Niping Wang

Melatonin-selenium nanoparticles inhibit oxidative stress and protect against hepatic injury induced by Bacillus Calmette-Guérin/lipopolysaccharide in mice.

Abstract:  Melatonin‐selenium nanoparticles (MT‐Se), a novel complex, were synthesized by preparing selenium nanoparticles in melatonin medium. The present investigation was designed to determine the protective effects of MT‐Se against Bacillus Calmette–Guérin (BCG)/lipopolysaccharide (LPS)‐induced hepatic injury in mice. In BCG/LPS‐induced hepatic injury model, MT‐Se administered (i.g.) at doses of 5, 10, or 20 mg/kg to BCG/LPS‐treated mice for 10 days, significantly reduced the increase in plasma aminotransferase, reduced the severe extent of hepatic cell damage and the immigration of inflammatory cells. The MT‐Se particles also attenuated the increase in the content of thiobarbituric acid‐reactive substances and enhanced the decrease in reduced activities of superoxide dismutase and glutathione peroxidase (GPx). However, treatment with MT‐Se suppressed the increase in nitric oxide levels both in plasma and liver tissue. Furthermore, supplementation with MT‐Se at the dose of 10 mg/kg (composed of 9.9 mg/kg melatonin and 0.1 mg/kg selenium) had great capability to protect against hepatocellular damage than a similar dose of melatonin (10 mg/kg) or selenium (0.1 mg/kg) alone. This effect may relate to its higher antioxidant efficacy in decreasing lipid peroxidation and increasing GPx activity. These results suggest that the mode of MT‐Se hepatic protective action is, at least in part, related to its antioxidant properties.

Peripheral Muscle Targets and Central Projections of the Mesencephalic Trigeminal Nucleus in Macaque Monkeys

The mesencephalic trigeminal nucleus (MesV) contains the somata of primary afferent neurons that innervate muscle spindles in masticatory muscles and mechanoreceptors in the periodontal ligaments. There are conflicting reports about additional peripheral targets of MesV, such as the extraocular muscles, as well as about its central targets. In addition, only limited primate data are available. Consequently, we examined MesV projections in macaque monkeys. The retrograde tracer wheat germ agglutinin‐conjugated horseradish peroxidase (WGA‐HRP) was injected into masticatory or extraocular muscles to define the peripheral targets of the primate MesV. Numerous labeled neurons were found in ipsilateral MesV after masticatory muscle injections. The scattered distribution of labeled cells, and their presence among clusters of unlabeled cells, suggests the muscle representations overlap. Just a few MesV neurons were labeled after extraocular muscle injections. This correlates with the small number of muscle spindles present in macaque extraocular muscles, suggesting MesV cells supplying extraocular muscle spindles may contribute a minor component to oculomotor proprioception. To examine the central connections of MesV, biotinylated dextran amine (BDA) was injected into the spinal trigeminal nucleus (Vs). The presence of retrogradely labeled MesV cells indicated a projection to Vs from MesV. These injections also anterogradely labeled terminals that lay in close association with MesV cells, suggesting an ascending projection from Vs to MesV. Finally, a small number of MesV neurons were labeled after WGA‐HRP injections into the upper cervical spinal cord. This pattern of central connections indicates MesV and Vs information is combined to guide mastication. Anat Rec, 291:974–987, 2008.

Anatomical Evidence that the Superior Colliculus Controls Saccades through Central Mesencephalic Reticular Formation Gating of Omnipause Neuron Activity

