https://orcid.org/0000-0002-0944-6397
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ABSTRACT
Background
Post-stroke depression (PSD), the most frequent psychiatric complication following stroke, could have a negative impact on the recuperation of stroke patients. Hyperhomocysteinemia (HHCY) has been reported to be a modifiable risk factor of stroke.
Objective
The study tries to explore the effect of HHCY on PSD and the role of N-methyl-d-aspartate receptors (NMDARs)-mediated synaptic alterations.
Methods
Forty-five adult male Sprague–Dawley rats were randomly allocated into five groups: sham operation group, middle cerebral artery occlusion group (MCAO), HCY-treated MCAO group HCY and MK-801 co-treated MCAO group and MK-801-treated MCAO group. 1.6 mg/kg/d D, L-HCY was administered by tail vein injection for 28 d prior to SHAM or MCAO operationand up to 14 d after surgery. The MK-801 (3 mg/kg) was administered by intraperitoneal injection 15 min prior to MCAO operation.
Results
HCY treatment aggravated depressive-like disorders of post-stroke rats by the open field test and sucrose preference test. Further, HCY significantly decreased central monoamines levels in the MCAO rats by HPLC. The transmission electron microscopy results showed that the number of synapses and the area of postsynaptic density decreased in the hippocampus of the HCY-treated MCAO rats. Additionally, HCY augmented ischemia-induced up-regulation of NMDARs, decreased the levels of synaptic structure-related marker PSD-95and the synaptic transmission-associated synaptic proteins (VGLUT1, SNAP-25 and Complexin Ι/ΙΙ). These effects of HCY were partly reversed by the NMDA antagonist MK-801.
Conclusions
The current study suggested that NMDARs-mediated synaptic plasticity may be involved in the adverse effect of HCY on PSD.
Acknowledgements
All authors read and approved the final manuscript.
Data availability statement
The datasets and/or analysed during the current study available from the corresponding author on request.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
Notes on contributors
Mengying Wang
Mengying Wang, MM, the Department of Nutrition and Food Science, Tianjin Medical University (China). Her research interests are in nutrition and central nervous system diseases.
Xiaoshan Liang
Xiaoshan Liang, MD candidate in the Department of Nutrition and Food Science of Tianjin Medical University (China). She has published six academic papers related to ischemic stroke.
Qiang Zhang
Qiang Zhang, Associate Professor in the Department of Occupational health and Environmental Health, Tianjin Medical University (China). His research interests focus on nutrition-environment interactions in disease development.
Suhui Luo
Suhui Luo, MM, technician in the Department of Nutrition and Food Science of Tianjin Medical University (China).
Huan Liu
Huan Liu, professor of Department of Nutrition and Food Science in Tianjin Medical University (China). Her research interests are in nutrition and chronic diseases. She has presided over two National Natural Science Foundation of China projects and participated in three.
Xuan Wang
Xuan Wang, MD, lecturer in the Department of Nutrition and Food Science of Tianjin Medical University (China). Her research interests are in nutrition and chronic diseases.
Na Sai
Na Sai, PhD., lecturer in the Department of Nutrition and Food Science of Tianjin Medical University (China). Her research interests focus on food ingredient testing.
Xumei Zhang
Xumei Zhang, PhD., professor of Department of Nutrition and Food Science in Tianjin Medical University (China). She has presided over four National Natural Science Foundation of China projects and published more than 70 academic papers involved in nutrition, brain aging and neurodegeneration.