NAc-DBS corrects depression-like behaviors in CUMS mouse model via disinhibition of DA neurons in the VTA.

Major depressive disorder (MDD) is characterized by diverse debilitating symptoms that include loss of motivation and anhedonia. If multiple medications, psychotherapy, and electroconvulsive therapy fail in some patients with MDD, their condition is then termed treatment-resistant depression (TRD). MDD can be associated with abnormalities in the reward-system-dopaminergic mesolimbic pathway, in which the nucleus accumbens (NAc) and ventral tegmental area (VTA) play major roles.

Smoothened is a therapeutic target for reducing glutamate toxicity in ischemic stroke.

Extracellular glutamate contributes to brain damage in ischemia. Under physiological conditions, glutamate transporters are responsible for regulating its intracellular/extracellular concentrations in the brain. However, how the extracellular glutamate is regulated in ischemia remains unclear.

Epitranscriptome of the ventral tegmental area in a deep brain-stimulated chronic unpredictable mild stress mouse model.

Deep brain stimulation (DBS) applied to the nucleus accumbens (NAc) alleviates the depressive symptoms of major depressive disorders. We investigated the mechanism of this effect by assessing gene expression and RNA methylation changes in the ventral tegmental area (VTA) following NAc-DBS in a chronic unpredictable mild stress (CUMS) mouse model of depression. Gene expression and -methyladenosine (mA) levels in the VTA were measured in mice subjected to CUMS and then DBS, and transcriptome-wide mA changes were profiled using immunoprecipitated methylated RNAs with microarrays, prior to gene ontology analysis.

TRPC Channels in Health and Disease.

This chapter offers a brief introduction of the functions of TRPC channels in non-neuronal systems. We focus on three major organs of which the research on TRPC channels have been most focused on: kidney, heart, and lung. The chapter highlights on cellular functions and signaling pathways mediated by TRPC channels.

Sonic hedgehog is a regulator of extracellular glutamate levels and epilepsy.

Sonic hedgehog (Shh), both as a mitogen and as a morphogen, plays an important role in cell proliferation and differentiation during early development. Here, we show that Shh inhibits glutamate transporter activities in neurons, rapidly enhances extracellular glutamate levels, and affects the development of epilepsy. Shh is quickly released in response to epileptic, but not physiological, stimuli.

Activin/BMP2 chimeric ligands direct adipose-derived stem cells to chondrogenic differentiation.

Human adipose derived stem cells (hASCs) can be easily isolated and their plasticity has been well characterized. Several TGF-β superfamily ligands can direct hASCs towards chondrocytes. However, these ligands are difficult to purify and expensive.

Compound screening platform using human induced pluripotent stem cells to identify small molecules that promote chondrogenesis.

Articular cartilage, which is mainly composed of collagen II, enables smooth skeletal movement. Degeneration of collagen II can be caused by various events, such as injury, but degeneration especially increases over the course of normal aging. Unfortunately, the body does not fully repair itself from this type of degeneration, resulting in impaired movement.

Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin.

Critical role of TRPC6 channels in VEGF-mediated angiogenesis.

Intracellular Ca(2+) signaling plays critical roles in VEGF-mediated angiogenesis. Transient receptor potential canonical (TRPC) channel 6, a Ca(2+)-permeable non-selective cation channel, can be activated by VEGF. Here, we report that TRPC6 is important for VEGF-mediated angiogenesis.

ZNF23 induces apoptosis in human ovarian cancer cells.

We recently reported that the level of ZNF23, a KRAB-containing zinc finger protein, is reduced in human cancers and it inhibits cell growth by inducing cell cycle arrest. Here we showed that ZNF23 also induces apoptosis in ovarian cancer cells. The protein level of ZNF23 in ovarian cancers was greatly down-regulated compared with that in the normal ovaries.

The Kv4.2 mediates excitatory activity-dependent regulation of neuronal excitability in rat cortical neurons.

Neuronal excitability can cooperate with synaptic transmission to control the information storage. This regulation of neuronal plasticity can be affected by alterations in neuronal inputs and accomplished by modulation of voltage-dependent ion channels. In this study, we report that enhanced excitatory input negatively regulated neuronal excitability.

Characterization of ZNF23, a KRAB-containing protein that is downregulated in human cancers and inhibits cell cycle progression.

The Krupple-associated box-containing zinc-finger proteins (KRAB-ZFPs) make up one of the largest family of transcription factors. Several members of the KRAB-ZFPs modulate cell growth, survival and are implicated in malignant disorders. However, most members are not well characterized and their functions are largely unknown.