Article 2025 · 0 atıf

Neuroprotective and Cognitive Benefits of a Ketogenic Diet in a Type 2 Diabetes Rat Model

Tamer, Sevil Arabaci, Doganay, Songul, Kose, Fadime, Bolat, Ismail, Ahmed, Nawar Imad Ahmed

Özet

Diabetes mellitus is a widespread metabolic disease that also increases the risk of cognitive decline through mechanisms such as oxidative stress, inflammation, and vascular damage. Recently, the ketogenic diet has attracted attention as a nutritional approach that may improve glucose control and support cognitive health in diabetes. The present study evaluated the neuroprotective and behavioral effects of a ketogenic diet (KD) in a rat model of type 2 diabetes mellitus (T2DM). Adult male Wistar rats were assigned to four groups (n = 7 each): control (normal diet), KD, diabetic (high-fat diet + nicotinamide (60 mg/kg, ip) / streptozotocin (50 mg/kg, i.p)), and diabetic + KD. After eight weeks, we assessed anxiety-like and memory behaviors via the hole-board, elevated plus maze, and object recognition tests. Oxidative stress markers (malondialdehyde, MDA; glutathione, GSH) and neuroinflammatory mediators (S100 beta, TNF-alpha, IL-6) were quantified. Histopathological and immunohistochemical analyses of CA1, CA3, and dentate gyrus regions evaluated neuronal integrity and oxidative DNA damage (8-OHdG) and neurotrophic factor BDNF. KD alone induced ketosis and modest anxiety-like behaviors but preserved recognition memory. In diabetic rats, KD significantly reduced hyperglycemia and insulin (p < 0.001-0.01), ameliorated oxidative damage (p < 0.01), and partially normalized S100 beta, TNF-alpha, IL-6, and BDNF levels (p < 0.05). Behaviorally, KD attenuated diabetes-induced anxiety and improved cognitive difference score (p < 0.05). Histologically, KD mitigated diabetes-associated neuronal degeneration and reduced 8-OHdG immunopositivity. These findings indicate that KD confers neuroprotective benefits under diabetic conditions by modulating glycemic control, oxidative stress, inflammation, and neurotrophic support in the brain.

Anahtar Kelimeler

Ketogenic diet Type 2 diabetes mellitus Neuroinflammation Oxidative stress Behavioral outcomes NEUROTROPHIC FACTOR INFLAMMATORY CYTOKINES BETA-HYDROXYBUTYRATE INSULIN-RESISTANCE OXIDATIVE STRESS KETONE-BODIES HIPPOCAMPUS DYSFUNCTION IMPAIRMENT EXPRESSION

WoS Kategorileri

Neurosciences

Sürdürülebilir Kalkınma Amaçları

Sağlık ve Kaliteli Yaşam

Künye

Dergi: MOLECULAR NEUROBIOLOGY
Yıl: 2025
Cilt: 63
Sayı: 1
ISSN: 0893-7648
eISSN: 1559-1182
DOI: 10.1007/s12035-025-05328-z
WoS UID: WOS:001627883700012

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