Ketogenic diet restores aberrant cortical motor maps and excitation-to-inhibition imbalance in the BTBR mouse model of autism spectrum disorder

Smith, Jacklyn D.; Rho, Jong M.; Teskey, G. Campbell

doi:10.1016/j.bbr.2016.02.015

Cited by 30 publications

(15 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This balance governs the memory, learning, attention, intelligence, and thinking, involving the dominant aspects of cognitive function. Excitation/inhibition imbalance was demonstrated to related with a variety of disorders, such as drug abuse ( den Boon et al, 2015 ), autism spectrum disorder ( Dickinson et al, 2016 ; Smith et al, 2016 ), Alzheimer’s disease ( Povysheva and Johnson, 2016 ), schizophrenia ( Lisman, 2012 ), Down syndrome ( Souchet et al, 2014 ), epileptic syndromes ( Petroff et al, 1996 ), Tourette’s syndrome ( Singer and Minzer, 2003 ), certified by the pharmacological, transgenic, and electrophysiological technology in these articles. And existing studies have been concentrated at the brain regions, involving the PFC, hippocampus, cerebellum, and occipital lobe ( Petroff et al, 1996 ; Lisman, 2012 ; Souchet et al, 2014 ; den Boon et al, 2015 ; Povysheva and Johnson, 2016 ; Krystal et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Traumatic Stress Produces Distinct Activations of GABAergic and Glutamatergic Neurons in Amygdala

Fang

Huang

et al. 2018

Front. Neurosci.

View full text Add to dashboard Cite

Posttraumatic stress disorder (PTSD) is an anxiety disorder characterized by intrusive recollections of a severe traumatic event and hyperarousal following exposure to the event. Human and animal studies have shown that the change of amygdala activity after traumatic stress may contribute to occurrences of some symptoms or behaviors of the patients or animals with PTSD. However, it is still unknown how the neuronal activation of different sub-regions in amygdala changes during the development of PTSD. In the present study, we used single prolonged stress (SPS) procedure to obtain the animal model of PTSD, and found that 1 day after SPS, there were normal anxiety behavior and extinction of fear memory in rats which were accompanied by a reduced proportion of activated glutamatergic neurons and increased proportion of activated GABAergic neurons in basolateral amygdala (BLA). About 10 days after SPS, we observed enhanced anxiety and impaired extinction of fear memory with increased activated both glutamatergic and GABAergic neurons in BLA and increased activated GABAergic neurons in central amygdala (CeA). These results indicate that during early and late phase after traumatic stress, distinct patterns of activation of glutamatergic neurons and GABAergic neurons are displayed in amygdala, which may be implicated in the development of PTSD.

show abstract

Section: Discussionmentioning

confidence: 99%

Traumatic Stress Produces Distinct Activations of GABAergic and Glutamatergic Neurons in Amygdala

Fang

Huang

et al. 2018

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…In the gestational valproic acid model, KD treatment normalized dysfunctions in mitochondrial respiration [ 27 ]; mitochondrial dysfunction is common is ASD [ 56 – 58 ]. In the BTBR strain model, KD treatment normalized abnormal cerebrocortical excitation/inhibition [ 59 ], a clinically-relevant aspect of ASD [ 60 ]. KD treatment enhanced social novelty-induced neuronal activation in several brain areas of Engrailed 2 knockout mice–but did not normalize levels of monoamine neurotransmitters [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder

et al. 2017

View full text Add to dashboard Cite

Prenatal factors influence autism spectrum disorder (ASD) incidence in children and can increase ASD symptoms in offspring of animal models. These may include maternal immune activation (MIA) due to viral or bacterial infection during the first trimesters. Unfortunately, regardless of ASD etiology, existing drugs are poorly effective against core symptoms. For nearly a century a ketogenic diet (KD) has been used to treat seizures, and recent insights into mechanisms of ASD and a growing recognition that immune/inflammatory conditions exacerbate ASD risk has increased interest in KD as a treatment for ASD. Here we studied the effects of KD on core ASD symptoms in offspring exposed to MIA. To produce MIA, pregnant C57Bl/6 mice were injected with the viral mimic polyinosinic-polycytidylic acid; after weaning offspring were fed KD or control diet for three weeks. Consistent with an ASD phenotype of a higher incidence in males, control diet-fed MIA male offspring were not social and exhibited high levels of repetitive self-directed behaviors; female offspring were unaffected. However, KD feeding partially or completely reversed all MIA-induced behavioral abnormalities in males; it had no effect on behavior in females. KD-induced metabolic changes of reduced blood glucose and elevated blood ketones were quantified in offspring of both sexes. Prior work from our laboratory and others demonstrate KDs improve relevant behaviors in several ASD models, and here we demonstrate clear benefits of KD in the MIA model of ASD. Together these studies suggest a broad utility for metabolic therapy in improving core ASD symptoms, and support further research to develop and apply ketogenic and/or metabolic strategies in patients with ASD.

show abstract

“…The changes, or lack thereof, may reflect cell-intrinsic epigenetic or genetic programming, or other factors in the peripheral immune environment may also be necessary to produce neuro-immune alterations in behavior. Importantly, the characteristic low sociability in BTBR mice are hypothesized to emerge from a combination of changes in nervous system (Fenlon et al, 2015), gastrointestinal-microbiota (Klein et al, 2016), metabolic (Smith et al, 2016; Zilkha et al, 2016), and immunological function (Careaga et al, 2015b; Onore et al, 2013). This suggests there may be several factors working synergistically to modulate the social behavior improvements observed in BTBR-Allogeneic recipients and underscores the complex nature of social behavior deficits in the BTBR mouse strain.…”

Section: Discussionmentioning

confidence: 99%

C57BL/6J bone marrow transplant increases sociability in BTBR T+ Itpr3tf/J mice

Schwartzer

Onore

Rose

et al. 2017

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

Associative studies across a range of neurodevelopmental disorders have revealed a relationship between immune system function and behavioral deficits. These correlations are particularly evident in individuals with autism spectrum disorders (ASD), a developmental disorder characterized by social behavior deficits and noted for its high instances of immune system dysfunction. Mouse models provide a unique opportunity to explore causal links between immune and nervous system function and reveal how changes in these systems alter behavioral profiles. The BTBR T+ Itpr3tf/J (BTBR) mouse strain is characterized by both social behavior impairments and aberrant immune responses, affording the unique opportunity to investigate the causal relationship between behavior and immunity through direct manipulation of these systems. Using bone marrow from the highly social C57BL/6J (C57) mouse strain, BTBR mice were tested for changes in social approach behavior and repetitive grooming following irradiation and bone marrow transplant. BTBR recipient mice treated with allogeneic bone marrow from C57 donor mice, but not syngeneic BTBR bone marrow, displayed increased sociability as measured by the three-chamber social approach task and total time spent social sniffing. In addition, C57 recipient mice given allogeneic bone marrow from BTBR donors showed a significant increase in repetitive grooming behavior. These data provide evidence for a causal relationship between peripheral immune phenotype and social behavior in the BTBR mouse strain and further strengthen and expand on our existing understanding of the role of immune function in behavior.

show abstract

Ketogenic diet restores aberrant cortical motor maps and excitation-to-inhibition imbalance in the BTBR mouse model of autism spectrum disorder

Cited by 30 publications

References 18 publications

Traumatic Stress Produces Distinct Activations of GABAergic and Glutamatergic Neurons in Amygdala

Traumatic Stress Produces Distinct Activations of GABAergic and Glutamatergic Neurons in Amygdala

Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder

C57BL/6J bone marrow transplant increases sociability in BTBR T+ Itpr3tf/J mice

Contact Info

Product

Resources

About