-1 at 5C. The composites also displayed excellent cycling stabilities by maintaining 95% of the initial capacity over 100 continuous cycles at 1C. Electrochemical impedance spectroscopy showed that the superior electrochemical performances were attributed to the low charge-transfer resistance and elevated diffusion coefficient of lithium ions. In sum, the proposed approach for the preparation of LiMnPO4/C composites looks promising for future production of composite electrode materials for high-performance lithium-ion batteries.

Excitatory and inhibitory effects of prolactin release activated by nerve stimulation in rat anterior pituitary.

BACKGROUND: A series of studies showed the presence of substantial amount of nerve fibers and their close relationship with the anterior pituitary gland cells. Our previous studies have suggested that aside from the classical theory of humoral regulation, the rat anterior pituitary has direct neural regulation on adrenocorticotropic hormone release. In rat anterior pituitary, typical synapses are found on every type of the hormone-secreting cells, many on lactotrophs. The present study was aimed at investigating the physiological significance of this synaptic relationship on prolactin release. METHODS: The anterior pituitary of rat was sliced and stimulated with electrical field in a self-designed perfusion chamber. The perfusate was continuously collected in aliquots and measured by radioimmunoassay for prolactin levels. After statistic analysis, differences of prolactin concentrations within and between groups were outlined. RESULTS: The results showed that stimulation at frequency of 2 Hz caused a quick enhancement of prolactin release, when stimulated at 10 Hz, prolactin release was found to be inhibited which came slower and lasted longer. The effect of nerve stimulation on prolactin release is diphasic and frequency dependent. CONCLUSIONS: The present in vitro study offers the first physiological evidence that stimulation of nerve fibers can affect prolactin release in rat anterior pituitary. Low frequency stimulation enhances prolactin release and high frequency mainly inhibits it.