Effects of BDNF deficiency and endoplasmic reticulum stress on the GABAergic system
Öz
Purpose: Protective pathways against endoplasmic reticulum stress in neurons are activated via brain-derived neurotrophic factor. However, it is not known how the inhibitory intermediate neuron types expressing the different Ca2+-binding proteins of GABAergic system will be affected with changes in Ca2+ homeostasis, in conditions of chronic reduction of brain-derived neurotrophic factor and endoplasmic reticulum stress. The study was planned to reveal the interaction of these factors.
Materials and methods: 6-8 months old (30-40 g), wild-type (WT) and brain-derived neurotrophic factor heterozygous (BDNF(+/-)) male mice were used and 4 groups were formed. Groups 3 and 4 were treated with a single dose of tunicamycin to induce endoplasmic reticulum stress. On the 3rd day of tunicamycin injection, animals were sacrificed and blood and brain tissues were taken. In serum samples BDNF, in tissue homogenates GRP78, CHOP, Caspase-12, parvalbumin, calretinin, calbindin, GAD65 and GAD67 levels were investigated by ELISA method. One-way ANOVA and Tukey post-hoc tests were used for statistical evaluation.
Results: Serum BDNF levels were significantly lower in BDNF(+/-) and tunicamycin-treated BDNF(+/-) groups. Caspase-12 and CHOP levels significantly increased with tunicamycin injection. Calbindin level decreased significantly with endoplasmic reticulum stress. GAD65 and GAD67 levels were similar in WT and BDNF(+/-) groups. However, GAD65 level was significantly decreased during endoplasmic reticulum stress in WT and BDNF(+/-) groups.
Conclusion: Endoplasmic reticulum stress caused a significant decrease in glutamic acid decarboxylase GAD65 isoform and caldindin levels. This result indicates that the sensitivity of varied intermediate neurons in GABAergic system to endoplasmic reticulum stress may be different.
Anahtar Kelimeler
BDNF, Endoplasmic reticulum stress, Calcium homeostasis, GABA
Destekleyen Kurum
Giresun Üniversitesi
Proje Numarası
SAĞ-BAP-A-230218-85
Kaynakça
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