1. Abhishek M, Rubal S, Rohit K, Rupa J, Phulen S, Gurjeet K, Raj SA, Manisha P, Alka B, Ramprasad P, Bikash M. Neuroprotective effect of the standardised extract of Bacopa monnieri (BacoMind) in valproic acid model of autism spectrum disorder in rats. J Ethnopharmacol;2022 (Jul 15);293:115199.

ETHNOPHARMACOLOGICAL RELEVANCE: Bacopa monnieri (BM) is commonly employed in the Indian traditional system of medicines, i.e. Ayurveda as a memory booster, antioxidant, anti-inflammatory, antipyretic, analgesic, sedative and anti-epileptic for decades. AIM OF THE STUDY: To evaluate the neuroprotective effect of Bacopa monnieri (BM) in experimental model of autism spectrum disorder (ASD) in Wistar rats and explore its mechanism of action. MATERIALS AND METHODS: BacoMind, was evaluated for its neuroprotective effect in valproic acid (VPA) model of ASD. For in-vivo study, the pregnant female Wistar rats were divided in two groups; normal control (NC) and VPA group who received single dose of normal saline (0.9%) or 600 mg/kg dose of VPA respectively on gestation day (G.D) 12.5. After the birth, all pups were segregated according to the sex. All the male pups from the dams were divided into six groups: Group 1 (NC, treated with only 0.9% normal saline, group 2 (VPA, treated 600 mg/kg on G.D12.5 and normal saline from post natal day (PND) 23 to 43), group 3 (risperidone 2.5 mg/kg, PND 23 to 43) and groups 4, 5 and 6 (BM 20, 40, 80 mg/kg, PND 23 to 43). All experimental groups were subjected to batteries of behavior parameters (three chamber sociability test, Morris Water Maze, elevated plus maze, open field and rota rod test), biochemical parameters such as oxidative stress (GSH, SOD, Catalase, MDA), inflammatory cytokines (Il-1β, IL-6, IL-10, TNF-α), histopathological examination (cresyl violet staining) of hippocampus (HC) and prefrontal cortex (PFC) regions. Further, the mRNA as well as protein expression of AMPA receptor was evaluated using RT-PCR and western blot respectively to study the mechanism of neuroprotective effect of BM. The in-silico analysis followed evaluating the binding profile of different constituents of BacoMind with AMPA receptor. RESULTS: The results of the in-vivo study indicated BM at 80 mg/kg ameliorated abnormal behavioral paradigms such as social deficits, repetitive behavior, learning and memory impairments, and motor coordination exhibited by the VPA model of ASD in rats. Furthermore, BM was found to have a significant anti-oxidant (increasing GSH, SOD, and catalase and decreasing MDA levels) and anti-inflammatory properties (decreasing IL-1β, 6, TNF- α). The histopathological score was also found to be significantly improved by BM in a dose dependent manner in both HC and PFC. In addition to this, the up-regulated mRNA as well as protein expression of AMPA receptor was significantly reduced by 80 mg/kg dose of BM in both HC and PFC. Further, the in-silico analysis of different constituents of BacoMind with AMPA receptor demonstrated that luteolin and apigenin showed good binding to both the competitive antagonist binding site, non-competitive antagonist binding site and allosteric modulator site while Bacosaponin C showed good binding to the non-competitive antagonist binding site. CONCLUSION: The present study concluded that BM can be a potential candidate for ameliorating the ASD symptoms in rats and acts via modulating the up-regulated AMPA receptor expression.

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2. Alpay M, Yucel F. Changes of Cerebellar Cortex in a Valproic Acid-Induced Rat Model of Autism. Int J Dev Neurosci;2022 (Jul 13)

In this study, 32 male Sprague-Dawley rats (8 for each group) were used in total to examine the effects of valproic acid on rat cerebellum. It was determined that the experimental group received valproic acid (600mg/kg) on embryonic day 15 and postnatal day 11, whereas the control group was treated with saline on the same days. Moreover, on the postnatal 30(th) day, the cerebellums of all pups were removed and prepared for light and electron microscopy. The numerical density of granule cells in the cerebellum of experimental groups of rats increased whereas the numerical density of Purkinje cells decreased. Furthermore, the granule cells had a smaller mean nuclear diameter in one of the experimental groups while the Purkinje cells had in both experimental groups than those in the comparison group. Thus, the numerical density of synaptic discs and their mean diameter in the cerebellar granular layer of experimental groups were significantly decreased compared to the corresponding controls; also, the synapse-to-neurons ratio, a parameter indicating interneural connectivity, was the same. Consequently, it was seen that valproic acid administration to pups in prenatal or early postnatal days causes changes in number of neurons and synapses in the cerebellum of rats.

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3. Butera CD, Harrison L, Kilroy E, Jayashankar A, Shipkova M, Pruyser A, Aziz-Zadeh L. Relationships between alexithymia, interoception, and emotional empathy in autism spectrum disorder. Autism;2022 (Jul 14):13623613221111310.

Empathy, the ability to understand and share the emotions of others, is a necessary skill for social functioning and can be categorized into cognitive and emotional empathy. There is evidence to suggest that individuals with autism spectrum disorder have difficulties with cognitive empathy, the ability to imagine how another person is thinking or feeling. However, it is unclear if individuals with autism spectrum disorder struggle with emotional empathy, the ability to share and feel emotions others are experiencing. Self-report and interview data were collected to explore the relationships between interoception (individuals’ self-reported awareness of sensation from their body such as thirst, heartbeat, etc.), alexithymia (an individual’s ability to describe and distinguish between their own emotions), and emotional empathy in 35 youth with autism spectrum disorder and 40 typically developing youth. Greater personal distress to others’ emotions and greater difficulty describing and recognizing self-emotions were associated with reporting fewer physical sensations in the body when experiencing emotion in the autism spectrum disorder group. The results of this study suggest that while autism spectrum disorder youth with concomitant alexithymia may experience emotional empathy differently, it should not be characterized as an absence of a capacity for emotional empathy.

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4. Chavez AE, Feldman MS, Carter AS, Eisenhower A, Mackie TI, Ramella L, Hoch N, Sheldrick RC. Delays in autism diagnosis for U.S. Spanish-speaking families: The contribution of appointment availability. Evid Based Pract Child Adolesc Ment Health;2022;7(2):275-293.

Promoting equity in health services requires an understanding of the mechanisms that produce disparities. Utilizing a sequential, mixed-methods, explanatory study design, we analyzed child-, family-, and organizational-level factors and their association with wait times for an ASD diagnostic evaluation among 353 families scheduled for English and Spanish language appointments (27% Spanish language). A subset of parents and caregivers participated in English and Spanish language focus groups to provide their perspectives on the diagnostic process. Spanish language was associated with greater completion of, and time to evaluations than English language. The only variable found to mediate associations with time-to-evaluation was appointment availability – an organizational factor. Qualitative results elucidate potential explanations for greater Spanish language evaluation completion (e.g., fewer community-based diagnostic options). Results serve as a case study to support the utility and importance of analyzing the influence of organizational-level factors on delays and disparities for childhood health and mental health services. We discuss our findings in relation to strategies that can be widely applied to support equitable services access for childhood diagnostic and intervention services.

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5. Huo Y, Lu W, Tian Y, Hou Q, Man HY. Prkn knockout mice show autistic-like behaviors and aberrant synapse formation. iScience;2022 (Jul 15);25(7):104573.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with high genetic heterogeneity, affecting one in 44 children in the United States. Recent genomic sequencing studies from autistic human individuals indicate that PARK2, a gene that has long been considered in the pathogenesis of Parkinson’s disease, is involved in ASD. Here, we report that Prkn knockout (KO) mice demonstrate autistic-like behaviors including impaired social interaction, elevated repetitive behaviors, and deficits in communication. In addition, Prkn KO mice show reduced neuronal activity in the context of sociability in the prelimbic cortex. Cell morphological examination of layer 5 prelimbic cortical neurons shows a reduction in dendritic arborization and spine number. Furthermore, biochemistry and immunocytochemistry analyses reveal alterations in synapse density and the molecular composition of synapses. These findings indicate that Prkn is implicated in brain development and suggest the potential use of the Prkn KO mouse as a model for autism research.

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6. Kim IB, Lee T, Lee J, Kim J, Lee S, Koh IG, Kim JH, An JY, Lee H, Kim WK, Ju YS, Cho Y, Yu SJ, Kim SA, Oh M, Han DW, Kim E, Choi JK, Yoo HJ, Lee JH. Non-coding de novo mutations in chromatin interactions are implicated in autism spectrum disorder. Mol Psychiatry;2022 (Jul 15)

Three-dimensional chromatin interactions regulate gene expressions. The significance of de novo mutations (DNMs) in chromatin interactions remains poorly understood for autism spectrum disorder (ASD). We generated 813 whole-genome sequences from 242 Korean simplex families to detect DNMs, and identified target genes which were putatively affected by non-coding DNMs in chromatin interactions. Non-coding DNMs in chromatin interactions were significantly involved in transcriptional dysregulations related to ASD risk. Correspondingly, target genes showed spatiotemporal expressions relevant to ASD in developing brains and enrichment in biological pathways implicated in ASD, such as histone modification. