BACKGROUND: Different evidence suggests that ketogenic diet (KD) ameliorates neurological disfunctions including core symptoms of autism spectrum disorders (ASD). In view of this, we have hypothesized that KD may induce a positive effect even on some ASD comorbidities, such as motor impairment and anxiety, along with cerebellar inflammation and axonal demyelination. METHODS: BTBR T+ Itpr3tf/J (BTBR) and C57BL/6 (C57) mice were fed with a standard chow diet (CD) or KD for 5 weeks. Modified Beam Walking (MBW) and Open Field (OFT) tests were used to examine locomotor activity and anxiety-related behaviors. At the same time, cerebellar pro-inflammatory cytokines TNF-α, IL-1β and IL-6 were evaluated together with g-ratio of myelinated axons, detected by TEM. The levels of different isoforms of the myelin basic protein (21.5, 18.5/17- and 14 kDa MBP) were also analyzed. RESULTS: As expected, KD improved motor deficits and anxiety in BTBR mice as displayed by significant increases (p<0.001) in the number of peeking and laps during MBW test rather than BTBR treated with CD. Furthermore, reduced path speed and enhanced path length (p<0.001) in OFT were reported for the same KD-fed mice strain. Contextually, some pro-inflammatory cytokines (TNF-α and IL-1β) were significantly (p<0.05) reduced in the cerebellum of BTBRs exposed to KD. Such ameliorations were correlated to a reduction of g-ratio (p<0.001), together with an upregulation (p<0.05) of the MBP isoform 18.5/17-kDa. CONCLUSIONS: Overall, these findings support a promyelinating and anti-inflammatory action of KD, which very likely determined mitigation of motor disorder and anxiety-like behaviors.
Alò et al. (Fri,) studied this question.