TY - JOUR
T1 - Methylcyclopentadienyl Manganese Tricarbonyl Alter Behavior and Cause Ultrastructural Changes in the Substantia Nigra of Rats
T2 - Comparison with Inorganic Manganese Chloride
AU - Zhu, Qi feng
AU - Lu, Li li
AU - Fang, Yuan yuan
AU - Wu, Jie
AU - Huang, Zhao ying
AU - Zheng, Xiao wei
AU - Song, Han xiao
AU - Aschner, Michael
AU - Song, Ce
AU - Jiang, Yue ming
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2022/8
Y1 - 2022/8
N2 - The antiknock additive methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese(Mn) compound. Mn neurotoxicity caused by occupational Mn exposure (mostly inorganic MnCl2) is associated with motor and cognitive disturbances, referred to as Manganism. However, the impact of environmentally relevant Mn exposure on MMT-induced Manganism is poorly understood. In this investigation, we studied the effects of MMT on motor function and brain structure, and compared its effects with those of inorganic MnCl2. After adaptive feeding for 7 days, male and female Sprague–Dawley (SD) rats in the MMT-treated groups and positive control group were treated for 8 weeks with MMT (1, 2 and 4 mg/kg/i.g.) or MnCl2·4H2O (200 mg/kg/i.g.). Mn content in blood, liver, spleen and distinct brain regions was determined by inductively coupled plasma-mass spectrometer (ICP-MS). We found that MMT and MnCl2 exposure led to slower body-weight-gain in female rats, impaired motor and balance function and spatial learning and memory both in male and female rats. HE staining showed that MMT and MnCl2 led to altered structure of the substantia nigra pars compacta (SNpc), and Nissl staining corroborated MMT’s propensity to damage the SNpc both in male and female rat. In addition, Immunostaining of the SNpc showed decreased TH-positive neurons in MMT- and MnCl2-treated rats, concomitant with Iba1 activation in microglia. Moreover, no statistically significant difference was noted between the rats in the H-MMT and MnCl2 groups. In summary, these findings suggest that MMT and MnCl2 exposure cause ultrastructural changes in the SNpc neurons culminating in altered motor behavior and cognition, suggesting that altered SNpc structure and function may underline the motor and cognitive deficits inherent to Manganism, and accounting for MMT and MnCl2’s manifestations of atypical parkinsonism.
AB - The antiknock additive methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese(Mn) compound. Mn neurotoxicity caused by occupational Mn exposure (mostly inorganic MnCl2) is associated with motor and cognitive disturbances, referred to as Manganism. However, the impact of environmentally relevant Mn exposure on MMT-induced Manganism is poorly understood. In this investigation, we studied the effects of MMT on motor function and brain structure, and compared its effects with those of inorganic MnCl2. After adaptive feeding for 7 days, male and female Sprague–Dawley (SD) rats in the MMT-treated groups and positive control group were treated for 8 weeks with MMT (1, 2 and 4 mg/kg/i.g.) or MnCl2·4H2O (200 mg/kg/i.g.). Mn content in blood, liver, spleen and distinct brain regions was determined by inductively coupled plasma-mass spectrometer (ICP-MS). We found that MMT and MnCl2 exposure led to slower body-weight-gain in female rats, impaired motor and balance function and spatial learning and memory both in male and female rats. HE staining showed that MMT and MnCl2 led to altered structure of the substantia nigra pars compacta (SNpc), and Nissl staining corroborated MMT’s propensity to damage the SNpc both in male and female rat. In addition, Immunostaining of the SNpc showed decreased TH-positive neurons in MMT- and MnCl2-treated rats, concomitant with Iba1 activation in microglia. Moreover, no statistically significant difference was noted between the rats in the H-MMT and MnCl2 groups. In summary, these findings suggest that MMT and MnCl2 exposure cause ultrastructural changes in the SNpc neurons culminating in altered motor behavior and cognition, suggesting that altered SNpc structure and function may underline the motor and cognitive deficits inherent to Manganism, and accounting for MMT and MnCl2’s manifestations of atypical parkinsonism.
KW - Dopaminergic neuron loss
KW - Iba1
KW - MMT
KW - Microglia
KW - MnCl
KW - Rats
KW - Substantia nigra pars compacta (SNpc)
KW - motor behavior and cognition
UR - http://www.scopus.com/inward/record.url?scp=85129383788&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85129383788&partnerID=8YFLogxK
U2 - 10.1007/s11064-022-03606-z
DO - 10.1007/s11064-022-03606-z
M3 - Article
C2 - 35513760
AN - SCOPUS:85129383788
SN - 0364-3190
VL - 47
SP - 2198
EP - 2210
JO - Neurochemical Research
JF - Neurochemical Research
IS - 8
ER -