Details

Autor(en) / Beteiligte

• de Souza, Débora Guerini
• da Rocha, Andreia Silva
• Almeida, Roberto Farina
• Peixoto, Guilherme G. Schu
• Salles, Giovanna Bortoluzzi
• Oliveira, Ana Cristina Laydner Joly
• Limberger, Christian
• de Bastiani, Marco Antônio
• Greggio, Samuel
• Venturin, Gianina Teribele
• da Costa, Jaderson Costa
• Souza, Diogo O.
• Zimmer, Eduardo R.

Titel

Inflammatory and metabolic responses in the aging rat brain

Ist Teil von

• Alzheimer's & dementia, 2023-12, Vol.19 (S24)

Erscheinungsjahr

2023

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Abstract Background The brain is an energetically demanding organ that mostly relies on glucose oxidation to sustain its sophisticated networks. Transcriptomic studies suggest metabolic‐related genes are downregulated in the aging brain but inflammation‐related genes are highly upregulated. Astrocytes are key mediators of brain inflammation and metabolism. Yet, the relationship between inflammatory signals and energy substrates consumption in the aging brain remains unclear. To address this question, we investigated the response of the young and aged rat brain metabolism to a nonsteroidal anti‐inflammatory (NSAID) drug. Method Five young adults (4 mo), and five aged (24 mo) male Wistar rats were scanned using positron emission microtomography with 18 F‐fluorodeoxyglucose ([ 18 F]FDG‐PET). Scans were done under basal conditions or after three‐day treatment with 5mg/kg ketoprofen (i.p.), an NSAID known to cross the blood‐brain barrier. Standard uptake values ratios (SUVr, pons as reference) were calculated for the main brain regions. Synaptosome and total mitochondria preparations from the cortex had their oxygen consumption rates measured in an Oroboros Instrument, using a SUIT protocol. Results were analyzed by t‐test, with statistical significance P < 0.05. Result Under basal conditions, glucose uptake showed no differences between young and aged rats. After ketoprofen treatment, clusters of glucose hypermetabolism appeared in the cortex and hippocampus of the adult but not the aged brain. Synaptosomal and mitochondrial preparations did not present differences in ATP‐linked, maximal, or leak respiration between groups under basal conditions. However, aged synaptosomes (t = 3.417, p = 0.0112) and total mitochondria (t = 3.131, p = 0.0166) presented higher respiratory coupling ratios. Conclusion We previously showed that [ 18 F]FDG‐PET signal highly depends on astrocyte function. The lack of response to ketoprofen in aged rats may be related to astrocyte dysfunction in aging. As a counter‐response to the aging process, the brain mitochondria are highly coupled, keeping the system as efficient as necessary. Our findings indicate that brain metabolism might not be coupled to inflammation in the aged rat brain. Still, we identified a remarkable plasticity of the mitochondria, which can sustain physiological responses despite the aging process.