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Capsaicin prevents degeneration of dopamine neurons by inhibiting glial activation and oxidative stress in the MPTP model of Parkinson's disease

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ABSTRACT

The effects of capsaicin (CAP), a transient receptor potential vanilloid subtype 1 (TRPV1) agonist, were determined on nigrostriatal dopamine (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). The results showed that TRPV1 activation by CAP rescued nigrostriatal DA neurons, enhanced striatal DA functions and improved behavioral recovery in MPTP-treated mice. CAP neuroprotection was associated with reduced expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and reactive oxygen species/reactive nitrogen species from activated microglia-derived NADPH oxidase, inducible nitric oxide synthase or reactive astrocyte-derived myeloidperoxidase. These beneficial effects of CAP were reversed by treatment with the TRPV1 antagonists capsazepine and iodo-resiniferatoxin, indicating TRPV1 involvement. This study demonstrates that TRPV1 activation by CAP protects nigrostriatal DA neurons via inhibition of glial activation-mediated oxidative stress and neuroinflammation in the MPTP mouse model of PD. These results suggest that CAP and its analogs may be beneficial therapeutic agents for the treatment of PD and other neurodegenerative disorders that are associated with neuroinflammation and glial activation-derived oxidative damage.

No MeSH data available.


Related in: MedlinePlus

Capsaicin (CAP) attenuates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in the substantia nigra (SN) in vivo. Seven days after the last MPTP injection, animals were killed, and their brain tissues were processed for immunostaining with a tyrosine hydroxylase (TH) antibody for dopamine (DA) neurons: phosphate-buffered saline (PBS) (a, b), CAP (0.5 mg kg−1) alone (c, d), MPTP (e, f), MPTP+CAP (g, h), MPTP+CAP+capsazepine (CZP) (i, j) and MPTP+CAP+iodo-resiniferatoxin (I-RTX) (k, l). (m) The numbers of TH-positive cells in the SNpc. Bars represent the means±s.e.m. of five to six animals per group. *P<0.001 significantly different from control, #P<0.001, significantly different from MPTP. &P<0.001 significantly different from MPTP and CAP. SNpc, substantia nigra pars compacta; SNr, substantia nigra reticulata; VTA, ventral tegmental area. Scale bars, 300 μm (a, c, e, g, i, k); 50 μm (b, d, f, h, j, k).
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fig1: Capsaicin (CAP) attenuates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in the substantia nigra (SN) in vivo. Seven days after the last MPTP injection, animals were killed, and their brain tissues were processed for immunostaining with a tyrosine hydroxylase (TH) antibody for dopamine (DA) neurons: phosphate-buffered saline (PBS) (a, b), CAP (0.5 mg kg−1) alone (c, d), MPTP (e, f), MPTP+CAP (g, h), MPTP+CAP+capsazepine (CZP) (i, j) and MPTP+CAP+iodo-resiniferatoxin (I-RTX) (k, l). (m) The numbers of TH-positive cells in the SNpc. Bars represent the means±s.e.m. of five to six animals per group. *P<0.001 significantly different from control, #P<0.001, significantly different from MPTP. &P<0.001 significantly different from MPTP and CAP. SNpc, substantia nigra pars compacta; SNr, substantia nigra reticulata; VTA, ventral tegmental area. Scale bars, 300 μm (a, c, e, g, i, k); 50 μm (b, d, f, h, j, k).

Mentions: Similar to our recent reports,21, 22 the TH immunohistochemical analysis revealed that MPTP exerted significant neurotoxicity on TH-positive cell bodies in the SN (Figure 1e and f) and its fibers in the STR (Figure 2c) at 7 days compared with control PBS (intact)-treated mice (Figures 1a,b and 2a). The results of the stereological counts and densitometric analyses showed a significant reduction in the number of TH-positive cells by 72% in the SN (Figure 1m) and the density of TH-positive fibers by 77% in the STR (Figure 2g) in the MPTP-treated mice compared with PBS-treated control mice.


