Hippocampal Neuronal Apoptosis in Rat Offspring Due to Gestational Diabetes

Ghafari, Soraya; Asadi, Ebrahim; Shabani, Ronak; Golalipour, Mohammad Jafar

doi:10.4067/s0717-95022016000100029

Cited by 2 publications

(2 citation statements)

References 33 publications

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“…2 Hipokampus merupakan bagian otak yang mensintesis dan menghasilkan insulin tingkat tinggi yang berperan dalam memori dan pembelajaran. 3 Gangguan sintesis insulin dalam otak dapat menganggu fungsi neuron dan sinaptogenesis yang akan berkembang pada penyakit neurodegeneratif. 4 Studi terbaru menunjukkan bahwa obatobat pengurang rasa sakit akibat peradangan dan neuropatik, seperti obat antiepilepsi (OAE) dapat berperan sebagai bahan teratogenik.…”

Section: Pendahuluanunclassified

Pemberian Asam Valproat pada Induk Tikus Bunting Menghambat Sintesis Insulin pada Sel Otak Anak Tikus

Komariah¹,

Kiranadi²,

Winanto³

et al. 2017

mkb

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AbstrakAsam valproat memengaruhi aktivitas histone deacetylase yang berperan dalam ekspresi gen selama organogenesis. Insulin berperan dalam proliferasi dan diferensiasi sel-sel saraf dentate gyrus hipokampus. Penelitian ini bertujuan mempelajari pengaruh pemaparan asam valproat pada induk bunting terhadap ekspresi gen insulin pada dentate gyrus. Penelitian dilakukan di UPHL IPB pada bulan Mei 2015 hingga Desember 2016 dengan 84 ekor anak tikus yang dilahirkan oleh induk tikus kontrol yang diberi asam valproat 250 mg pada umur kebuntingan 10, 13, dan 16 hari digunakan untuk pengamatan kadar glukosa, insulin, DNA, RNA, dan rasio RNA/DNA serta pengamatan mikroskopis otak. Pengamatan dilakukan selang waktu empat minggu, dimulai dari umur 4 sampai 32 minggu. Anak tikus yang dilahirkan oleh induk tikus yang diberi asam valproat selama kebuntingan mempunyai kadar glukosa otak yang lebih tinggi (p<0,01) dan insulin yang lebih rendah (p<0,05). Selama periode pertumbuhan, anak tikus yang dilahirkan oleh induk tikus yang diberi asam valproat mengalami peningkatan kadar glukosa dan penurunan kadar insulin (p<0.05). Pengamatan mikroskopis sel-sel dentate gyrus menunjukkan degenerasi sel dan tidak terlihat reaksi imunoreaktif terhadap insulin, namun terjadi penurunan konsentrasi DNA, RNA, serta rasio RNA/DNA (p<0,05). Pemberian asam valproat pada induk tikus pada umur kebuntingan 10, 13, dan 16 hari memengaruhi organogenesis otak anak tikus sehingga menyebabkan kerusakan sel-sel saraf penghasil insulin otak yang ditunjukkan oleh penurunan sekresi dan kadar insulin. [MKB. 2017;49(3) Valproic Acid Administration in Pregnant Rats Inhibits Insulin Synthesis n in Brain Cells of the Offsprings AbstractValproic acid affects the activity of histone deacetylase which eventually affects gene expression during organogenesis. Insulin plays a role in regulating the proliferation and differentiation of the dentate gyrus. This experiment was designed to study the effects of valproic acid administration on the expression of insulin gene in the dentate gyrus of pregnant rats. This study was carried out at the Laboratory Animal Management Unit (UPHL) of Bogor Agricultural University from May 2015 to December 2016, with eighty four newborn rats from control rats and VA-administered rats at the age of 10, 13, and 16 days of pregnancy. The measurements were done for glucose, insulin, DNA, and RNA concentrations in dentate gyrus and to observe the microscopic condition of the brain at the ages of 4 to 32 weeks with 4 weeks interval. Rats born form mothers administered by 250 mg valproic acid during pregnancy had higher glucose concentrations (p<0.01) and lower insulin concentrations (p<0.05) in the dentate gyrus. During the post-natal growth phase, rats born from mothers administered with valproic acid had increased glucose concentrations and decreased insulin concentrations (p<0.05). Microscopic observations of the dentate gyrus showed degeneration of nerve cells with no immunoreaction to insulin was seen in dentate gyrus cells. However, the co...

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Section: Pendahuluanunclassified

Pemberian Asam Valproat pada Induk Tikus Bunting Menghambat Sintesis Insulin pada Sel Otak Anak Tikus

Komariah¹,

Kiranadi²,

Winanto³

et al. 2017

mkb

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“…Apoptosis is responsible for several diabetes complications, such as diabetic neuropathy (7). In diabetes mellitus, the pathology of the central nervous system is related to hyperglycemia and the lack of insulin (8).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of Bax/Bcl-2 Expression During Apoptosis in the Hippocampus of Diabetic Male Wistar Rats: Ameliorative Effects of Peganum harmala Seed Extract

et al. 2023

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Background: Apoptosis is proposed as a possible mechanism for diabetes-induced hippocampal neuronal cell death. Numerous studies have suggested that the therapeutic properties of plants, such as antioxidant and anti-apoptotic, are effective in improving the complications of diabetes in the hippocampus. Objectives: This study aimed to evaluate the anti-apoptotic properties of Peganum harmala (P. harmala) in the brain hippocampal cells of diabetic rats. Methods: In this experimental study, 48 male Wistar rats were divided into six groups (n = 8) as follows: Control (C), diabetic (D), harmine (H), diabetic plus harmine (DH), seed extract (S), and diabetic plus seed extract (DS). A single dose of streptozotocin (STZ) (60 mg/kg) was enough to cause diabetes. Seed extract and harmine were given at 150 mg/kg and 6.5 mg/kg, respectively (daily by oral gavage for 28 days). The glucose levels in the blood were measured, and the histological staining of the hippocampus was examined. Percentages of apoptotic hippocampal cells were identified with flow cytometry. Bax and Bcl-2 expression was assayed via Real time- polymerase chain reaction (PCR) and Western blot. Results: In DH (P = 0.001) and DS (P = 0.01) rats, the mean fasting blood glucose level significantly reduced compared with the D group. Bax and Bcl-2 expression at both mRNA and protein levels significantly differed between the D group and other groups (P = 0.01). Harmine and the seed extract considerably reduced the Bax/Bcl-2 ratio in the hippocampal cells compared to the D group (P = 0.001). Conclusions: Streptozotocin-induced apoptosis in the hippocampus of diabetic rats was reduced by administering the seed extract of Peganum harmala. The P. harmala seed extract and its active ingredient, harmine, could be used as anti-apoptotic drugs.

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Hippocampal Neuronal Apoptosis in Rat Offspring Due to Gestational Diabetes

Cited by 2 publications

References 33 publications

Pemberian Asam Valproat pada Induk Tikus Bunting Menghambat Sintesis Insulin pada Sel Otak Anak Tikus

Pemberian Asam Valproat pada Induk Tikus Bunting Menghambat Sintesis Insulin pada Sel Otak Anak Tikus

Downregulation of Bax/Bcl-2 Expression During Apoptosis in the Hippocampus of Diabetic Male Wistar Rats: Ameliorative Effects of Peganum harmala Seed Extract

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