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The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro.

Lu L, Dong H, Liu G, Yuan B, Li Y, Liu H - Biomol Ther (Seoul) (2014)

Bottom Line: Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage.DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 μmol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours.These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Shandong University Affiliated Shandong Provincial Hospital, Jinan 250021.

ABSTRACT
Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 μmol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (>25 μm), whereas ddC mainly affected small diameter DRG neurons (≤25 μm). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

No MeSH data available.


Related in: MedlinePlus

Neurite outgrowth in different experimental conditions. Panel A: control; Panel B: gp120 (500 pmol/L); Panel C: ddC (50 μmol/L); Panel D: gp120 (500 pmol/L)+ddC (50 μmol/L); Panel E: gp120 (500 pmol/L)+IGF-1 (20 nmol/L); Panel F: ddC (50 μmol/L)+IGF-1 (20 nmol/L); Panel G: gp120 (500 pmol/L)+ddC (50 μmol/L)+IGF-1 (20 nmol/L). A2-G2 are enlargements of small neurons in A1-G1 with thin arrows. A3-G3 are enlargements of large neurons in A1-G1 with thick arrows. Scale bar=50 μm.
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f1-bt-22-532: Neurite outgrowth in different experimental conditions. Panel A: control; Panel B: gp120 (500 pmol/L); Panel C: ddC (50 μmol/L); Panel D: gp120 (500 pmol/L)+ddC (50 μmol/L); Panel E: gp120 (500 pmol/L)+IGF-1 (20 nmol/L); Panel F: ddC (50 μmol/L)+IGF-1 (20 nmol/L); Panel G: gp120 (500 pmol/L)+ddC (50 μmol/L)+IGF-1 (20 nmol/L). A2-G2 are enlargements of small neurons in A1-G1 with thin arrows. A3-G3 are enlargements of large neurons in A1-G1 with thick arrows. Scale bar=50 μm.

Mentions: To determine the total neurite length of each small DRG neuron, DRG neuronal cultures at 72 hours after treatment with different agents were processed for fluorescent labeling of MAP2. The total neurite length of each small DRG neuron (the diameter of neuronal cell body ≤25 μm) was measured. The mean total neurite length of small neurons in control group, gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L)+ddC (50 μmol/L), gp120 (500 pmol/L)+IGF-1 (20 nmol/L), ddC (50 μmol/L)+IGF-1 (20 nmol/L), and gp120 (500 pmol/L)+ddC (50 μmol/L)+IGF-1 (20 nmol/L) treated cultures was 296.3 μm ± 19.5 μm, 205.5 μm ± 20.7 μm, 178.6 μm ± 15.9 μm, 167.6 μm ± 15.9 μm, 246.2 μm ± 19.1 μm, 222.7 μm ± 13.3 μm, and 205.6 μm ± 14.52 μm, respectively. Exposure of gp120 and/or ddC induced neurite retraction of small DRG neurons (gp120, F=0.014, p=0.000; ddC, F=0.420, p=0.000; gp120+ddC, F=0.301, p=0.000). Interestingly, ddC exposure alone caused more severe neurite retraction of small DRG neurons compared with that in gp120-treated cultures (F=0.172, p=0.047). The combination of gp120 and ddC did not induce any further decreases in total neurite length of small DRG neurons compared with that in ddC-treated cultures suggesting a ceiling effect. Exogenous IGF-1 application could partially reverse the neurite retraction of small DRG neurons (gp120, F=0.009, p=0.012; ddC, F=0.079, p=0.001; gp120+ddC, F=0.047, p=0.004) (Fig. 1, 2).


The Protective Effects of IGF-1 on Different Subpopulations of DRG Neurons with Neurotoxicity Induced by gp120 and Dideoxycytidine In Vitro.

Lu L, Dong H, Liu G, Yuan B, Li Y, Liu H - Biomol Ther (Seoul) (2014)

