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All Journal Indonesian Journal of Biotechnology Jurnal Farmasi Sains dan Komunitas
Nunung Yuniarti
Laboratory of Pharmacology and Toxicology, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia
Biochemistry, Genetics & Molecular Biology Immunology & microbiology Materials Science & Nanotechnology Medicine & Pharmacology

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Mid-gestational exposure to histone deacetylase inhibitor suberoylanilide hydroxamic acid influence cortical interneuron and astrocyte in mouse brain Nunung Yuniarti; Berry Juliandi; Tsukasa Sanosaka; Kinichi Nakashima
Indonesian Journal of Biotechnology Vol 22, No 1 (2017)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (835.413 KB) | DOI: 10.22146/ijbiotech.25986

Abstract

Suberoylanilide hydroxamic acid (SAHA) has been reported preclinically to diffuse across the placenta and to be found in fetal plasma, suggesting that it can influence the fetus if taken by a pregnant cancer patient. In utero exposure of SAHA to mouse embryos during mid-gestation was found to perturb corticogenesis. However, the influence of in utero administration of SAHA to mouse embryos during mid-gestation on astrocyte, glial cell, and inhibitory neurons (interneurons) is yet to be reported. Pregnant dams were divided into control and SAHA groups and given methyl cellulose (as control) and SAHA orally once a day for 3 days during mid-gestation, starting from embryonic day (E)12 until E14. Astrocyte, interneuron, and behavior analyses were performed on the pups from postnatal day 7 until adulthood (3 months old). Brains were harvested and immunohistochemistry, Western Blot, and RT-PCR were performed on their cortex area. Transient exposure of SAHA to mouse embryos resulted in a decrease and increase in cortical astrocyte and interneuron, respectively. Meanwhile, adult SAHA mice displayed significantly increased anxiety, decreased memory, altered long-term cognitive functions, and reduced social interactions. Our study suggests that exposure to SAHA during prominent neurogenic periods might imbalance the normal excitatory:inhibitory neuron ratio required for the precise regulation of physiological functions in the brain.
Exposure of Histone Deacetylase-2 Inhibitor Curcumin and Its Analogues in Self-Nano Emulsifying Drug Delivery System Change Memory and Cognitive Function, Anxiety, and Social Interaction Behavior in Mouse Nunung Yuniarti; Febri Wulandari; Ulfah Laily Azizah; Yance Anas; Retno Murwanti
Jurnal Farmasi Sains dan Komunitas (Journal of Pharmaceutical Sciences and Community) Vol 21, No 2 (2024)
Publisher : Sanata Dharma University

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.24071/jpsc.009660

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Class 1 and 2 histone deacetylase inhibitors (HDACI) have been reported as novel therapeutic approaches to treat neurodegenerative disorders, depression, anxiety, and cognitive deficits. HDACI ameliorated deficits in cognition and stress-related behaviors in a wide range of neurologic and psychiatric disorders. Preclinically, behavioral bioassay can be used to predict the influence of new compounds for treatment of these illnesses. Curcumin and its new analogues PGV-0 and PGV-1 have been reported to inhibit HDAC2. However, reports regarding the effect of curcumin and its analogues on memory and cognitive function, anxiety, and social interaction behavior are as yet to be examined. Mice were divided into control and treated groups. Brain disorder was induced by oral administration of 10% ethanol in sodium-CMC for 7 days. Curcumin, PGV-0, PGV-1, and sodium butyrate (as positive control) were then given orally once a day for 21 days. The behavior tests of social interaction, open field, radial 8-arm-maze, and passive avoidance were performed on day 29. To increase dissolution and bioavailability of the compounds, they were formulated in a self-nano emulsifying drug delivery system (SNEDDS). Brains were isolated and analyzed using PCR to investigate the expression of genes related to neurobehavioral disorders hdac2, trkB, and bdnf. In different doses, curcumin, PGV-0, and PGV-1 increased social interaction capability, declined anxiety level, and improved long-term memory and cognitive function. The mechanism proposed is: HDACI curcumin and its analogues (PGV-0 and PGV-1) that keep the histone protein in acetylation state increase bdnf expression. The increased trkB expression is increasing the activation of the bdnf gene because trkB is the primary receptor of bdnf that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. Thus, those mechanisms could improve long-term memory and cognitive function, increase social interaction, and reduce anxiety in ethanol-induced mice with brain disorders.
Co-Authors Berry Juliandi Febri Wulandari Kinichi Nakashima Retno Murwanti Tsukasa Sanosaka Ulfah Laily Azizah Yance Anas