In the present study we injected colchicine into the lateral ventricle of Sprague-Dawley rats to investigate the effects of colchicine on the number of different-type neurons in the basal forebrain and to search for n...In the present study we injected colchicine into the lateral ventricle of Sprague-Dawley rats to investigate the effects of colchicine on the number of different-type neurons in the basal forebrain and to search for neurons resistant to injury. After colchicine injection, the number of nestin^＋ cholinergic neurons was decreased at 1 day, but increased at 3 days and peaked at 14-28 days. The quantity of nestincholinergic neurons, parvalbumin-positive neurons and choline acetyl transferase-positive neurons decreased gradually. Our results indicate that nestin^＋ cholinergic neurons possess better tolerance to colchicine-induced neurotoxicity.展开更多
~[he cingulum, a long neural tract extending from the orbitof- rontal cortex to the medial temporal lobe, obtains cholinergic innervation from three cholinergic nuclei in the basal fore- brain （the nucleus basalis of...~[he cingulum, a long neural tract extending from the orbitof- rontal cortex to the medial temporal lobe, obtains cholinergic innervation from three cholinergic nuclei in the basal fore- brain （the nucleus basalis of Meynert [Ch 4], the medial septal nucleus [Ch 1 ], and the vertical nucleus of the diagonal band [Ch 2]）, and is the passage of the medial cholinergic pathway which supplies cholinergic innervation from the basal forebrain to the cerebral cortex （Folstein et al., 1975; Selden et al., 1998; Lucas-Meunier et al., 2003）. Therefore, it is important for cog- nition, especially memory function （Selden et al., 1998）.展开更多
BACKGROUND： Interferon-gamma （IFN-γ） can make neurons in basal forebrain and septal nuclei differentiate into cholinergic neurons by treating the cells in cerebral cortex of newborn rats, without the inhibition fr...BACKGROUND： Interferon-gamma （IFN-γ） can make neurons in basal forebrain and septal nuclei differentiate into cholinergic neurons by treating the cells in cerebral cortex of newborn rats, without the inhibition from IFN-γ antibody. The important effect of IFN-γ on the development and differentiation of neurons has been found by some scholars. OBJ EClIVE：To investigate whether IFN-γ has differentiational effect on cholinergic neurons in basal forebrain and septal nuclei, and make clear that the increased number of cholinergic neurons is resulted by cell differentiation or cell proliferation. DESIGN ： Controlled observation trial SETTING： Department of Cell Biology, Medical School, Beijing University MATERIALS： Sixty-eight female Wistar rats at embryonic 16 days, weighing 250 to 350 g, were enrolled in this study, and they were provided by the Experimental Animal Center, Medical School, Beijing University. IFN-γ was the product of Gibco Company. METHODS： This study was carried out in the Department of Cell Biology, Medical School, Beijing University and Daheng Image Company of Chinese Academy of Sciences during September 1995 to December 2002. The female Wistar rats at embryonic 16 days were sacrificed, and their fetuses were taken out. Primary culture of the isolated basal forebrain and septal nuclei was performed. The cultured nerve cells were assigned into 3 groups： control group （nothing added）, IFN-γ group（1×10^5 U/L interferon）, IFN-γ＋ IFN-γ antibody group （1 ×10^5 U/L IFN-γ ＋ IFN-γ antibody）. The specific marker enzyme （choline acetyl transferase） of cholinergic neuron was stained with immunohistochemical method. Choline acetyl transferase positive cells were counted, and ^14C-acetyl CoA was used as substrate to detect the activity of choline acetyl transferase, so as to reflect the differentiational effect of IFN-γ on cholinergic neuron in basal forebrain and septal nuclei. Flow cytometry was used to analyze cell circle and detect the proliferation of nerve cells. Nerve cells were marked with MAP2 and counted to evaluate the neuronal proliferation in basal forebrain and septal nuclei. MAIN OUTCOME MEASURES： Effect of interferon-γ on the number and activity of choline acetyl transferase-positive ceils in basal forebrain and septal nuclei as well as the effect on neuronal proliferation. RESULTS ： ① Nerve cells in the basal forebrain and septal nuclei of IFN-γ group grew well compared with control group.