Objective:To study the derivatives of 1,2,4-triazino[5,6-b]indole-3-thione for antidepressant activity in olfactory bulbectomized(OBX)rats.Out of various derivatives tested for acute tail suspension test,the two deriv...Objective:To study the derivatives of 1,2,4-triazino[5,6-b]indole-3-thione for antidepressant activity in olfactory bulbectomized(OBX)rats.Out of various derivatives tested for acute tail suspension test,the two derivatives showiug prominent action were.selected for bilateral olfactory bulbeetomy rsodel of ehronic depression in rats.Methods:The sub aeute effects of 14-day oral pretreatment of two derivatives labeled as 3a(70 mg/kg)and 3r(70 mg/kg),imipramine(20 mg/kg),fluoxetiue(30 mg/kg)and moclobemide(15 mg/kg)were evaluated on bilateral bulbectomy induced rise in body weight,hyperphagia,hyperactivity,and on sexual dysfunction.The serum sodium concentration,body temperature,and heart rate were also recorded.Results:The derivatives3a and 3r showed reversal of drop in body weight,reversed OBX indueed hyperactivity,normalized body temperature,heart rate,and serum sodium concentration.In elevated maze test,moclobemide,3a,3r treatment significantly redueed time spent in open arm as compared to OBX rats.3a and 3r also irsproved sexual behavior parameters.Conclusions:The present study shows promising antidepressant action and provides a proof of concept for the chronic treatrsent of 3a,3r to treat depression.展开更多
The olfactory system is one of a few areas in the nervous system which is capable of regeneration throughout the life.Olfactory sensory neurons reside in the nasal cavity are continuously replenished with new neurons ...The olfactory system is one of a few areas in the nervous system which is capable of regeneration throughout the life.Olfactory sensory neurons reside in the nasal cavity are continuously replenished with new neurons arising from stem cells.Some factors such as aging,neurodegenerative diseases,head trauma,brain tumor extraction and infection cause olfactory dysfunction which significantly influences physical wellbeing,quality of life,mental health,nutritional status,memory processes,identifying danger and is associated with increased mortality.Therefore,finding a treatment to improve olfactory dysfunction is needed.Recent research efforts in the field have shown some very promising new approaches to treat olfactory dysfunction.This review explores the current studies that have addressed therapeutic approaches to improve olfactory neuron regeneration based on cell transplantation therapy,modulation of physiological olfactory dysfunction and drug treatments.展开更多
Alzheimer’s disease (AD) is the common cause of dementia which shows the neuro-pathologies like an accumulation of amyloid-</span><i style="font-family:""><span style="font-family:V...Alzheimer’s disease (AD) is the common cause of dementia which shows the neuro-pathologies like an accumulation of amyloid-</span><i style="font-family:""><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;"> (A</span><i style="font-family:""><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">) and degeneration of cholinergic neuron. Olfactory bulbectomized (OBX) mice show some of AD features, so they have been used to research as AD model. Mesenchymal stem cells (MSCs) can differentiate into many kinds of cells, including neuronal cells. In this study, we intranasally administrated the conditioned medium derived from cultured umbilical cord (UC) MSCs. The intranasal administration of the MSCs medium restored the cognitive impairment observed in OBX mice. In addition, the decreased number of choline acetyltransferase-positive cells in the medial septum was restored by the conditioned medium administration. In conclusion, MSCs-derived conditioned medium may have protective effects of cholinergic neurons in the medial septum, thereby rescuing the cognitive impairment of OBX.展开更多
Objective Recently,there has been growing interest in the interaction between depressive disorders and pain.The purpose of this study was to examine whether depression would lead to a decreased sensitivity to noxious ...Objective Recently,there has been growing interest in the interaction between depressive disorders and pain.The purpose of this study was to examine whether depression would lead to a decreased sensitivity to noxious stimuli in rats with spontaneous pain.Methods The olfactory bulbectomized rats were used as a model of depression.The depression-like behaviors were assessed by open field test and changes in body weight.Formalin solution was injected into the rat hindpaw to produce ongoing pain.Noxious thermal stimuli were applied onto the hindpaw contralateral to formalin injection,and the withdrawal thresholds were measured.Results In non-depressive rats,the formalin-treated paw developed hypoalgesia to noxious stimuli while the contralateral paw was not affected.The depressive rats,however,showed a significantly lower sensitivity to noxious thermal stimulus,represented as higher withdrawal thresholds of the contralateral paw,when compared to the non-depressive rats.Conclusion These results demonstrate that depression can alleviate the stimulus-evoked pain even in the context of formalin inflammatory pain,consistent with the previous clinical observations that patients suffering from both depression and persistent pain have decreased sensitivities to noxious experimental stimuli.展开更多
Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherap...Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro–Gly–Pro(PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles(PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala(BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized(OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell–nanoparticle delivery system for depression therapy.展开更多
文摘Objective:To study the derivatives of 1,2,4-triazino[5,6-b]indole-3-thione for antidepressant activity in olfactory bulbectomized(OBX)rats.Out of various derivatives tested for acute tail suspension test,the two derivatives showiug prominent action were.selected for bilateral olfactory bulbeetomy rsodel of ehronic depression in rats.Methods:The sub aeute effects of 14-day oral pretreatment of two derivatives labeled as 3a(70 mg/kg)and 3r(70 mg/kg),imipramine(20 mg/kg),fluoxetiue(30 mg/kg)and moclobemide(15 mg/kg)were evaluated on bilateral bulbectomy induced rise in body weight,hyperphagia,hyperactivity,and on sexual dysfunction.The serum sodium concentration,body temperature,and heart rate were also recorded.Results:The derivatives3a and 3r showed reversal of drop in body weight,reversed OBX indueed hyperactivity,normalized body temperature,heart rate,and serum sodium concentration.In elevated maze test,moclobemide,3a,3r treatment significantly redueed time spent in open arm as compared to OBX rats.3a and 3r also irsproved sexual behavior parameters.Conclusions:The present study shows promising antidepressant action and provides a proof of concept for the chronic treatrsent of 3a,3r to treat depression.
