Synchronized oscillations at α and θ frequencies in the lateral geniculate nucleus

In relaxed wakefulness, the EEG exhibits robust rhythms in the alpha band (8-13 Hz), which decelerate to theta (approximately 2-7 Hz) frequencies during early sleep. In animal models, these rhythms occur coherently with synchronized activity in the thalamus. However, the mechanisms of this thalamic activity are unknown. Here we show that, in slices of the lateral geniculate nucleus maintained in vitro, activation of the metabotropic glutamate receptor (mGluR) mGluR1a induces synchronized oscillations at alpha and theta frequencies that share similarities with thalamic alpha and theta rhythms recorded in vivo. These in vitro oscillations are driven by an unusual form of burst firing that is present in a subset of thalamocortical neurons and are synchronized by gap junctions. We propose that mGluR1a-induced oscillations are a potential mechanism whereby the thalamus promotes EEG alpha and theta rhythms in the intact brain.

Human intervertebral disc aggrecan inhibits nerve growth in vitro

OBJECTIVE: To assess the effects of human intervertebral disc aggrecan on nerve growth and guidance, using in vitro techniques. METHODS: Aggrecan extracted from human lumbar intervertebral discs was incorporated into tissue culture substrata for the culture of the human neuronal cell line, SH-SY5Y, or explants of chick dorsal root ganglia. The effects on nerve growth of different concentrations of aggrecan extracted from the anulus fibrosus and nucleus pulposus, and of these aggrecan preparations following enzymic deglycosylation, were compared. RESULTS: Disc aggrecan inhibited the growth of neurites from SH-SY5Y cells and induced growth cone turning of chick sensory neurites in a concentration-dependent manner. Aggrecan isolated from the anulus fibrosus was more inhibitory than that isolated from the nucleus pulposus, but enzymic pretreatments to reduce the glycosylation of both types of disc aggrecan partially abrogated their inhibitory effects. CONCLUSION: Nerve growth into degenerate intervertebral discs has been linked with the development of low back pain, but little is known about factors affecting disc innervation. The finding that disc aggrecan inhibits nerve growth in vitro, and that this inhibitory activity depends on aggrecan glycosylation, has important implications for our understanding of mechanisms that may regulate disc innervation in health and disease.

Extracellular Nm23H1 stimulates neurite outgrowth from dorsal root ganglia neurons in vitro independently of nerve growth factor supplementation or its nucleoside diphosphate kinase activity

The nucleoside diphosphate (NDP) kinase, Nm23H1, is a highly expressed during neuronal development, whilst induced over-expression in neuronal cells results in increased neurite outgrowth. Extracellular Nm23H1 affects the survival, proliferation and differentiation of non-neuronal cells. Therefore, this study has examined whether extracellular Nm23H1 regulates nerve growth. We have immobilised recombinant Nm23H1 proteins to defined locations of culture plates, which were then seeded with explants of embryonic chick dorsal root ganglia (DRG) or dissociated adult rat DRG neurons. The substratum-bound extracellular Nm23H1 was stimulatory for neurite outgrowth from chick DRG explants in a concentration-dependent manner. On high concentrations of Nm23H1, chick DRG neurite outgrowth was extensive and effectively limited to the location of the Nm23H1, i.e. neuronal growth cones turned away from adjacent collagen-coated substrata. Nm23H1-coated substrata also significantly enhanced rat DRG neuronal cell adhesion and neurite outgrowth in comparison to collagen-coated substrata. These effects were independent of NGF supplementation. Recombinant Nm23H1 (H118F), which does not possess NDP kinase activity, exhibited the same activity as the wild-type protein. Hence, a novel neuro-stimulatory activity for extracellular Nm23H1 has been identified in vitro, which may function in developing neuronal systems. © 2010 Elsevier Inc.

