Short-term dietary restriction maintains synaptic plasticity whereas short-term overfeeding alters cellular dynamics in the aged brain: evidence from the zebrafish model organism

• Published in: Neurobiology of aging Vol. 106; pp. 169 - 182
• Main Authors: Karoglu-Eravsar, Elif Tugce, Tuz-Sasik, Melek Umay, Adams, Michelle M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2021
• Subjects: Aging; Aging - pathology; Aging - physiology; Animals; Brain - cytology; Brain - pathology; Cognitive Dysfunction - etiology; Cognitive Dysfunction - prevention & control; Diet Therapy; Dietary restriction; Disks Large Homolog 4 Protein - metabolism; Doublecortin-Like Kinases - metabolism; Energy Intake - physiology; Feeding Behavior - physiology; Healthy Aging; Hyperphagia - complications; Hyperphagia - physiopathology; Models, Animal; Neuronal Plasticity - physiology; Overfeeding; Receptors, AMPA - metabolism; Synapses; Time Factors; Zebrafish; Aging; Zebrafish; Dietary restriction; Overfeeding; Synapses
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2021.06.010

•Aging decreases excitatory, inhibitory, presynaptic and neuronal protein levels.•Increased synaptic protein levels with DR likely maintain synaptic plasticity.•OF leads to an alteration of neuronal dynamics in aged subjects. Increased caloric intake (OF) impairs quality of life causing comorbidities with other diseases and cognitive deficits, whereas dietary restriction (DR) increases healthspan by preventing age-related deteriorations. To understand the effects of these opposing dietary regimens on the cellular and synaptic dynamics during brain aging, the zebrafish model, which shows gradual aging like mammals, was utilized. Global changes in cellular and synaptic markers with respect to age and a 12 week dietary regimen of OF and DR demonstrated that aging reduces the levels of the glutamate receptor subunits, GLUR2/3, inhibitory synaptic clustering protein, GEP, synaptic vesicle protein, SYP, and early-differentiated neuronal marker, HuC. DR significantly elevates levels of glutamate receptor subunits, GLUR2/3, and NMDA clustering protein, PSD95, levels, while OF subtly increases the level of the neuronal protein, DCAMKL1. These data suggest that decreased caloric intake within the context of aging has more robust effects on synapses than cellular proteins, whereas OF alters cellular dynamics. Thus, patterns like these should be taken into account for possible translation to human subjects.