基金supported by a grant from the Perry Cross Spinal Research Foundation to FC,JASTby Queensland University of Technology to FC
文摘The olfactory system is one of a few areas in the nervous system which is capable of regeneration throughout the life.Olfactory sensory neurons reside in the nasal cavity are continuously replenished with new neurons arising from stem cells.Some factors such as aging,neurodegenerative diseases,head trauma,brain tumor extraction and infection cause olfactory dysfunction which significantly influences physical wellbeing,quality of life,mental health,nutritional status,memory processes,identifying danger and is associated with increased mortality.Therefore,finding a treatment to improve olfactory dysfunction is needed.Recent research efforts in the field have shown some very promising new approaches to treat olfactory dysfunction.This review explores the current studies that have addressed therapeutic approaches to improve olfactory neuron regeneration based on cell transplantation therapy,modulation of physiological olfactory dysfunction and drug treatments.
文摘Alzheimer’s disease (AD) is the common cause of dementia which shows the neuro-pathologies like an accumulation of amyloid-</span><i style="font-family:""><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;"> (A</span><i style="font-family:""><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">) and degeneration of cholinergic neuron. Olfactory bulbectomized (OBX) mice show some of AD features, so they have been used to research as AD model. Mesenchymal stem cells (MSCs) can differentiate into many kinds of cells, including neuronal cells. In this study, we intranasally administrated the conditioned medium derived from cultured umbilical cord (UC) MSCs. The intranasal administration of the MSCs medium restored the cognitive impairment observed in OBX mice. In addition, the decreased number of choline acetyltransferase-positive cells in the medial septum was restored by the conditioned medium administration. In conclusion, MSCs-derived conditioned medium may have protective effects of cholinergic neurons in the medial septum, thereby rescuing the cognitive impairment of OBX.
基金supported by the grants from National Natural Science Foundation of China(No.30700223,30770688,30970959)Beijing Natural Science Foundation(No.5082008)+2 种基金the 100 Talented Plan of the Chinese Academy of Sciencesthe National Hi-Tech Research and Development Program of China(No.2008AA022604)NIH Fogarty International Center(R03-TW 008038)
文摘Objective Recently,there has been growing interest in the interaction between depressive disorders and pain.The purpose of this study was to examine whether depression would lead to a decreased sensitivity to noxious stimuli in rats with spontaneous pain.Methods The olfactory bulbectomized rats were used as a model of depression.The depression-like behaviors were assessed by open field test and changes in body weight.Formalin solution was injected into the rat hindpaw to produce ongoing pain.Noxious thermal stimuli were applied onto the hindpaw contralateral to formalin injection,and the withdrawal thresholds were measured.Results In non-depressive rats,the formalin-treated paw developed hypoalgesia to noxious stimuli while the contralateral paw was not affected.The depressive rats,however,showed a significantly lower sensitivity to noxious thermal stimulus,represented as higher withdrawal thresholds of the contralateral paw,when compared to the non-depressive rats.Conclusion These results demonstrate that depression can alleviate the stimulus-evoked pain even in the context of formalin inflammatory pain,consistent with the previous clinical observations that patients suffering from both depression and persistent pain have decreased sensitivities to noxious experimental stimuli.
基金financial support from the National Natural Science Foundation of China (81673372, 81690263, 81361140344 and 81773911)the National Basic Research Program of China (2013CB 932502)+2 种基金the Opening Project of Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education (Sichuan University, Chengdu, China)the Development Project of Shanghai Peak Disciplines–Integrated Medicine (No. 20150407)the Open Project Program of Key Lab of Smart Drug Delivery (Hehai University, Shanghai, China), Ministry of Education, China
文摘Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro–Gly–Pro(PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles(PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala(BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized(OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell–nanoparticle delivery system for depression therapy.
