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Your search keyword '"Hadi Mirzapourdelavar"' showing total 2 results
Start Over Author "Hadi Mirzapourdelavar" Topic aging
2 results on '"Hadi Mirzapourdelavar"'

1. Aging-Associated Changes in Cognition, Expression and Epigenetic Regulation of Chondroitin 6-Sulfotransferase Chst3

Author

David Baidoe-Ansah, Sadman Sakib, Shaobo Jia, Hadi Mirzapourdelavar, Luisa Strackeljan, Andre Fischer, Stepan Aleshin, Rahul Kaushik, and Alexander Dityatev

Subjects
aging, cognitive decline, extracellular matrix, carbohydrate sulfotransferase 3, 6-sulfation, epigenetic regulation, Cytology, QH573-671
Abstract

Understanding changes in the expression of genes involved in regulating various components of the neural extracellular matrix (ECM) during aging can provide an insight into aging-associated decline in synaptic and cognitive functions. Hence, in this study, we compared the expression levels of ECM-related genes in the hippocampus of young, aged and very aged mice. ECM gene expression was downregulated, despite the accumulation of ECM proteoglycans during aging. The most robustly downregulated gene was carbohydrate sulfotransferase 3 (Chst3), the enzyme responsible for the chondroitin 6-sulfation (C6S) of proteoglycans. Further analysis of epigenetic mechanisms revealed a decrease in H3K4me3, three methyl groups at the lysine 4 on the histone H3 proteins, associated with the promoter region of the Chst3 gene, resulting in the downregulation of Chst3 expression in non-neuronal cells. Cluster analysis revealed that the expression of lecticans—substrates of CHST3—is tightly co-regulated with this enzyme. These changes in ECM-related genes were accompanied by an age-confounded decline in cognitive performance. Despite the co-directional impairment in cognitive function and average Chst3 expression in the studied age groups, at the individual level we found a negative correlation between mRNA levels of Chst3 and cognitive performance within the very aged group. An analysis of correlations between the expression of ECM-related genes and cognitive performance in novel object versus novel location recognition tasks revealed an apparent trade-off in the positive gene effects in one task at the expense of another. Further analysis revealed that, despite the reduction in the Chst3 mRNA, the expression of CHST3 protein is increased in glial cells but not in neurons, which, however, does not lead to changes in the absolute level of C6S and even results in the decrease in C6S in perineuronal, perisynaptic and periaxonal ECM relative to the elevated expression of its protein carrier versican.

Published
2022
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2. Overexpression of protein kinase Mζ in the hippocampal dentate gyrus rescues amyloid-β-induced synaptic dysfunction within entorhinal-hippocampal circuit

Author

Hadi Mirzapourdelavar, Niloufar Amini, Shayan Aliakbari, Hamid Gholami Pourbadie, Mohammad Sayyah, and Naser Naghdi

Subjects
Male, 0301 basic medicine, Aging, Amyloid beta, Long-Term Potentiation, Gene Expression, Neurotransmission, Hippocampal formation, Hippocampus, Synaptic Transmission, 03 medical and health sciences, 0302 clinical medicine, Memory, Animals, Entorhinal Cortex, Humans, Molecular Targeted Therapy, Rats, Wistar, Protein kinase A, Protein Kinase C, Memory Disorders, Amyloid beta-Peptides, biology, Chemistry, General Neuroscience, Dentate gyrus, Long-term potentiation, Entorhinal cortex, HEK293 Cells, 030104 developmental biology, Dentate Gyrus, Synapses, Synaptic plasticity, biology.protein, Neurology (clinical), Geriatrics and Gerontology, Neuroscience, 030217 neurology & neurosurgery, Developmental Biology
Abstract

Entorhinal cortex (EC) is one of the first cerebral regions affected in the early phase of Alzheimer's disease (AD). Soluble forms of amyloid beta (Aβ) impair synaptic transmission in experimental AD models. Protein kinase Mζ (PKMζ) is an atypical persistently active protein kinase C, known to maintain long term synaptic plasticity and memory, but its role in AD has not yet been described. We examined effect of PKMζ overexpression on the late long-term potentiation (L-LTP) in the dentate gyrus (DG) following EC amyloidopathy. Oligomeric Aβ 1-42 (oAβ) or vehicle was bilaterally microinjected into the EC of the male Wistar rats. After 1 week, 2 µL of lentiviral vector (~108 TU/mL) encoding PKMζ genome was injected into the DG. One week later, synaptic responses and the LTP persistence were assessed in DG of freely moving animals during 90 minutes to 7 days period. Novel object recognition, passive avoidance and spatial memories were also tested. In rats with EC amyloidopathy, LTP was induced with less amplitude compared to the control group, and extinguished after 24 h. PKMζ overexpression in DG augmented synaptic responses (PS-LTP amplitudes) and maintained LTP over 1 week. PKMζ ameliorated recognition and memory deficits in rats with EC amyloidopathy. Microinjection of PKMζ inhibitor, zeta inhibitory peptide, into the DG abolished the boosting effect of PKMζ on synaptic activity and memory performance. PKMζ-dependent pathway could be a potential therapeutic target to combat synaptic failure and memory deficit in the early phase of AD.

Published
2021
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