②The differentiation of cholinergic neurons： The number and activity of choline acetyl transferase positive cells in IFN-γ group were significantly higher than those in the control group [（49.30 ±4.92） /100 cells vs （7.50±1.58） /100 cells; （2 049.00±12.30） min^-1 vs （1 227.30±12.59） min^-1, p 〈 0.01], while there was no significant difference in the number and activity of choline acetyl transferase positive cells between IFN-γ ＋ IFN-γ antibody group and control group（P 〉 0.05）. ③The proliferation of cholinergic neurons： Cell percentage was 17.2% and 19.8% at S-stage, 6.2% and 6.1% at G2＋M stage in the control group and IFN-γ group respectively, without significant difference （P 〉 0.05）. CONCLUSION ： IFN-γ does not promote the neuronal proliferation in basal forebrain and septal nuclei, and the increased expression of cholinergic neurons is not resulted by the increase in the number of neurons, but its differentiation.展开更多
intraventricular injection of the immunotoxin,192-sap,that selectively de stroys neurons expressing the low affinity neurotrophin receptor,p75NGFr,efficiently and selectively destroys the cholinergic neurons of the ha...intraventricular injection of the immunotoxin,192-sap,that selectively de stroys neurons expressing the low affinity neurotrophin receptor,p75NGFr,efficiently and selectively destroys the cholinergic neurons of the hasal forebrain(CBF).In the present study,we sought to determine if there was a correlation between the degree of CBF neuron loss and alteration in passive avoidance behavior.Anesthetized,adult, male Sprague Dawley rats were stereotactically injected with 4μg of either 192-sap or OX7-sap,a control immunotoxin that recognizes the Thy 1 surface antigen and destroys cerebellar Purkinje neu rons. 6￣8 weeks later,immunotoxin and naive control rats were tested on step-through passive avoidance paradigm. After behavior-testing, all rats were sacrificed and brain sections processed for histochemical demonstration of AChE and immunohistochemical demonstration of p75NGFr.The numbers of neurons in specific regions of the CBF were counted from the P75NGFr,staining and the intensity of dorsolateral neocortical staining for AChE were assessed using image analysis. The magnitude of cell loss was similar(67 % ￣70%) for the entire CBF, the Nbm and septum/DBB. The seventy of passive avoidance impairment was significantly correlated to cell loss in the entire CBF (r= 0.748,23 df, P<0.001) and in the Nbm (r = 0.778, 23 df, P< 0.001) but not the septum/DBB (r=0. 419,23 df, P>0. 05).Behavioral impairment also correlated significantly to loss of conical AchE staining intensity ipsilateral to the intraventricular injections (r = 0.796,15df,P< 0.001).These fndings show that loss of Nbm, but not of septum/DBB,cholinergic neurons is proportional to impairment in passive avoidance behavior suggesting a role for Nbm-neocortex cholinergic innervation in this type of learning.(Supported by the Department of Veterans Affairs.)展开更多
基金the National Natural Science Foundation of China,No. 30700436
文摘In the present study we injected colchicine into the lateral ventricle of Sprague-Dawley rats to investigate the effects of colchicine on the number of different-type neurons in the basal forebrain and to search for neurons resistant to injury. After colchicine injection, the number of nestin^＋ cholinergic neurons was decreased at 1 day, but increased at 3 days and peaked at 14-28 days. The quantity of nestincholinergic neurons, parvalbumin-positive neurons and choline acetyl transferase-positive neurons decreased gradually. Our results indicate that nestin^＋ cholinergic neurons possess better tolerance to colchicine-induced neurotoxicity.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education,No.2015R1D1A4A01020385
文摘~[he cingulum, a long neural tract extending from the orbitof- rontal cortex to the medial temporal lobe, obtains cholinergic innervation from three cholinergic nuclei in the basal fore- brain （the nucleus basalis of Meynert [Ch 4], the medial septal nucleus [Ch 1 ], and the vertical nucleus of the diagonal band [Ch 2]）, and is the passage of the medial cholinergic pathway which supplies cholinergic innervation from the basal forebrain to the cerebral cortex （Folstein et al., 1975; Selden et al., 1998; Lucas-Meunier et al., 2003）. Therefore, it is important for cog- nition, especially memory function （Selden et al., 1998）.
