Pyridoxine Deficiency Exacerbates Neuronal Damage after Ischemia by Increasing Oxidative Stress and Reduces Proliferating Cells and Neuroblasts in the Gerbil Hippocampus.

Abstract

We investigated the effects of pyridoxine deficiency on ischemic neuronal death in the hippocampus of gerbil (n = 5 per group). Serum pyridoxal 5'-phosphate levels were significantly decreased in Pyridoxine-deficient diet (PDD)-fed gerbils, while homocysteine levels were significantly increased in sham- and ischemia-operated gerbils. PDD-fed gerbil showed a reduction in neuronal nuclei (NeuN)-immunoreactive neurons in the medial part of the hippocampal CA1 region three days after. Reactive astrocytosis and microgliosis were found in PDD-fed gerbils, and transient ischemia caused the aggregation of activated microglia in the stratum pyramidale three days after ischemia. Lipid peroxidation was prominently increased in the hippocampus and was significantly higher in PDD-fed gerbils than in Control diet (CD)-fed gerbils after ischemia. In contrast, pyridoxine deficiency decreased the proliferating cells and neuroblasts in the dentate gyrus in sham- and ischemia-operated gerbils. Nuclear factor erythroid-2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF) levels also significantly decreased in PDD-fed gerbils sham 24 h after ischemia. These results suggest that pyridoxine deficiency accelerates neuronal death by increasing serum homocysteine levels and lipid peroxidation, and by decreasing Nrf2 levels in the hippocampus. Additionally, it reduces the regenerated potentials in hippocampus by decreasing BDNF levels. Collectively, pyridoxine is an essential element in modulating cell death and hippocampal neurogenesis after ischemia.

• Authors: Hyo Young Jung, Woosuk Kim, Kyu Ri Hahn, Min Soo Kang, Tae Hyeong Kim, Hyun Jung Kwon, Sung Min Nam, Jin Young Chung, Jung Hoon Choi, Yeo Sung Yoon, Dae Won Kim, Dae Young Yoo, In Koo Hwang
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 15 (Aug 04 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32759679 (Publication Type: Journal Article)

Chemical References

• Brain-Derived Neurotrophic Factor
• NF-E2-Related Factor 2
• Pyridoxine

Topics

• Animals
• Brain Ischemia (genetics, metabolism, pathology)
• Brain-Derived Neurotrophic Factor (genetics)
• Cell Proliferation (drug effects)
• Diet
• Gerbillinae (genetics, metabolism)
• Hippocampus (metabolism)
• NF-E2-Related Factor 2 (genetics)
• Neural Stem Cells (metabolism, pathology)
• Neurons (metabolism)
• Oxidative Stress (genetics)
• Pyridoxine (deficiency, metabolism, pharmacology)