title: Ketogenic diets cause opposing changes in synaptic morphology in CA1 hippocampus and dentate gyrus of late-adult rats.
abstract: Ketogenic diets (KDs) have beneficial effects on several diseases, such as epilepsy, mitochondriopathies, cancer, and neurodegeneration. However, little is known about their effects on aging individuals. In the present study, late-adult (19-month-old) rats were fed for 8 weeks with two medium chain triglycerides (MCT)-KDs, and the following morphologic parameters reflecting synaptic plasticity were evaluated in stratum moleculare of hippocampal CA1 region (SM CA1) and outer molecular layer of hippocampal dentate gyrus (OML DG): average area (S), numeric density (Nv(s)), and surface density (Sv) of synapses, and average volume (V), numeric density (Nv(m)), and volume density (Vv) of synaptic mitochondria. In SM CA1, MCT-KDs induced the early appearance of the morphologic patterns typical of old animals (higher S and V, and lower Nv(s) and Nv(m)). On the contrary, in OML DG, Sv and Vv of MCT-KDs-fed rats were higher (as a result of higher Nv(s) and Nv(m)) versus controls; these modifications are known to improve synaptic function and metabolic supply. The opposite effects of MCT-KDs might reflect the different susceptibility to aging processes: OML DG is less vulnerable than SM CA1, and the reactivation of ketone bodies uptake and catabolism might occur more efficiently in this region, allowing the exploitation of their peculiar metabolic properties. Present findings provide the first evidence that MCT-KDs may cause opposite morphologic modifications, being potentially harmful for SM CA1 and potentially advantageous for OML DG. This implies risks but also promising potentialities for their therapeutic use during aging.
authors.affiliation: Neurobiology of Aging Laboratory, INRCA Research Department, Ancona, Italy. m.balietti@inrca.it
authors.forename: Marta
authors.initials: M
authors.lastname: Balietti
authors.forename: Belinda
authors.initials: B
authors.lastname: Giorgetti
authors.forename: Patrizia
authors.initials: P
authors.lastname: Fattoretti
authors.forename: Yessica
authors.initials: Y
authors.lastname: Grossi
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Di Stefano
authors.forename: Tiziana
authors.initials: T
authors.lastname: Casoli
authors.forename: Daniela
authors.initials: D
authors.lastname: Platano
authors.forename: Moreno
authors.initials: M
authors.lastname: Solazzi
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Orlando
authors.forename: Giorgio
authors.initials: G
authors.lastname: Aicardi
authors.forename: Carlo
authors.initials: C
authors.lastname: Bertoni-Freddari
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000375:Aging / Q000473:pathology*; D000818:Animals; D001835:Body Weight; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D018891:Dentate Gyrus / Q000473:pathology*; D050528:Diet, Carbohydrate-Restricted; D004435:Eating; D006624:Hippocampus / Q000473:pathology*; D007657:Ketone Bodies / Q000096:biosynthesis*; D008099:Liver / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000648:ultrastructure*; D014280:Triglycerides / Q000096:biosynthesis
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D007657:Ketone Bodies; D014280:Triglycerides; D020155:3-Hydroxybutyric Acid