Role of neuropsin in parvalbumin immunoreactivity changes in hippocampal basket terminals of mice reared in various environments.

In vitro approaches have suggested that neuropsin (or kallikrein 8/KLK8), which controls gamma-aminobutyric acid (GABA) neurotransmission through neuregulin-1 (NRG-1) and its receptor (ErbB4), is involved in neural plasticity (Tamura et al., 2012, 2013). In the present study, we examined whether parvalbumin (PV)-positive neuronal networks, the majority of which are ErbB4-positive GABAergic interneurons, are controlled by neuropsin in tranquil and stimulated voluntarily behaving mice. Parvalbumin-immunoreactive fibers surrounding hippocampal pyramidal and granular neurons in mice reared in their home cage were decreased in neuropsin-deficient mice, suggesting that neuropsin controls PV immunoreactivity. One- or two-week exposures of wild mice to novel environments, in which they could behave freely and run voluntarily in a wheel resulted in a marked upregulation of both neuropsin mRNA and protein in the hippocampus. To elucidate the functional relevance of the increase in neuropsin during exposure to a rich environment, the intensities of PV-immunoreactive fibers were compared between neuropsin-deficient and wild-type (WT) mice under environmental stimuli. When mice were transferred into novel cages (large cages with toys), the intensity of PV-immunoreactive fibers increased in WT mice and neuropsin-deficient mice. Therefore, behavioral stimuli control a neuropsin-independent form of PV immunoreactivity. However, the neuropsin-dependent part of the change in PV-immunoreactive fibers may occur in the stimulated hippocampus because increased levels of neuropsin continued during these enriched conditions.

[Simultaneous relapse of Basedow's disease in a patient with adult-onset Still's disease].

This report describes a 50-year-old woman with coexisting Basedow's disease and adult-onset Still's disease (AOSD) that relapsed simultaneously. She was diagnosed with Basedow's disease in 1999, and treatment with antithyroid agents was started. However, the treatment was soon stopped because of severe side effects. A partial thyroidectomy was performed and the thyroid function stayed well-controlled after the surgery. In August 2007, she was admitted to our hospital with fever, a sore throat, skin rashes, arthritis and leukocytosis, and was diagnosed with AOSD. At the same time, her laboratory data revealed decreased serum TSH and elevated serum free T4, suggesting a relapse of Basedow's disease. After initiation of steroid pulse therapy accompanied by oral prednisolone, both diseases improved significantly. Prednisolone was gradually reduced, and the disease activity remained in remission. Immediately after prednisolone reached 3 mg/day in November 2009, both diseases relapsed. Prednisolone was increased to 30 mg/day, and the diseases became well-controlled again. In this case, Basedow's disease was aggravated when AOSD was in the active stage. Literature searches revealed five previously reported cases with coexisting Basedow's disease and AOSD. In four of the six cases, including our case, both diseases were activated simultaneously. AOSD in the active stage is known to cause hypercytokinemia and immunological derangement. Our case indicated that the pathogenesis of AOSD might lead to relapse of coexisting Basedow's disease.

Characteristics of the control of standing posture during pregnancy.

During pregnancy, the physical and mental states greatly change. We investigated the influences of pregnancy and anxiety on postural control in pregnant women (P) standing upright in the late trimester. An analysis of posturograms revealed that the area of body sway and length of antero-posterior body sway were greater in P than those in non-pregnant controls (NP). No difference was found in the medio-lateral body sway between P and NP. Fast Fourier transform analysis of body sway showed that the percentile power of the 1.0-10.0Hz band in the medio-lateral axis was smaller in P than in NP irrespective of whether the eyes were open or closed. P were divided into a high (HA) and low (LA) anxiety group on the basis of state anxiety scored by Spielberger's State- and Trait-Anxiety Inventory. A positive correlation was identified between state anxiety and the area of body sway in HA standing with eyes open. This correlation was diminished when the eyes were closed. Body sway of over 1Hz is generally stabilized by somatosensory input, therefore, the results show that body sway in the medio-lateral axis is stabilized in P by increasing the sensitivity to somatosensory cues. High anxiety during pregnancy destabilizes the standing posture when the eyes are open. The correlation between anxiety and body sway revealed by our previous studies in college students was also confirmed in P, suggesting that humans with high anxiety abstract visual cues differently from those with low anxiety.

Area-specific resonance of excitatory networks in neocortex: control by outward currents.

During disinhibition or low [Mg++](o) buffer, 7-14 Hz ( approximately 10 Hz) oscillations are generated by excitatory networks of interconnected pyramidal cells in motor (agranular) cortex but are absent in barrel (granular) cortex. Here we studied if the inability of barrel cortex to produce approximately 10 Hz oscillations during these conditions is because barrel cortex networks lack the necessary cellular mechanisms or, alternatively, because those mechanisms are inhibited by outward currents. The results show that blockers of slowly inactivating voltage-dependent K+ currents unmask approximately 10 Hz oscillations in barrel cortex, and this occurs in unison with the unmasking of intrinsic inward Ca++ currents that are kept suppressed by the outward currents. Moreover, the approximately 10 Hz oscillations unmasked in barrel cortex occur independently in upper and lower layers indicating that the approximately 10 Hz oscillation mechanisms are kept suppressed in multiple networks. The results reveal that the propensity of distinct excitatory networks of neocortex to generate epileptiform oscillatory activities is controlled by outward currents.

Resonance (approximately 10 Hz) of excitatory networks in motor cortex: effects of voltage-dependent ion channel blockers.

The motor cortex generates synchronous network oscillations at frequencies between 7 and 14 Hz during disinhibition or low [Mg2+]o buffers, but the underlying mechanisms are poorly understood. These oscillations, termed here approximately 10 Hz oscillations, are generated by a purely excitatory network of interconnected pyramidal cells because they are robust in the absence of GABAergic transmission. It is likely that specific voltage-dependent currents expressed in those cells contribute to the generation of approximately 10 Hz oscillations. We tested the effects of different drugs known to suppress certain voltage-dependent currents. The results revealed that drugs that suppress the low-threshold calcium current and the hyperpolarization-activated cation current are not critically involved in the generation of approximately 10 Hz oscillations. Interestingly, drugs known to suppress the persistent sodium current abolished approximately 10 Hz oscillations. Furthermore, blockers of K+ channels had significant effects on the oscillations. In particular, blockers of the M-current abolished the oscillations. Also, blockers of both non-inactivating and slowly inactivating voltage-dependent K+ currents abolished approximately 10 Hz oscillations. The results indicate that specific voltage-dependent non-inactivating K+ currents, such as the M-current, and persistent sodium currents are critically involved in generating approximately 10 Hz oscillations of excitatory motor cortex networks.