Postsynaptic Targeting and Mobility of Membrane Surface-Localized hASIC1a / 神经科学通报·英文版

Acid-sensing ion channels (ASICs), the main H

Expression of acid-sensing ion channel 1a in the central nervous system of mice with panic-like behavior / 中华行为医学与脑科学杂志

Objective To explore the expression of acid-sensing ion channel 1a ( ASIC1a) in cen-tral nervous system of mice with panic like behavior. Methods 20 male C57BL/6 mice were randomly di-vided into two groups according to their weight( 10 mice in each group):the group experienced rat exposure test of panic-like behavior model ( RET group ) and the control group ( Ctr group ) . A panic-like behavior model was established by rat exposure stimuli. Ten minutes defensive and avoidance behaviors of mice were recorded with a horizontal video camera. The anxiety level of mice was evaluated by elevated plus maze ( EPM) test.Western blot was used to detect the ASIC 1a expression in different brain areas of prefrontal cor-tex,hippocampus and periaqueductal gray (PAG). Results Compared with Ctr group,mice in RET group spent significantly more time in freezing ((5.83±1.92)s) than that of Ctr group ((1.00±0.45)s) (P<0.01),had significantly higher frequency of risk assessment behavior (5.33±0.49) than that of Ctr group (0.60±0.40) (P<0.01),spent significantly less time to contact the wire mesh ((17.83±4.38)s) than that of Ctr group((50.00±6.90)s) (P<0.01),and significantly more time of staying in the protected area((431.00±33.13)s) than that of Ctr group((264.40±40.43)s) (P<0.01).At the same time,RET group showed sig-nificantly lower time percent ((8.28±1.12)％) than Ctr group ((16.81±2.13)％) in opened arm (P<0.05) and significantly higher time percent ((80.08±4.26)％) than Ctr group ((60.91±5.27)％) in the closed arm (P<0.05).Western blot suggested that the expression level of ASIC 1a in the prefrontal cortex (1.32± 0.05) and hippocampus (2.56±0.30) significantly increased than that of Ctr group((0.98±0.07),(1.56± 0.16)( P<0.05),while significantly decreased in the PAG (0.83± 0.02) than that of Ctr group(1.26±0.05) ( P<0.05) . Conclusion Rat exposure stimuli can induce panic-like behavior among mice,which increases the expression of ASIC 1a in the prefrontal cortex and hippocampus,but decreases the level of ASIC 1a in the PAG.

ASIC1a contributes to the symptom of pain in a rat model of chronic prostatitis / 亚洲男科学杂志(英文版)

This study aims to validate our hypothesis that acid-sensing ion channels (ASICs) may contribute to the symptom of pain in patients with chronic prostatitis (CP). We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASIC1a was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASIC1a on the Ca2+ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium ([Ca2+]i) intensity. The effect of ASIC1a on the p38/mitogen-activated protein kinase (MAPK) signaling pathway was also determined. ASIC1a was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASIC1a expression increased [Ca2+]i intensity in the dorsal horn neurons of rat spinal cord. ASIC1a also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASIC1a knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.

ASIC1a contributes to the symptom of pain in a rat model of chronic prostatitis / 亚洲男科学杂志(英文版)

This study aims to validate our hypothesis that acid-sensing ion channels (ASICs) may contribute to the symptom of pain in patients with chronic prostatitis (CP). We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASIC1a was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASIC1a on the Ca2+ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium ([Ca2+]i) intensity. The effect of ASIC1a on the p38/mitogen-activated protein kinase (MAPK) signaling pathway was also determined. ASIC1a was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASIC1a expression increased [Ca2+]i intensity in the dorsal horn neurons of rat spinal cord. ASIC1a also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASIC1a knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.

The fate of medications evaluated for ischemic stroke pharmacotherapy over the period 1995-2015

Stroke is a brain damage caused by a loss of blood supply to a portion of the brain, which requires prompt and effective treatment. The current pharmacotherapy for ischemic stroke primarily relies on thrombolysis using recombinant tissue plasminogen activators (rt-PAs) to breakdown blood clots. Neuroprotective agents that inhibit excitatory neurotransmitters are also used to treat ischemic stroke but have failed to translate into clinical benefits. This poses a major challenge in biomedical research to understand what causes the progressive brain cell death after stroke and how to develop an effective pharmacotherapy for stroke. This brief review analyzes the fate of about 430 potentially useful stroke medications over the period 1995-2015 and describes in detail those that successfully reached the market. Hopefully, the information from this analysis will shed light on how future stroke research can improve stroke drug discovery.