Chronic oral d-galactose intake provokes age-related changes in the rat prefrontal cortex
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2023
Authors
Martinović, JelenaZarić Kontić, Marina
Dragić, Milorad
Todorović, Ana
Guševac Stojanović, Ivana
Mitrović, Nataša
Grković, Ivana
Drakulić, Dunja R.
Article (Published version)
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D-galactose (d-gal) is broadly used in animal aging studies as its chronic administration mimics learning and memory impairments related to aging in humans. However, within the few studies that utilize chronic oral d-gal intake, none of them is focused on alteration in synaptic structure and function. We examined the effects of 6-weeks oral d-gal intake (200 mg/kg and 500 mg/kg, dissolved in tap water) on age-related changes, with emphasis on the prefrontal cortex (PFC) and hippocampus (HIP) of adult male Wistar rats. Memory assessment was followed by histological examination of the PFC and HIP (Nissl staining and Iba-1 immunostaining), while in crude synaptosomal fractions the state of oxidative stress and the expression of proteins involved in glutamatergic signaling was determined. Although applied dosages compromised memory, alterations such as impaired sensory-motor function and aberrant morphology were not detected. In the PFC, analysis of microglia revealed reduction of branchin...g pattern following d-gal intake, in parallel with increased oxidative damage of proteins, lipids and disturbed pro-oxidant antioxidant balance. These changes in the PFC were further accompanied with decreased levels of vesicular glutamate transporter 1, syntaxin-1 and NMDA receptor 2B subunit in both treated groups. Simultaneously, the increased hippocampal oxidative damage of lipids was detected. Results indicate successful provocation of age-related changes following oral d-gal intake, and suggest greater sensitivity of the PFC to d-gal treatment than HIP.
Keywords:
Age-related changes / Glutamatergic signaling / Hippocampus / Oral d-galactose / Prefrontal cortexSource:
Behavioural Brain Research, 2023, 436, 114072-Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200017 (University of Belgrade, Institute of Nuclear Sciences 'Vinča', Belgrade-Vinča) (RS-MESTD-inst-2020-200017)
DOI: 10.1016/j.bbr.2022.114072
ISSN: 0166-4328
PubMed: 36030906
Scopus: 2-s2.0-85139572177
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VinčaTY - JOUR AU - Martinović, Jelena AU - Zarić Kontić, Marina AU - Dragić, Milorad AU - Todorović, Ana AU - Guševac Stojanović, Ivana AU - Mitrović, Nataša AU - Grković, Ivana AU - Drakulić, Dunja R. PY - 2023 UR - https://vinar.vin.bg.ac.rs/handle/123456789/10461 AB - D-galactose (d-gal) is broadly used in animal aging studies as its chronic administration mimics learning and memory impairments related to aging in humans. However, within the few studies that utilize chronic oral d-gal intake, none of them is focused on alteration in synaptic structure and function. We examined the effects of 6-weeks oral d-gal intake (200 mg/kg and 500 mg/kg, dissolved in tap water) on age-related changes, with emphasis on the prefrontal cortex (PFC) and hippocampus (HIP) of adult male Wistar rats. Memory assessment was followed by histological examination of the PFC and HIP (Nissl staining and Iba-1 immunostaining), while in crude synaptosomal fractions the state of oxidative stress and the expression of proteins involved in glutamatergic signaling was determined. Although applied dosages compromised memory, alterations such as impaired sensory-motor function and aberrant morphology were not detected. In the PFC, analysis of microglia revealed reduction of branching pattern following d-gal intake, in parallel with increased oxidative damage of proteins, lipids and disturbed pro-oxidant antioxidant balance. These changes in the PFC were further accompanied with decreased levels of vesicular glutamate transporter 1, syntaxin-1 and NMDA receptor 2B subunit in both treated groups. Simultaneously, the increased hippocampal oxidative damage of lipids was detected. Results indicate successful provocation of age-related changes following oral d-gal intake, and suggest greater sensitivity of the PFC to d-gal treatment than HIP. T2 - Behavioural Brain Research T1 - Chronic oral d-galactose intake provokes age-related changes in the rat prefrontal cortex VL - 436 SP - 114072 DO - 10.1016/j.bbr.2022.114072 ER -
@article{ author = "Martinović, Jelena and Zarić Kontić, Marina and Dragić, Milorad and Todorović, Ana and Guševac Stojanović, Ivana and Mitrović, Nataša and Grković, Ivana and Drakulić, Dunja R.", year = "2023", abstract = "D-galactose (d-gal) is broadly used in animal aging studies as its chronic administration mimics learning and memory impairments related to aging in humans. However, within the few studies that utilize chronic oral d-gal intake, none of them is focused on alteration in synaptic structure and function. We examined the effects of 6-weeks oral d-gal intake (200 mg/kg and 500 mg/kg, dissolved in tap water) on age-related changes, with emphasis on the prefrontal cortex (PFC) and hippocampus (HIP) of adult male Wistar rats. Memory assessment was followed by histological examination of the PFC and HIP (Nissl staining and Iba-1 immunostaining), while in crude synaptosomal fractions the state of oxidative stress and the expression of proteins involved in glutamatergic signaling was determined. Although applied dosages compromised memory, alterations such as impaired sensory-motor function and aberrant morphology were not detected. In the PFC, analysis of microglia revealed reduction of branching pattern following d-gal intake, in parallel with increased oxidative damage of proteins, lipids and disturbed pro-oxidant antioxidant balance. These changes in the PFC were further accompanied with decreased levels of vesicular glutamate transporter 1, syntaxin-1 and NMDA receptor 2B subunit in both treated groups. Simultaneously, the increased hippocampal oxidative damage of lipids was detected. Results indicate successful provocation of age-related changes following oral d-gal intake, and suggest greater sensitivity of the PFC to d-gal treatment than HIP.", journal = "Behavioural Brain Research", title = "Chronic oral d-galactose intake provokes age-related changes in the rat prefrontal cortex", volume = "436", pages = "114072", doi = "10.1016/j.bbr.2022.114072" }
Martinović, J., Zarić Kontić, M., Dragić, M., Todorović, A., Guševac Stojanović, I., Mitrović, N., Grković, I.,& Drakulić, D. R.. (2023). Chronic oral d-galactose intake provokes age-related changes in the rat prefrontal cortex. in Behavioural Brain Research, 436, 114072. https://doi.org/10.1016/j.bbr.2022.114072
Martinović J, Zarić Kontić M, Dragić M, Todorović A, Guševac Stojanović I, Mitrović N, Grković I, Drakulić DR. Chronic oral d-galactose intake provokes age-related changes in the rat prefrontal cortex. in Behavioural Brain Research. 2023;436:114072. doi:10.1016/j.bbr.2022.114072 .
Martinović, Jelena, Zarić Kontić, Marina, Dragić, Milorad, Todorović, Ana, Guševac Stojanović, Ivana, Mitrović, Nataša, Grković, Ivana, Drakulić, Dunja R., "Chronic oral d-galactose intake provokes age-related changes in the rat prefrontal cortex" in Behavioural Brain Research, 436 (2023):114072, https://doi.org/10.1016/j.bbr.2022.114072 . .