Capsaicin prevents degeneration of dopamine neurons by inhibiting glial activation and oxidative stress in the MPTP model of Parkinson's disease
Capsaicin (CAP) attenuates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in the substantia nigra (SN) in vivo. Seven days after the last MPTP injection, animals were killed, and their brain tissues were processed for immunostaining with a tyrosine hydroxylase (TH) antibody for dopamine (DA) neurons: phosphate-buffered saline (PBS) (a, b), CAP (0.5 mg kg−1) alone (c, d), MPTP (e, f), MPTP+CAP (g, h), MPTP+CAP+capsazepine (CZP) (i, j) and MPTP+CAP+iodo-resiniferatoxin (I-RTX) (k, l). (m) The numbers of TH-positive cells in the SNpc. Bars represent the means±s.e.m. of five to six animals per group. *P<0.001 significantly different from control, #P<0.001, significantly different from MPTP. &P<0.001 significantly different from MPTP and CAP. SNpc, substantia nigra pars compacta; SNr, substantia nigra reticulata; VTA, ventral tegmental area. Scale bars, 300 μm (a, c, e, g, i, k); 50 μm (b, d, f, h, j, k).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382554&req=5

fig1: Capsaicin (CAP) attenuates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in the substantia nigra (SN) in vivo. Seven days after the last MPTP injection, animals were killed, and their brain tissues were processed for immunostaining with a tyrosine hydroxylase (TH) antibody for dopamine (DA) neurons: phosphate-buffered saline (PBS) (a, b), CAP (0.5 mg kg−1) alone (c, d), MPTP (e, f), MPTP+CAP (g, h), MPTP+CAP+capsazepine (CZP) (i, j) and MPTP+CAP+iodo-resiniferatoxin (I-RTX) (k, l). (m) The numbers of TH-positive cells in the SNpc. Bars represent the means±s.e.m. of five to six animals per group. *P<0.001 significantly different from control, #P<0.001, significantly different from MPTP. &P<0.001 significantly different from MPTP and CAP. SNpc, substantia nigra pars compacta; SNr, substantia nigra reticulata; VTA, ventral tegmental area. Scale bars, 300 μm (a, c, e, g, i, k); 50 μm (b, d, f, h, j, k).
Mentions: Similar to our recent reports,21, 22 the TH immunohistochemical analysis revealed that MPTP exerted significant neurotoxicity on TH-positive cell bodies in the SN (Figure 1e and f) and its fibers in the STR (Figure 2c) at 7 days compared with control PBS (intact)-treated mice (Figures 1a,b and 2a). The results of the stereological counts and densitometric analyses showed a significant reduction in the number of TH-positive cells by 72% in the SN (Figure 1m) and the density of TH-positive fibers by 77% in the STR (Figure 2g) in the MPTP-treated mice compared with PBS-treated control mice.

View Article: PubMed Central - PubMed

ABSTRACT

The effects of capsaicin (CAP), a transient receptor potential vanilloid subtype 1 (TRPV1) agonist, were determined on nigrostriatal dopamine (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). The results showed that TRPV1 activation by CAP rescued nigrostriatal DA neurons, enhanced striatal DA functions and improved behavioral recovery in MPTP-treated mice. CAP neuroprotection was associated with reduced expression of proinflammatory cytokines (tumor necrosis factor-&alpha; and interleukin-1&beta;) and reactive oxygen species/reactive nitrogen species from activated microglia-derived NADPH oxidase, inducible nitric oxide synthase or reactive astrocyte-derived myeloidperoxidase. These beneficial effects of CAP were reversed by treatment with the TRPV1 antagonists capsazepine and iodo-resiniferatoxin, indicating TRPV1 involvement. This study demonstrates that TRPV1 activation by CAP protects nigrostriatal DA neurons via inhibition of glial activation-mediated oxidative stress and neuroinflammation in the MPTP mouse model of PD. These results suggest that CAP and its analogs may be beneficial therapeutic agents for the treatment of PD and other neurodegenerative disorders that are associated with neuroinflammation and glial activation-derived oxidative damage.

No MeSH data available.


Related in: MedlinePlus