scholarly journals Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zhilu Zou ◽  
Yin Chen ◽  
Qinqin Shen ◽  
Xiaoyan Guo ◽  
Yuxuan Zhang ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Learned Helplessness ◽  
Low Dose ◽  
Critical Role ◽  
Repeated Administration ◽  
Camp Response Element Binding ◽  
Antidepressant Effect ◽  
Long Term Depression

Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH) protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF) and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling.

TGF-β1-Induced Long-Term Changes in Neuronal Excitability in Aplysia Sensory Neurons Depend on MAPK

2006 ◽  
Vol 95 (5) ◽  
pp. 3286-3290 ◽  
Author(s):  
Jeannie Chin ◽  
Rong-Yu Liu ◽  
Leonard J. Cleary ◽  
Arnold Eskin ◽  
John H. Byrne
Keyword(s):  
Sensory Neuron ◽  
Transforming Growth Factor Beta ◽  
Neuronal Excitability ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Camp Response Element Binding ◽  
Long Term Changes ◽  
Tgf Β1

Transforming growth factor beta-1 (TGF-β1) plays important roles in the early development of the nervous system and has been implicated in neuronal plasticity in adult organisms. It induces long-term increases in sensory neuron excitability in Aplysia as well as a long-term enhancement of synaptic efficacy at sensorimotor synapses. In addition, TGF-β1 acutely regulates synapsin phosphorylation and reduces synaptic depression induced by low-frequency stimuli. Because of the critical role of MAPK in other forms of long-term plasticity in Aplysia, we examined the role of MAPK in TGF-β1-induced long-term changes in neuronal excitability. Prolonged (6 h) exposure to TGF-β1 induced long-term increases in excitability. We confirmed this finding and now report that exposure to TGF-β1 was sufficient to activate MAPK and increase nuclear levels of active MAPK. Moreover, TGF-β1 enhanced phosphorylation of the Aplysia transcriptional activator cAMP response element binding protein (CREB)1, a homologue to vertebrate CREB. Both the TGF-β1-induced long-term changes in neuronal excitability and the phosphorylation of CREB1 were blocked in the presence of an inhibitor of the MAPK cascade, confirming a role for MAPK in long-term modulation of sensory neuron function.

scholarly journals A Critical Role of the Nitric Oxide/cGMP Pathway in Corticostriatal Long-Term Depression

1999 ◽  
Vol 19 (7) ◽  
pp. 2489-2499 ◽  
Author(s):  
Paolo Calabresi ◽  
Paolo Gubellini ◽  
Diego Centonze ◽  
Giuseppe Sancesario ◽  
Maria Morello ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Critical Role ◽  
Long Term Depression ◽  
Cgmp Pathway

Persistent Pulmonary Hypertension of the Newborn: Role of Nitric Oxide

1995 ◽  
Vol 10 (6) ◽  
pp. 270-282
Author(s):  
Stella Kourembanas
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Structural Changes ◽  
Critical Role ◽  
Persistent Pulmonary Hypertension ◽  
Cell Contractility ◽  
Vasoactive Mediators ◽  
Nitric Oxide Therapy

Persistent pulmonary hypertension of the newborn (PPHN) is a common cause of respiratory failure in the full-term neonate. Molecular and cellular studies in vascular biology have revealed that endothelial-derived mediators play a critical role in the pathogenesis and treatment of PPHN. Endothelial-derived vasoconstrictors, like endothelin, may increase smooth muscle cell contractility and growth, leading to the physiologic and structural changes observed in the pulmonary arterioles of infants with this disease. On the other hand, decreased production of the endothelial-derived relaxing factor, nitric oxide, may exacerbate pulmonary vasoreactivity and lead to more severe pulmonary hypertension. Exogenous (inhaled) nitric oxide therapy reduces pulmonary vascular resistance and improves oxygenation. The safety and efficacy of this therapy in reducing the need for extracorporeal membrane oxygenation and decreasing long-term morbidity is being tested in several trials nationally and abroad. Understanding the basic mechanisms that regulate the gene expression and production of these vasoactive mediators will lead to improved preventive and therapeutic strategies for PPHN.

Short‐ and long‐term responsiveness to low dose growth hormone (GH) in adult GH deficiency: Role of GH receptor polymorphism

2019 ◽  
Vol 31 (4) ◽  
pp. e12692 ◽  
Author(s):  
Antonio Bianchi ◽  
Antonella Giampietro ◽  
Linda Tartaglione ◽  
Sabrina Chiloiro ◽  
Raffaella Gentilella ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Low Dose ◽  
Gh Deficiency ◽  
Gh Receptor ◽  
Adult Gh Deficiency ◽  
Short And Long Term ◽  
Receptor Polymorphism

Suppression of the glutamate receptor delta 2 subunit produces a specific impairment in cerebellar long-term depression

1996 ◽  
Vol 76 (5) ◽  
pp. 3578-3583 ◽  
Author(s):  
A. Jeromin ◽  
R. L. Huganir ◽  
D. J. Linden
Keyword(s):  
Glutamate Receptor ◽  
Antisense Oligonucleotide ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Calcium Influx ◽  
Long Term Depression ◽  
Metabotropic Glutamate ◽  
Flow Through

1. The role of the glutamate receptor subunit delta 2 in the induction of cerebellar long-term depression (LTD) was investigated by application of antisense oligonucleotides. The delta 2 subunit is selectively localized to Purkinje cells (PCs), with the highest levels being in the PC dendritic spines, where parallel fibers are received and where cerebellar LTD is expressed. 2. Immunocytochemical analysis of calbindin-positive PCs revealed that both the dendritic and somatic expression of delta 2 was reduced in antisense-but not in sense-treated cultures. An antisense oligonucleotide directed against the related subunit delta 1 did not affect the expression of delta 2 in PCs. 3. Cerebellar LTD may be reliably induced in a preparation of cultured embryonic cerebellar neurons from the mouse when parallel and climbing fiber stimulation are replaced by brief glutamate pulses and strong, direct depolarization of the PC, respectively. Application of an antisense oligonucleotide directed against delta 2 completely blocked the induction of LTD produced by glutamate/ depolarization conjunctive stimulation. A delta 2 sense oligonucleotide or an antisense oligonucleotide directed against the related delta 1 subunit had no effect. 4. The effect of the delta 2 antisense oligonucleotide was not related to attenuation of calcium influx via voltage-gated channels or calcium mobilization via metabotropic glutamate receptors, as assessed with fura-2 microfluorimetry. Current flow through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor-associated ion channels also appeared unaltered. All three of these processes have previously been shown to be required for cerebellar LTD induction. The observation that delta 2 is involved in a metabotropic-glutamate-receptor-independent signaling pathway that is required for LTD induction supports the view that delta 2 participates in the formation of a novel postsynaptic receptor complex.

Sign in / Sign up

Export Citation Format

Share Document