基金the National Nat-ural Science Foundation of Chi-na, No.39570249
文摘BACKGROUND： Interferon-gamma （IFN-γ） can make neurons in basal forebrain and septal nuclei differentiate into cholinergic neurons by treating the cells in cerebral cortex of newborn rats, without the inhibition from IFN-γ antibody. The important effect of IFN-γ on the development and differentiation of neurons has been found by some scholars. OBJ EClIVE：To investigate whether IFN-γ has differentiational effect on cholinergic neurons in basal forebrain and septal nuclei, and make clear that the increased number of cholinergic neurons is resulted by cell differentiation or cell proliferation. DESIGN ： Controlled observation trial SETTING： Department of Cell Biology, Medical School, Beijing University MATERIALS： Sixty-eight female Wistar rats at embryonic 16 days, weighing 250 to 350 g, were enrolled in this study, and they were provided by the Experimental Animal Center, Medical School, Beijing University. IFN-γ was the product of Gibco Company. METHODS： This study was carried out in the Department of Cell Biology, Medical School, Beijing University and Daheng Image Company of Chinese Academy of Sciences during September 1995 to December 2002. The female Wistar rats at embryonic 16 days were sacrificed, and their fetuses were taken out. Primary culture of the isolated basal forebrain and septal nuclei was performed. The cultured nerve cells were assigned into 3 groups： control group （nothing added）, IFN-γ group（1×10^5 U/L interferon）, IFN-γ＋ IFN-γ antibody group （1 ×10^5 U/L IFN-γ ＋ IFN-γ antibody）. The specific marker enzyme （choline acetyl transferase） of cholinergic neuron was stained with immunohistochemical method. Choline acetyl transferase positive cells were counted, and ^14C-acetyl CoA was used as substrate to detect the activity of choline acetyl transferase, so as to reflect the differentiational effect of IFN-γ on cholinergic neuron in basal forebrain and septal nuclei. Flow cytometry was used to analyze cell circle and detect the proliferation of nerve cells. Nerve cells were marked with MAP2 and counted to evaluate the neuronal proliferation in basal forebrain and septal nuclei. MAIN OUTCOME MEASURES： Effect of interferon-γ on the number and activity of choline acetyl transferase-positive ceils in basal forebrain and septal nuclei as well as the effect on neuronal proliferation. RESULTS ： ① Nerve cells in the basal forebrain and septal nuclei of IFN-γ group grew well compared with control group.②The differentiation of cholinergic neurons： The number and activity of choline acetyl transferase positive cells in IFN-γ group were significantly higher than those in the control group [（49.30 ±4.92） /100 cells vs （7.50±1.58） /100 cells; （2 049.00±12.30） min^-1 vs （1 227.30±12.59） min^-1, p 〈 0.01], while there was no significant difference in the number and activity of choline acetyl transferase positive cells between IFN-γ ＋ IFN-γ antibody group and control group（P 〉 0.05）. ③The proliferation of cholinergic neurons： Cell percentage was 17.2% and 19.8% at S-stage, 6.2% and 6.1% at G2＋M stage in the control group and IFN-γ group respectively, without significant difference （P 〉 0.05）. CONCLUSION ： IFN-γ does not promote the neuronal proliferation in basal forebrain and septal nuclei, and the increased expression of cholinergic neurons is not resulted by the increase in the number of neurons, but its differentiation.
文摘intraventricular injection of the immunotoxin,192-sap,that selectively de stroys neurons expressing the low affinity neurotrophin receptor,p75NGFr,efficiently and selectively destroys the cholinergic neurons of the hasal forebrain(CBF).In the present study,we sought to determine if there was a correlation between the degree of CBF neuron loss and alteration in passive avoidance behavior.Anesthetized,adult, male Sprague Dawley rats were stereotactically injected with 4μg of either 192-sap or OX7-sap,a control immunotoxin that recognizes the Thy 1 surface antigen and destroys cerebellar Purkinje neu rons. 6￣8 weeks later,immunotoxin and naive control rats were tested on step-through passive avoidance paradigm. After behavior-testing, all rats were sacrificed and brain sections processed for histochemical demonstration of AChE and immunohistochemical demonstration of p75NGFr.The numbers of neurons in specific regions of the CBF were counted from the P75NGFr,staining and the intensity of dorsolateral neocortical staining for AChE were assessed using image analysis. The magnitude of cell loss was similar(67 % ￣70%) for the entire CBF, the Nbm and septum/DBB. The seventy of passive avoidance impairment was significantly correlated to cell loss in the entire CBF (r= 0.748,23 df, P<0.001) and in the Nbm (r = 0.778, 23 df, P< 0.001) but not the septum/DBB (r=0. 419,23 df, P>0. 05).Behavioral impairment also correlated significantly to loss of conical AchE staining intensity ipsilateral to the intraventricular injections (r = 0.796,15df,P< 0.001).These fndings show that loss of Nbm, but not of septum/DBB,cholinergic neurons is proportional to impairment in passive avoidance behavior suggesting a role for Nbm-neocortex cholinergic innervation in this type of learning.(Supported by the Department of Veterans Affairs.)
