Maternal Zinc Diet Impairs Learning and Memory in Offspring Rats through the CREB/BDNF Pathway
BACKGROUND: Zinc released into the synaptic cleft able to modulate various signaling pathways, including brain derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB). Zinc binding to its receptor, G-protein coupled receptor 39 (GPR39), may trigger biochemical pathwa...
| मुख्य लेखकों: | , , , |
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| स्वरूप: | लेख |
| भाषा: | English |
| प्रकाशित: |
Secretariat of The Indonesian Biomedical Journal
2024-06-01
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| श्रृंखला: | Indonesian Biomedical Journal |
| ऑनलाइन पहुंच: | https://inabj.org/index.php/ibj/article/view/3021 |
| _version_ | 1827211802669219840 |
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| author | Novi Dewi Tanjung Nieka Adhara Wahono Ninik Mudjihartini Ani Retno Prijanti |
| author_facet | Novi Dewi Tanjung Nieka Adhara Wahono Ninik Mudjihartini Ani Retno Prijanti |
| author_sort | Novi Dewi Tanjung |
| collection | DOAJ |
| description | BACKGROUND: Zinc released into the synaptic cleft able to modulate various signaling pathways, including brain derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB). Zinc binding to its receptor, G-protein coupled receptor 39 (GPR39), may trigger biochemical pathways leading to cAMP response element binding protein (CREB)-dependent gene transcription that subsequently promotes BDNF upregulation. Therefore, zinc dyshomeostasis should be considered as a condition that induces disruption of CREB/BDNF signaling. This study was conducted to examine the effect of maternal zinc diet on hippocampal expression levels of CREB and BDNF in offspring.
METHODS: One-day pregnant rats were randomly divided into five groups: zinc-deficient (D), zinc-restricted (R), zinc-adequate (A), zinc-supplemented (S), and excess zinc-supplemented (ES). The groups had different zinc diets during pregnancy and lactation. The behavioral function of the offspring was tested with Y-maze at the 43th postnatal. Hippocampus was isolated, BDNF was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), and CREB was examined using sandwich enzyme-linked immunosorbent assay (ELISA).
RESULTS: Spatial working memory measurement demonstrated that D and ES group exhibited a significantly lower spontaneous alternation than other groups. The qRT-PCR and ELISA analysis revealed the hippocampal expression level of BDNF and CREB decreased in groups D and ES, but tended to increase in groups R and S, until the highest expression peak was found in group A.
CONCLUSION: High and low intake of zinc induces lower expression of BDNF and CREB in hippocampus, which further impairs learning and memory. Our findings suggest the signaling pathway of CREB/BDNF is involved in zinc dyshomeostasis-induced cognitive impairments.
KEYWORDS: hippocampus, BDNF, CREB, TrkB, GPR39, zinc, diet, LTP |
| first_indexed | 2025-03-21T13:49:26Z |
| format | Article |
| id | doaj.art-6c9e799c675e4f5087d404f2f0018d0e |
| institution | Directory Open Access Journal |
| issn | 2085-3297 2355-9179 |
| language | English |
| last_indexed | 2025-03-21T13:49:26Z |
| publishDate | 2024-06-01 |
| publisher | Secretariat of The Indonesian Biomedical Journal |
| record_format | Article |
| series | Indonesian Biomedical Journal |
| spelling | doaj.art-6c9e799c675e4f5087d404f2f0018d0e2024-06-26T06:51:23ZengSecretariat of The Indonesian Biomedical JournalIndonesian Biomedical Journal2085-32972355-91792024-06-011632283610.18585/inabj.v16i3.3021575Maternal Zinc Diet Impairs Learning and Memory in Offspring Rats through the CREB/BDNF PathwayNovi Dewi Tanjung0Nieka Adhara Wahono1Ninik Mudjihartini2Ani Retno Prijanti3Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No. 6, JakartaDepartment of Pediatric Dentistry, Faculty of Dentistry, Universitas Indonesia, Jl. Salemba Raya IV No.2, JakartaDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No. 6, JakartaDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jl. Salemba Raya No. 6, JakartaBACKGROUND: Zinc released into the synaptic cleft able to modulate various signaling pathways, including brain derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB). Zinc binding to its receptor, G-protein coupled receptor 39 (GPR39), may trigger biochemical pathways leading to cAMP response element binding protein (CREB)-dependent gene transcription that subsequently promotes BDNF upregulation. Therefore, zinc dyshomeostasis should be considered as a condition that induces disruption of CREB/BDNF signaling. This study was conducted to examine the effect of maternal zinc diet on hippocampal expression levels of CREB and BDNF in offspring. METHODS: One-day pregnant rats were randomly divided into five groups: zinc-deficient (D), zinc-restricted (R), zinc-adequate (A), zinc-supplemented (S), and excess zinc-supplemented (ES). The groups had different zinc diets during pregnancy and lactation. The behavioral function of the offspring was tested with Y-maze at the 43th postnatal. Hippocampus was isolated, BDNF was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), and CREB was examined using sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Spatial working memory measurement demonstrated that D and ES group exhibited a significantly lower spontaneous alternation than other groups. The qRT-PCR and ELISA analysis revealed the hippocampal expression level of BDNF and CREB decreased in groups D and ES, but tended to increase in groups R and S, until the highest expression peak was found in group A. CONCLUSION: High and low intake of zinc induces lower expression of BDNF and CREB in hippocampus, which further impairs learning and memory. Our findings suggest the signaling pathway of CREB/BDNF is involved in zinc dyshomeostasis-induced cognitive impairments. KEYWORDS: hippocampus, BDNF, CREB, TrkB, GPR39, zinc, diet, LTPhttps://inabj.org/index.php/ibj/article/view/3021 |
| spellingShingle | Novi Dewi Tanjung Nieka Adhara Wahono Ninik Mudjihartini Ani Retno Prijanti Maternal Zinc Diet Impairs Learning and Memory in Offspring Rats through the CREB/BDNF Pathway Indonesian Biomedical Journal |
| title | Maternal Zinc Diet Impairs Learning and Memory in Offspring Rats through the CREB/BDNF Pathway |
| title_full | Maternal Zinc Diet Impairs Learning and Memory in Offspring Rats through the CREB/BDNF Pathway |
| title_fullStr | Maternal Zinc Diet Impairs Learning and Memory in Offspring Rats through the CREB/BDNF Pathway |
| title_full_unstemmed | Maternal Zinc Diet Impairs Learning and Memory in Offspring Rats through the CREB/BDNF Pathway |
| title_short | Maternal Zinc Diet Impairs Learning and Memory in Offspring Rats through the CREB/BDNF Pathway |
| title_sort | maternal zinc diet impairs learning and memory in offspring rats through the creb bdnf pathway |
| url | https://inabj.org/index.php/ibj/article/view/3021 |
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