Developing a mouse model of acute encephalopathy using low-dose lipopolysaccharide injection and hyperthermia treatment.

IMPACT STATEMENT: Acute encephalopathy (AE), mainly reported in East Asia, is classified into four categories based on clinical and neuropathological findings. Among them, AE caused by cytokine storm is known as the severest clinical entity that causes cerebral edema with poor prognosis. Because suitable and convenient model animal of AE had not been developed, the treatment of patients with AE is not established. In the present study, we established a simple and convenient protocol to mimic AE due to cytokine storm. Our model animal should be useful to elucidate the pathogenesis of AE.

Identification of NeuN immunopositive cells in the adult mouse subventricular zone.

In the adult rodent subventricular zone (SVZ), there are neural stem cells (NSCs) and the specialized neurogenic niche is critical to maintain their stemness. To date, many cellular and noncellular factors that compose the neurogenic niche and markers to identify subpopulations of Type A cells have been confirmed. In particular, neurotransmitters regulate adult neurogenesis and mature neurons in the SVZ have been only partially analyzed. Moreover, Type A cells, descendants of NSCs, are highly heterogeneous and more molecular markers are still needed to identify them. In the present study, we systematically classified NeuN, commonly used as a marker of mature and immature post-mitotic neurons, immunopositive (+) cells within the adult mouse SVZ. These SVZ-NeuN+ cells (SVZ-Ns) were mainly classified into two types. One was mature SVZ-Ns (M-SVZ-Ns). Neurochemical properties of M-SVZ-Ns were similar to those of striatal neurons, but their birth date and morphology were different. M-SVZ-Ns were generated during embryonic and early postnatal stages with bipolar peaks and extended their processes along the wall of the lateral ventricle. The second type was small SVZ-Ns (S-SVZ-Ns) with features of Type A cells. They expressed not only markers of Type A cells, but also proliferated and migrated from the SVZ to the olfactory bulb. Furthermore, S-SVZ-Ns could be classified into two types by their spatial locations and glutamic acid decarboxylase 67 expression. Our data indicate that M-SVZ-Ns are a new component of the neurogenic niche and S-SVZ-Ns are newly identified subpopulations of Type A cells.

c-jun is differentially expressed in embryonic and adult neural precursor cells.

c-jun, a major component of AP-1 transcription factor, has a wide variety of functions. In the embryonic brain, c-jun mRNA is abundantly expressed in germinal layers around the ventricles. Although the subventricular zone (SVZ) of the adult brain is a derivative of embryonic germinal layers and contains neural precursor cells (NPCs), the c-jun expression pattern is not clear. To study the function of c-jun in adult neurogenesis, we analyzed c-jun expression in the adult SVZ by immunohistochemistry and compared it with that of the embryonic brain. We found that almost all proliferating embryonic NPCs expressed c-jun, but the number of c-jun immunopositive cells among proliferating adult NPCs was about half. In addition, c-jun was hardly expressed in post-mitotic migrating neurons in the embryonic brain, but the majority of c-jun immunopositive cells were tangentially migrating neuroblasts heading toward the olfactory bulb in the adult brain. In addition, status epilepticus is known to enhance the transient proliferation of adult NPCs, but the c-jun expression pattern was not significantly affected. These expression patterns suggest that c-jun has a pivotal role in the proliferation of embryonic NPCs, but it has also other roles in adult neurogenesis.

Utilization of photoinduced charge-separated state of donor-acceptor-linked molecules for regulation of cell membrane potential and ion transport.

The control of ion transport across cell membranes by light is an attractive strategy that allows targeted, fast control of precisely defined events in the biological membrane. Here we report a novel general strategy for the control of membrane potential and ion transport by using charge-separation molecules and light. Delivery of charge-separation molecules to the plasma membrane of PC12 cells by a membranous nanocarrier and subsequent light irradiation led to depolarization of the membrane potential as well as inhibition of the potassium ion flow across the membrane. Photoregulation of the cell membrane potential and ion transport by using charge-separation molecules is highly promising for control of cell functions.