ELECTROACUPUNCTURE AT BAIHUI ACUPOINT (GV20) REVERSES BEHAVIOR DEFICIT AND LONG-TERM POTENTIATION THROUGH N-METHYL-D-ASPARTATE AND TRANSIENT RECEPTOR POTENTIAL VANILLOID SUBTYPE 1 RECEPTORS IN MIDDLE CEREBRAL ARTERY OCCLUSION RATS

2010 ◽  
Vol 09 (03) ◽  
pp. 269-282 ◽  
Author(s):  
YI-WEN LIN ◽  
CHING-LIANG HSIEH
2021 ◽  
Vol 15 ◽  
Author(s):  
Jon Egaña-Huguet ◽  
Miquel Saumell-Esnaola ◽  
Svein Achicallende ◽  
Edgar Soria-Gomez ◽  
Itziar Bonilla-Del Río ◽  
...  

The transient receptor potential vanilloid 1 (TRPV1) participates in synaptic functions in the brain. In the dentate gyrus, post-synaptic TRPV1 in the granule cell (GC) dendritic spines mediates a type of long-term depression (LTD) of the excitatory medial perforant path (MPP) synapses independent of pre-synaptic cannabinoid CB1 receptors. As CB1 receptors also mediate LTD at these synapses, both CB1 and TRPV1 might be influencing the activity of each other acting from opposite synaptic sites. We tested this hypothesis in the MPP–GC synapses of mice lacking TRPV1 (TRPV1-/-). Unlike wild-type (WT) mice, low-frequency stimulation (10 min at 10 Hz) of TRPV1-/- MPP fibers elicited a form of long-term potentiation (LTP) that was dependent on (1) CB1 receptors, (2) the endocannabinoid 2-arachidonoylglycerol (2-AG), (3) rearrangement of actin filaments, and (4) nitric oxide signaling. These functional changes were associated with an increase in the maximum binding efficacy of guanosine-5′-O-(3-[35S]thiotriphosphate) ([35S]GTPγS) stimulated by the CB1 receptor agonist CP 55,940, and a significant decrease in receptor basal activation in the TRPV1-/- hippocampus. Finally, TRPV1-/- hippocampal synaptosomes showed an augmented level of the guanine nucleotide-binding (G) Gαi1, Gαi2, and Gαi3 protein alpha subunits. Altogether, the lack of TRPV1 modifies CB1 receptor signaling in the dentate gyrus and causes the shift from CB1 receptor-mediated LTD to LTP at the MPP–GC synapses.


2012 ◽  
Vol 32 (6) ◽  
pp. 978-982 ◽  
Author(s):  
Mirko Muzzi ◽  
Roberta Felici ◽  
Leonardo Cavone ◽  
Elisabetta Gerace ◽  
Alberto Minassi ◽  
...  

Although treatment of stroke patients with mild hypothermia is a promising therapeutic approach, chemicals inducing prompt and safe reduction of body temperature are an unmet need. We measured the effects of the transient receptor potential vanilloid-1 (TRPV1) agonist rinvanil on thermoregulation and ischemic brain injury in mice. Intraperitoneal or intracerebroventricular injection of rinvanil induces mild hypothermia that is prevented by the receptor antagonist capsazepine. Both intraischemic and postischemic treatments provide permanent neuroprotection in animals subjected to transient middle cerebral artery occlusion (MCAo), an effect lost in mice artificially kept normothermic. Data indicate that TRPV1 receptor agonists are promising candidates for hypothermic treatment of stroke.


2010 ◽  
Vol 299 (1) ◽  
pp. H106-H113 ◽  
Author(s):  
Hirotsugu Tsuchimochi ◽  
Jennifer L. McCord ◽  
Shawn G. Hayes ◽  
Satoshi Koba ◽  
Marc P. Kaufman

In decerebrated rats, we determined the pressor and cardioaccelerator reflex responses to static contraction of hindlimb muscles whose femoral arteries were either occluded 72 h before contraction, occluded 3 min before contraction, or freely perfused. We found that the pressor reflex arising from the limb whose femoral artery was occluded for 72 h before contraction (32 ± 5 mmHg, n = 16) was significantly higher than the pressor reflex arising from the contralateral freely perfused limb (15 ± 3 mmHg, n = 16, P < 0.001) or than that arising from the contralateral limb whose femoral artery was occluded for only 3 min (17 ± 4 mmHg, n = 16, P < 0.001). Moreover, the pressor reflex arising from the limb whose femoral artery was occluded for 3 min before the start of contraction was not significantly different than that arising from the contralateral freely perfused limb ( n = 16, P = 0.819). The pressor component of the reflex arising from the limb whose femoral artery was occluded for 72 h was not changed by transient receptor potential vanilloid (TRPV) 1 receptor blockade with iodo-resiniferatoxin ( n = 15, P = 0.272), although the cardioaccelerator component was significantly reduced ( P = 0.005). In addition, the pressor response evoked by capsaicin injection in the femoral artery of the 72-h occluded limb was more than double that evoked from the freely perfused limb ( P = 0.026). We conclude that chronic (i.e., 72 h) but not acute (3 min), femoral arterial occlusion augments pressor reflex arising from contraction of hindlimb muscles and that TRPV1 receptors play little role in this augmentation.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Krishnamurthy Nakuluri ◽  
Rajkishor Nishad ◽  
Dhanunjay Mukhi ◽  
Sireesh Kumar ◽  
Venkata P. Nakka ◽  
...  

