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Tricyclic Antidepressants Amitriptyline and Desipramine Induced Neurotoxicity Associated with Parkinson's Disease.

Lee MY, Hong S, Kim N, Shin KS, Kang SJ - Mol. Cells (2015)

Bottom Line: In the present study, we examined whether tricyclic antidepressants amitriptyline and desipramine can induce dopaminergic cell damage, both in vitro and in vivo.We found that amitriptyline and desipramine induced mitochondria-mediated neurotoxicity and oxidative stress in SH-SY5Y cells.Our results suggest that amitriptyline and desipramine may induce PD-associated neurotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Sejong University, Seoul 143-747, Korea.

ABSTRACT
Recent studies report that a history of antidepressant use is strongly correlated with the occurrence of Parkinson's disease (PD). However, it remains unclear whether antidepressant use can be a causative factor for PD. In the present study, we examined whether tricyclic antidepressants amitriptyline and desipramine can induce dopaminergic cell damage, both in vitro and in vivo. We found that amitriptyline and desipramine induced mitochondria-mediated neurotoxicity and oxidative stress in SH-SY5Y cells. When injected into mice on a subchronic schedule, amitriptyline induced movement deficits in the pole test, which is known to detect nigrostriatal dysfunction. In addition, the number of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta was reduced in amitriptyline-injected mice. Our results suggest that amitriptyline and desipramine may induce PD-associated neurotoxicity.

No MeSH data available.


Related in: MedlinePlus

Subchronically injected amitriptyline induced TH-positive neuronal loss in the SNpc. To examine the in vivo effect of amitriptyline, mice were intraperitoneally injected with amitriptyline (20 mg/kg body weight) twice a week for 4 weeks. Brain tissue sections were prepared from the midbrain area of control vehicle- or amitriptyline-injected mice and immunostained using anti-TH antibodies. Representative immunohistochemistry photographs are shown in (A). (B) The number of TH-positive cells was counted from each SNpc area. At least ten sections from each mouse were counted (n = 5, *p < 0.5 vs. vehicle injected).
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f5-molce-38-8-734: Subchronically injected amitriptyline induced TH-positive neuronal loss in the SNpc. To examine the in vivo effect of amitriptyline, mice were intraperitoneally injected with amitriptyline (20 mg/kg body weight) twice a week for 4 weeks. Brain tissue sections were prepared from the midbrain area of control vehicle- or amitriptyline-injected mice and immunostained using anti-TH antibodies. Representative immunohistochemistry photographs are shown in (A). (B) The number of TH-positive cells was counted from each SNpc area. At least ten sections from each mouse were counted (n = 5, *p < 0.5 vs. vehicle injected).

Mentions: To examine whether TCA can induce neurotoxicity in dopaminergic neurons in vivo, mice were intraperitoneally injected with 20 mg/kg of amitriptyline on a subchronic schedule (twice a week for 4 weeks) and the number of TH-positive cells in the SNpc was counted. As can be seen in Fig. 5, the number of TH-positive cells in the SNpc of amitriptyline-injected mice was significantly reduced compared with vehicle-injected mice. About 35% of the TH-positive neurons were lost in the SNpc of the amitriptyline-injected mice, suggesting that the TCA can induce cytotoxicity of dopaminergic neurons in the brain area affected in PD.


Tricyclic Antidepressants Amitriptyline and Desipramine Induced Neurotoxicity Associated with Parkinson's Disease.

Lee MY, Hong S, Kim N, Shin KS, Kang SJ - Mol. Cells (2015)

Subchronically injected amitriptyline induced TH-positive neuronal loss in the SNpc. To examine the in vivo effect of amitriptyline, mice were intraperitoneally injected with amitriptyline (20 mg/kg body weight) twice a week for 4 weeks. Brain tissue sections were prepared from the midbrain area of control vehicle- or amitriptyline-injected mice and immunostained using anti-TH antibodies. Representative immunohistochemistry photographs are shown in (A). (B) The number of TH-positive cells was counted from each SNpc area. At least ten sections from each mouse were counted (n = 5, *p < 0.5 vs. vehicle injected).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4546946&req=5

f5-molce-38-8-734: Subchronically injected amitriptyline induced TH-positive neuronal loss in the SNpc. To examine the in vivo effect of amitriptyline, mice were intraperitoneally injected with amitriptyline (20 mg/kg body weight) twice a week for 4 weeks. Brain tissue sections were prepared from the midbrain area of control vehicle- or amitriptyline-injected mice and immunostained using anti-TH antibodies. Representative immunohistochemistry photographs are shown in (A). (B) The number of TH-positive cells was counted from each SNpc area. At least ten sections from each mouse were counted (n = 5, *p < 0.5 vs. vehicle injected).
Mentions: To examine whether TCA can induce neurotoxicity in dopaminergic neurons in vivo, mice were intraperitoneally injected with 20 mg/kg of amitriptyline on a subchronic schedule (twice a week for 4 weeks) and the number of TH-positive cells in the SNpc was counted. As can be seen in Fig. 5, the number of TH-positive cells in the SNpc of amitriptyline-injected mice was significantly reduced compared with vehicle-injected mice. About 35% of the TH-positive neurons were lost in the SNpc of the amitriptyline-injected mice, suggesting that the TCA can induce cytotoxicity of dopaminergic neurons in the brain area affected in PD.

Bottom Line: In the present study, we examined whether tricyclic antidepressants amitriptyline and desipramine can induce dopaminergic cell damage, both in vitro and in vivo.We found that amitriptyline and desipramine induced mitochondria-mediated neurotoxicity and oxidative stress in SH-SY5Y cells.Our results suggest that amitriptyline and desipramine may induce PD-associated neurotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Sejong University, Seoul 143-747, Korea.

ABSTRACT
Recent studies report that a history of antidepressant use is strongly correlated with the occurrence of Parkinson's disease (PD). However, it remains unclear whether antidepressant use can be a causative factor for PD. In the present study, we examined whether tricyclic antidepressants amitriptyline and desipramine can induce dopaminergic cell damage, both in vitro and in vivo. We found that amitriptyline and desipramine induced mitochondria-mediated neurotoxicity and oxidative stress in SH-SY5Y cells. When injected into mice on a subchronic schedule, amitriptyline induced movement deficits in the pole test, which is known to detect nigrostriatal dysfunction. In addition, the number of tyrosine hydroxylase-positive neurons in the substantia nigra pars compacta was reduced in amitriptyline-injected mice. Our results suggest that amitriptyline and desipramine may induce PD-associated neurotoxicity.

No MeSH data available.


Related in: MedlinePlus