O antagonismo do receptor de serotonina do tipo 7 da substância cinzenta periaquedutal dorsal reduz a ansiedade experimental basal, mas não aquela gerada pela retirada do etanol em ratos

Ethanol-dependent individuals who reduce or discontinue its use may present Alcohol Withdrawal Syndrome, which is characterized by unpleasant signs and symptoms, such as anxiety, that may trigger relapses. Ethanol, a psychotropic drug, is able to promote behavioral and neurophysiological changes, acting on different neurotransmitter systems, including the serotonergic, which has also been directly associated with aversive states, including anxiety. This study aimed to investigate the participation of type 7 serotonin receptor (5-HT7) of the dorsal periaqueductal gray (DPAG) on basal experimental anxiety and that caused by ethanol withdrawal. For this, 75-100 days old Wistar rats were subjected to two experiments. On the first one, animals underwent stereotactic surgery for implantation of guide cannulas used for administration of the drug directly into the DPAG. After seven days, the animals received doses of 2.5; 5 and 10 nmols of type 7 receptor antagonist SB269970 (SB) or vehicle intra-DPAG and, ten minutes after, they were exposed to elevated plus maze (EPM). In the following day, the animals were submitted to the same treatment and tested in the open field (OF). In the second experiment, animals received increasing concentrations (2%, 4%, 6%) of ethanol as the only source of liquid diet or water (control group), both with free access to chow. Seventy two hours and ninety six hours after the ethanol withdrawal, animals received SB (2.5 and 5.0 nmols) intraDPAG ten minutes before the test in the LCE and OF, respectively. In experiment 1, the dose of antagonist 10 nmols was able of reversing the anxiety generated by EPM. In the experiment 2, ineffective SB doses on the LCE (2.5 and 5.0 nmol) were not able to reverse the anxiety caused by the ethanol withdrawal in the EPM, although the dose of 2.5 nmols of SB has reversed its hipolocomotor effect in this test. This result suggests that the 5-HT7 receptor is involved in the modulation of the basal experimental anxiety in rats, but not in the anxiety caused by ethanol withdrawal in the DPAG.

Spitzer power-law active galactic nucleus candidates in the chandra deep field-north

We define a sample of 62 galaxies in the Chandra Deep Field-North whose Spitzer IRAC SEDs exhibit the characteristic power-law emission expected of luminous AGNs. We study the multiwavelength properties of this sample and compare the AGNs selected in this way to those selected via other Spitzer color-color criteria. Only 55% of the power-law galaxies are detected in the X-ray catalog at exposures of >0.5 Ms, although a search for faint emission results in the detection of 85% of the power-law galaxies at the ≥2.5 σ detection level. Most of the remaining galaxies are likely to host AGNs that are heavily obscured in the X-ray. Because the power-law selection requires the AGNs to be energetically dominant in the near- and mid-infrared, the power-law galaxies comprise a significant fraction of the Spitzer-detected AGN population at high luminosities and redshifts. The high 24 μm detection fraction also points to a luminous population. The power-law galaxies comprise a subset of color-selected AGN candidates. A comparison with various mid-infrared color selection criteria demonstrates that while the color-selected samples contain a larger fraction of the X-ray-luminous AGNs, there is evidence that these selection techniques also suffer from a higher degree of contamination by star-forming galaxies in the deepest exposures. Considering only those power-law galaxies detected in the X-ray catalog, we derive an obscured fraction of 68% (2 : 1). Including all of the power-law galaxies suggests an obscured fraction of <81% (4 : 1).

Monoaminergic Neuropathology in Alzheimer's disease

Acknowledgments This work was supported by The Croatian Science Foundation grant. no. IP-2014-09-9730 (“Tau protein hyperphosphorylation, aggregation, and trans-synaptic transfer in Alzheimer’s disease: cerebrospinal fluid analysis and assessment of protective neuroprotective compounds”) and European Cooperation in Science and Technology (COST) Action CM1103 (“Stucture-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain”). PRH is supported in part by NIH grant P50 AG005138.