Neurite outgrowth in different experimental conditions. Panel A: control; Panel B: gp120 (500 pmol/L); Panel C: ddC (50 μmol/L); Panel D: gp120 (500 pmol/L)+ddC (50 μmol/L); Panel E: gp120 (500 pmol/L)+IGF-1 (20 nmol/L); Panel F: ddC (50 μmol/L)+IGF-1 (20 nmol/L); Panel G: gp120 (500 pmol/L)+ddC (50 μmol/L)+IGF-1 (20 nmol/L). A2-G2 are enlargements of small neurons in A1-G1 with thin arrows. A3-G3 are enlargements of large neurons in A1-G1 with thick arrows. Scale bar=50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4256033&req=5

f1-bt-22-532: Neurite outgrowth in different experimental conditions. Panel A: control; Panel B: gp120 (500 pmol/L); Panel C: ddC (50 μmol/L); Panel D: gp120 (500 pmol/L)+ddC (50 μmol/L); Panel E: gp120 (500 pmol/L)+IGF-1 (20 nmol/L); Panel F: ddC (50 μmol/L)+IGF-1 (20 nmol/L); Panel G: gp120 (500 pmol/L)+ddC (50 μmol/L)+IGF-1 (20 nmol/L). A2-G2 are enlargements of small neurons in A1-G1 with thin arrows. A3-G3 are enlargements of large neurons in A1-G1 with thick arrows. Scale bar=50 μm.
Mentions: To determine the total neurite length of each small DRG neuron, DRG neuronal cultures at 72 hours after treatment with different agents were processed for fluorescent labeling of MAP2. The total neurite length of each small DRG neuron (the diameter of neuronal cell body ≤25 μm) was measured. The mean total neurite length of small neurons in control group, gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L)+ddC (50 μmol/L), gp120 (500 pmol/L)+IGF-1 (20 nmol/L), ddC (50 μmol/L)+IGF-1 (20 nmol/L), and gp120 (500 pmol/L)+ddC (50 μmol/L)+IGF-1 (20 nmol/L) treated cultures was 296.3 μm ± 19.5 μm, 205.5 μm ± 20.7 μm, 178.6 μm ± 15.9 μm, 167.6 μm ± 15.9 μm, 246.2 μm ± 19.1 μm, 222.7 μm ± 13.3 μm, and 205.6 μm ± 14.52 μm, respectively. Exposure of gp120 and/or ddC induced neurite retraction of small DRG neurons (gp120, F=0.014, p=0.000; ddC, F=0.420, p=0.000; gp120+ddC, F=0.301, p=0.000). Interestingly, ddC exposure alone caused more severe neurite retraction of small DRG neurons compared with that in gp120-treated cultures (F=0.172, p=0.047). The combination of gp120 and ddC did not induce any further decreases in total neurite length of small DRG neurons compared with that in ddC-treated cultures suggesting a ceiling effect. Exogenous IGF-1 application could partially reverse the neurite retraction of small DRG neurons (gp120, F=0.009, p=0.012; ddC, F=0.079, p=0.001; gp120+ddC, F=0.047, p=0.004) (Fig. 1, 2).

Bottom Line: Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage.DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 μmol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours.These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Shandong University Affiliated Shandong Provincial Hospital, Jinan 250021.

ABSTRACT
Peripheral neuropathy induced by human immunodeficiency virus (HIV) infection and antiretroviral therapy is not only difficult to distinguish in clinical practice, but also difficult to relieve the pain symptoms by analgesics because of the severity of the disease at the later stage. Hence, to explore the mechanisms of HIV-related neuropathy and find new therapeutic options are particularly important for relieving neuropathic pain symptoms of the patients. In the present study, primary cultured embryonic rat dorsal root ganglion (DRG) neurons were used to determine the neurotoxic effects of HIV-gp120 protein and/or antiretroviral drug dideoxycytidine (ddC) and the therapeutic actions of insulin-like growth factor-1 (IGF-1) on gp120- or ddC-induced neurotoxicity. DRG neurons were exposed to gp120 (500 pmol/L), ddC (50 μmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L), gp120 (500 pmol/L) plus IGF-1 (20 nmol/L), ddC (50 μmol/L) plus IGF-1 (20 nmol/L), gp120 (500 pmol/L) plus ddC (50 μmol/L) plus IGF-1 (20 nmol/L), respectively, for 72 hours. The results showed that gp120 and/or ddC caused neurotoxicity of primary cultured DRG neurons. Interestingly, the severity of neurotoxicity induced by gp120 and ddC was different in different subpopulation of DRG neurons. gp120 mainly affected large diameter DRG neurons (>25 μm), whereas ddC mainly affected small diameter DRG neurons (≤25 μm). IGF-1 could reverse the neurotoxicity induced by gp120 and/or ddC on small, but not large, DRG neurons. These data provide new insights in elucidating the pathogenesis of HIV infection- or antiretroviral therapy-related peripheral neuropathy and facilitating the development of novel treatment strategies.

No MeSH data available.


Related in: MedlinePlus