AbstractPodocytes are specialized cells of the glomerulus and key component of the glomerular filtration apparatus (GFA). GFA regulates the permselectivity and ultrafiltration of blood. The mechanism by which the integrity of the GFA is compromised and manifest in proteinuria during ischemic stroke remains enigmatic. We investigated the mechanism of ischemic hypoxia-induced proteinuria in a middle cerebral artery occlusion (MCAO) model. Ischemic hypoxia resulted in the accumulation of HIF1α in the podocytes that resulted in the increased expression of ZEB2 (Zinc finger E-box-binding homeobox 2). ZEB2, in turn, induced TRPC6 (transient receptor potential cation channel, subfamily C, member 6), which has increased selectivity for calcium. Elevated expression of TRPC6 elicited increased calcium influx and aberrant activation of focal adhesion kinase (FAK) in podocytes. FAK activation resulted in the stress fibers reorganization and podocyte foot process effacement. Our study suggests overactive HIF1α/ZEB2 axis during ischemic-hypoxia raises intracellular calcium levels via TRPC6 and consequently altered podocyte structure and function thus contributes to proteinuria.


PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Feng Gao ◽  
Yi Liang ◽  
Xiang Wang ◽  
Zongshi Lu ◽  
Li Li ◽  
...  

High-salt diet-induced cardiac hypertrophy and fibrosis are associated with increased reactive oxygen species production. Transient receptor potential vanilloid type 1 (TRPV1), a specific receptor for capsaicin, exerts a protective role in cardiac remodeling that resulted from myocardial infarction, and peroxisome proliferation-activated receptorsδ(PPAR-δ) play an important role in metabolic myocardium remodeling. However, it remains unknown whether activation of TRPV1 could alleviate cardiac hypertrophy and fibrosis and the effect of cross-talk between TRPV1 and PPAR-δon suppressing high-salt diet-generated oxidative stress. In this study, high-salt diet-induced cardiac hypertrophy and fibrosis are characterized by significant enhancement of HW/BW%, LVEDD, and LVESD, decreased FS and EF, and increased collagen deposition. These alterations were associated with downregulation of PPAR-δ, UCP2 expression, upregulation of iNOS production, and increased oxidative/nitrotyrosine stress. These adverse effects of long-term high-salt diet were attenuated by chronic treatment with capsaicin. However, this effect of capsaicin was absent in TRPV1−/−mice on a high-salt diet. Our finding suggests that chronic dietary capsaicin consumption attenuates long-term high-salt diet-induced cardiac hypertrophy and fibrosis. This benefit effect is likely to be caused by TRPV1 mediated upregulation of PPAR-δexpression.


2019 ◽  
Author(s):  
Krishnamurthy Nakuluri ◽  
Rajkishor Nishad ◽  
Dhanunjay Mukhi ◽  
Sireesh Kumar ◽  
Venkata P Nakka ◽  
...  

AbstractGlomerular filtration apparatus (GFA) regulates the glomerular permselectivity and ultrafiltration of urine. Podocytes are specialized cells and a key component of the GFA. The mechanism by which the integrity of the GFA is compromised and manifest in proteinuria during ischemic stroke remains enigmatic. Hypoxia is a determining factor in the pathophysiology of ischemia. We investigated the mechanism of ischemic-hypoxia induced proteinuria in a middle cerebral artery occlusion (MCAO) model. Ischemic hypoxia resulted in the accumulation of HIF1α in the glomerular podocytes that resulted in the increased expression of ZEB2. ZEB2, in turn, induced TRPC6 (transient receptor potential cation channel, subfamily C, member 6), which has increased selectivity for calcium. Elevated expression of TRPC6 elicited increased calcium influx and aberrant activation of focal adhesion kinase (FAK) in podocytes. FAK activation resulted in the stress fibers reorganization and podocyte foot process effacement. Our study suggests overactive HIF1α/ZEB2 axis during ischemic-hypoxia induces intracellular calcium levels via TRPC6 and consequently altered podocyte integrity and permselectivity.


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