Astrocyte dysfunction alters GABAergic communication and ammonia metabolism in the streptozotocin-induced sporadic Alzheimer's disease model

Journal of Alzheimer s Disease Reports, Journal Year: 2024, Volume and Issue: 8(1), P. 1381 - 1393

Published: March 1, 2024

Background In the sporadic model of Alzheimer's disease (AD), induced by intracerebroventricular streptozotocin (STZ) administration, cognitive impairment is accompanied specific astrocytic changes in hippocampus prior to amyloid deposition. Objective Hypothesizing that synthesis GABA, via MAO-B, contributes ammonia elevation, thereby compromising antioxidant defense and ATP synthesis, possibly contributing damage, we determined hippocampal levels glutamine synthetase (GS), monoamine oxidase B (MAO-B) other enzymes related GABA metabolism. Methods Immunoblotting RT-PCR assays were carried out samples Wistar rats, at 4 16 weeks post-STZ, STZ-induced AD model, corresponding pre-amyloid phases, respectively. Results We observed a reduction GS activity increased MAO-B content, both weeks, reinforcing idea astroglial dysfunction precedes phase. These alterations an increase content ornithine decarboxylase 1 (ODC1), which catalyzes putrescine (substrate for MAO-B), gene expression arginine-glycine amidinotransferase (AGAT), enzyme involved creatine, generation agonists. only seen phase model. Conclusions Our findings contribute explain greater damage occurs energy metabolism this stage, addition GABAergic loss. The reinforce importance STZ further our understanding phases.

Language: Английский

Apolipoprotein (APOA1, APOE, CLU) genes expression in the CA3 region of the hippocampus in an ischemic model of Alzheimer's disease with survival up to 2 years

Journal of Alzheimer s Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 16, 2024

Changes in the Alzheimer's disease-related apolipoprotein genes expression, occurring parallel with brain ischemia-induced neurodegeneration hippocampal CA3 area, may be crucial for development of memory loss and dementia.

Language: Английский

Alterations in the <em>amyloid protein precursor</em>, <em>α-secretase</em>, <em>β-secretase</em>, <em>presenilins</em> and <em>tau protein</em> Genes in the CA3 Area of the Hippocampus in a 2-Year Ischemic Model of Alzheimer’s Disease

Published: Sept. 30, 2023

Understanding the phenomena underlying non-selective susceptibility to ischemia of py-ramidal neurons in CA3 area hippocampus is important from point view elu-cidating mechanisms memory loss and development post-ischemic dementia. We used an ischemic model Alzheimer's disease study changes amyloid protein precursor gene expression, its cleavage enzymes tau af-ter a 10-minute brain with 12, 18, 24-month survival. Quantitative reverse tran-scriptase PCR assay showed that expression all genes contribute pro-duction was dysregulated within 2 years after ischemia. The above control values at times study. &alpha;-secretase also exceeded throughout In contrast, &beta;-secretase reaching maximum increase 12 months ischemia, below 18 again 24 Presenilin 1 significantly elevated follow-up period, peak both occurring This suggests studied are involved non-amyloidogenic processing precursor. Also, observation present is-chemia. Data indicate episode long-term survival causes damage death pyramidal manner dependent on modified protein. Thus defining new mechanism neuronal addition modification is-chemia useful identifying disease.

Language: Английский