Biomedical subjects

Yuan Fan

Publications and source records attributed to Yuan Fan.

5 recordsLinked to original sources

PubMed2007

Morphological heterogeneity of CA1 pyramidal neurons in response to ischemia.

We have found, based on the electrophysiological properties, two subtypes of CA1 pyramidal neurons in the CA1 region of the normal hippocampus, late postsynaptic potential (L-PSP) neurons and non-L-PSP neurons. In addition, our previous study has shown that the electrophysiological properties of these two subtypes of pyramidal neurons were differentially modified after ischemia. In the present study, we hypothesized that ischemia might also induce different morphological alterations in these two subtypes of neuron. To test the hypothesis, we compared the changes in the dendritic arborization and soma volume of these two subtypes of neurons in rats subjected to transient global ischemia. We found a significant decrease in the basal dendritic length of L-PSP neurons at 12 hr after reperfusion, resulting mainly from a significant decrease in the dendrite terminal length. The apical dendritic length of L-PSP neurons markedly increased at 24 hr after ischemia, resulting mainly from an increase in the number of branching arbors in the middle part of the apical dendritic trees. The soma size of L-PSP neurons was significantly reduced at 12 hr, but they became slightly larger at 24 hr and 48 hr after reperfusion. In contrast to L-PSP neurons, non-L-PSP neurons showed slight modifications in the dendritic arborization but had persistent swelling of their soma after ischemia. These results indicate that pathological changes in these two subtypes of neurons are different after ischemia.

Animals↗

PubMed2005

Activity-dependent decrease of excitability in rat hippocampal neurons through increases in I(h).

Hippocampal long-term potentiation (LTP) induced by theta-burst pairing of Schaffer collateral inputs and postsynaptic firing is associated with localized increases in synaptic strength and dendritic excitability. Using the same protocol, we now demonstrate a decrease in cellular excitability that was blocked by the h-channel blocker ZD7288. This decrease was also induced by postsynaptic theta-burst firing alone, yet it was blocked by NMDA receptor antagonists, postsynaptic Ca2+ chelation, low concentrations of tetrodotoxin, omega-conotoxin MVIIC, calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitors and a protein synthesis inhibitor. Increasing network activity with high extracellular K+ caused a similar reduction of cellular excitability and an increase in h-channel HCN1 protein. We propose that backpropagating action potentials open glutamate-bound NMDA receptors, resulting in an increase in I(h) and a decrease in overall excitability. The occurrence of such a reduction in cellular excitability in parallel with synaptic potentiation would be a negative feedback mechanism to normalize neuronal output firing and thus promote network stability.

2-Amino-5-phosphonovalerate↗

PubMed2004

In vivo demonstration of a late depolarizing postsynaptic potential in CA1 pyramidal neurons.

Previous studies have shown that GABA can have a depolarizing and excitatory action through GABA(A) receptors in mature CNS neurons in vitro. However, it remains unknown whether this occurs under physiological conditions. In this study, using intracellular recording and staining in vivo technique, we show a late depolarizing postsynaptic potential (L-PSP) in CA1 pyramidal neurons of adult Wistar rats under halothane anesthesia. This L-PSP was elicited in approximately 70% of the recorded neurons on stimulation of the Schaffer collaterals or the contralateral commissural path. The size of L-PSP was linearly correlated to the decay time constant but not the rising slope of the initial excitatory PSP (EPSP). Intravenous administration of the N-methyl-D-aspartate (NMDA) receptor blocker MK-801 and the GABA(A) receptor blocker picrotoxin significantly reduced the size of the L-PSP. The spine density and apical dendritic branching length of the neurons that displayed L-PSPs was significantly greater than those that do not. These results indicate that NMDA receptor and GABA(A) receptor-mediated depolarizing postsynaptic potentials can be revealed in CA1 pyramidal neurons of adult rats in vivo, supporting the physiological relevance of GABA(A)-mediated depolarization in normal neuronal information processing. The difference in electrophysiological properties and morphological features between neurons that display the L-PSP and the other neurons suggest that they might represent two different subtypes of CA1 pyramidal neurons.

Animals↗

PubMed2004

The PGL family proteins associate with germ granules and function redundantly in Caenorhabditis elegans germline development.

PGL-1 is a constitutive protein component of C. elegans germ granules, also known as P granules. Maternally supplied PGL-1 is essential for germline development but only at elevated temperature, raising the possibility that redundant factors provide sufficient function at lower temperatures. We have identified two PGL-1-related proteins, PGL-2 and PGL-3, by sequence analysis of the C. elegans genome and by a yeast two-hybrid screen for proteins that interact with PGL-1. PGL-3 is associated with P granules at all stages of development, while PGL-2 is associated with P granules only during postembryonic development. All three PGL proteins interact with each other in vitro. Furthermore, PGL-1 and PGL-3 are co-immunoprecipitated from embryo extracts, indicating that they are indeed in the same protein complex in vivo. Nevertheless, each PGL protein localizes to P granules independently of the other two. pgl-2 or pgl-3 single-mutant worms do not show obvious defects in germline development. However, pgl-1; pgl-3 (but not pgl-2; pgl-1) double-mutant hermaphrodites and males show significantly enhanced sterility at all temperatures, compared to pgl-1 alone. Mutant hermaphrodites show defects in germline proliferation and in production of healthy gametes and viable embryos. Our findings demonstrate that both PGL-2 and PGL-3 are components of P granules, both interact with PGL-1, and at least PGL-3 functions redundantly with PGL-1 to ensure fertility in both sexes of C. elegans.

Amino Acid Sequence↗

PubMed2004

[The expression of apoptosis-associated proteins Bcl-2, Bax in oral leukoplakia and lichen planus].

PURPOSE: The purpose of this study was to explore the pathogenesis and carcinogenesis of oral leukoplakia (LK) and oral lichen planus (OLP) by examining the expression of apoptosis-associated proteins Bcl-2 Bax in LK and OLP. METHODS: The expression of Bcl-2 and Bax were measured in 10 cases of normal oral mucosa,18 cases of OLP, 23 cases of LK and 22 cases of oral squamous cell carcinoma (SCC) by immunohistochemical assays. RESULTS: In the epithelial cell layer of LK and OLP, the positive Bcl-2 expression was similar to oral normal mucosa,but in the part of the lymphocytic infiltration of OLP, overexpression of Bcl-2 was observed. In the SCC, the Bcl-2 expression was significantly higher than that in normal oral mucosa(P<0.05). In the tissue of simple hyperplasia, mild dysplasia, moderate dysplasia, poorly differentiated SCC and erosive OLP, the expression of Bax was significantly higher than that in normal oral mucosa (P<0.05). CONCLUSIONS: Bax was closely related to the early event of LK carcinogenesis. Bcl-2 may not play a role in LK carcinogenesis. Bcl-2 and Bax play an important role in pathogenesis of OLP. We postulate that the Bcl-2 inhibits the apoptosis of lymphocytes that strengthen the cell-mediated immune process and the overexpression of Bax was related to the apoptosis of epithelial cells in OLP.

Apoptosis↗