Omnipause neurons (OPNs) within the nucleus raphe interpositus (RIP) help gate the transition between fixation and saccadic eye movements by monosynaptically suppressing activity in premotor burst neurons during fixation, and releasing them during saccades. Premotor neuron activity is initiated by excitatory input from the superior colliculus (SC), but how the tectums saccade-related activity turns off OPNs is not known. Since the central mesencephalic reticular formation (cMRF) is a major SC target, we explored whether this nucleus has the appropriate connections to support tectal gating of OPN activity. In dual-tracer experiments undertaken in macaque monkeys (Macaca fascicularis), cMRF neurons labeled retrogradely from injections into RIP had numerous anterogradely labeled terminals closely associated with them following SC injections. This suggested the presence of an SC–cMRF–RIP pathway. Furthermore, anterograde tracers injected into the cMRF of other macaques labeled axonal terminals in RIP, confirming this cMRF projection. To determine whether the cMRF projections gate OPN activity, postembedding electron microscopic immunochemistry was performed on anterogradely labeled cMRF terminals with antibody to GABA or glycine. Of the terminals analyzed, 51.4% were GABA positive, 35.5% were GABA negative, and most contacted glycinergic cells. In summary, a trans-cMRF pathway connecting the SC to the RIP is present. This pathway contains inhibitory elements that could help gate omnipause activity and allow other tectal drives to induce the bursts of firing in premotor neurons that are necessary for saccades. The non-GABAergic cMRF terminals may derive from fixation units in the cMRF.

The macaque midbrain reticular formation sends side-specific feedback to the superior colliculus

The central mesencephalic reticular formation (cMRF) likely plays a role in gaze control, as cMRF neurons receive tectal input and provide a bilateral projection back to the superior colliculus (SC). We examined the important question of whether this feedback is excitatory or inhibitory. Biotinylated dextran amine (BDA) was injected into the cMRF of M.fascicularis monkeys to anterogradely label reticulotectal terminals and retrogradely label tectoreticular neurons. BDA labeled profiles in the ipsi- and contralateral intermediate gray layer (SGI) were examined electron microscopically. Postembedding GABA immunochemistry was used to identify putative inhibitory profiles. Nearly all (94.7%) of the ipsilateral BDA labeled terminals were GABA positive, but profiles postsynaptic to these labeled terminals were exclusively GABA negative. In addition, BDA labeled terminals were observed to contact BDA labeled dendrites, indicating the presence of a monosynaptic feedback loop connecting the cMRF and ipsilateral SC. In contrast, within the contralateral SGI, half of the BDA labeled terminals were GABA positive, while more than a third were GABA negative. All the postsynaptic profiles were GABA negative. These results indicate the cMRF provides inhibitory feedback to the ipsilateral side of the SC, but it has more complex effects on the contralateral side. The ipsilateral projection may help tune the “winner-take-all” mechanism that produces a unified saccade signal, while the contralateral projections may contribute to the coordination of activity between the two colliculi.

Melatonin-selenium nanoparticles protects liver against immunological injury induced by bacillus Calmette-Guérin and lipopolysaccharide

AbstractAim:Melatonin-selenium nanoparticle (MT-Se), a novel complex, was synthesized by preparing selenium nanoparticles in a melatonin medium. The present investigation was designed to determine the protective effects of MT-Se against immunological liver injury in mice induced by bacillus Calmette-Guérin (BCG)/ lipopolysaccharide (LPS).Methods:The model of immunological liver injury in mice was prepared. The levels of alanine aminotransferase, aspartate aminotransferase, nitric oxide (NO) in serum, malondialdehyde content, superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) activities in a liver homogenate were assayed by spectrophotometry. The content of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) were determined by ELISA. The splenocyte proliferation was assayed by 3-[4,5-dimethylthiazol-2-yl] -2,5-diphenyltetra-zolium bromide (MTT) dye reduction. Meanwhile, a hepatic pathological examination was observed.Results:In the BCG/LPS-induced hepatic injury model, MT-Se administered at doses of 5, 10, or 20 mg/kg to the BCG/LPS-treated mice for 10 d significantly reduced the increase in serum aminotransferase, reduced the severe extent of hepatic cell damage and the immigration of inflammatory cells. It also attenuated the increase in the content of thiobarbituric acid-reactive substances and enhanced the decrease in activities of SOD and GSH-px. In contrast, the treatment with MT-Se suppressed the increase in NO level in both the serum and liver tissue. Furthermore, MT-Se significantly lowered an increase in TNF-α and IL-1α levels in the liver and inhibited the production of TNF-α and IL-1α by peritoneal macrophages. A downregulation effect of MT-Se on splenocyte proliferation was also observed.Conclusion:MT-Se showed a hepatic protective action on immunological liver injury in mice.

Binge ethanol exposure increases the Krüppel-like factor 11-monoamine oxidase (MAO) pathway in rats: Examining the use of MAO inhibitors to prevent ethanol-induced brain injury.

Binge drinking induces several neurotoxic consequences including oxidative stress and neurodegeneration. Because of these effects, drugs which prevent ethanol-induced damage to the brain may be clinically beneficial. In this study, we investigated the ethanol-mediated KLF11-MAO cell death cascade in the frontal cortex of Sprague-Dawley rats exposed to a modified Majchowicz 4-day binge ethanol model and control rats. Moreover, MAO inhibitors (MAOIs) were investigated for neuroprotective activity against binge ethanol. Binge ethanol-treated rats demonstrated a significant increase in KLF11, both MAO isoforms, protein oxidation and caspase-3, as well as a reduction in BDNF expression in the frontal cortex compared to control rats. MAOIs prevented these binge ethanol-induced changes, suggesting a neuroprotective benefit. Neither binge ethanol nor MAOI treatment significantly affected protein expression levels of the oxidative stress enzymes, SOD2 or catalase. Furthermore, ethanol-induced antinociception was enhanced following exposure to the 4-day ethanol binge. These results demonstrate that the KLF11-MAO pathway is activated by binge ethanol exposure and MAOIs are neuroprotective by preventing the binge ethanol-induced changes associated with this cell death cascade. This study supports KLF11-MAO as a mechanism of ethanol-induced neurotoxicity and cell death that could be targeted with MAOI drug therapy to alleviate alcohol-related brain injury. Further examination of MAOIs to reduce alcohol use disorder-related brain injury could provide pivotal insight to future pharmacotherapeutic opportunities.

Reticular Formation Connections Underlying Horizontal Gaze: The Central Mesencephalic Reticular Formation (cMRF) as a Conduit for the Collicular Saccade Signal

The central mesencephalic reticular formation (cMRF) occupies much of the core of the midbrain tegmentum. Physiological studies indicate that it is involved in controlling gaze changes, particularly horizontal saccades. Anatomically, it receives input from the ipsilateral superior colliculus (SC) and it has downstream projections to the brainstem, including the horizontal gaze center located in the paramedian pontine reticular formation (PPRF). Consequently, it has been hypothesized that the cMRF plays a role in the spatiotemporal transformation needed to convert spatially coded collicular saccade signals into the temporally coded signals utilized by the premotor neurons of the horizontal gaze center. In this study, we used neuroanatomical tracers to examine the patterns of connectivity of the cMRF in macaque monkeys in order to determine whether the circuit organization supports this hypothesis. Since stimulation of the cMRF produces contraversive horizontal saccades and stimulation of the horizontal gaze center produces ipsiversive saccades, this would require an excitatory cMRF projection to the contralateral PPRF. Injections of anterograde tracers into the cMRF did produce labeled terminals within the PPRF. However, the terminations were denser ipsilaterally. Since the PPRF located contralateral to the movement direction is generally considered to be silent during a horizontal saccade, we then tested the hypothesis that this ipsilateral reticuloreticular pathway might be inhibitory. The ultrastructure of ipsilateral terminals was heterogeneous, with some displaying more extensive postsynaptic densities than others. Postembedding immunohistochemistry for gamma-aminobutyric acid (GABA) indicated that only a portion (35%) of these cMRF terminals are GABAergic. Dual tracer experiments were undertaken to determine whether the SC provides input to cMRF reticuloreticular neurons projecting to the ipsilateral pons. Retrogradely labeled reticuloreticular neurons were predominantly distributed in the ipsilateral cMRF. Anterogradely labeled tectal terminals were observed in close association with a portion of these retrogradely labeled reticuloreticular neurons. Taken together, these results suggest that the SC does have connections with reticuloreticular neurons in the cMRF. However, the predominantly excitatory nature of the ipsilateral reticuloreticular projection argues against the hypothesis that this cMRF pathway is solely responsible for producing a spatiotemporal transformation of the collicular saccade signal.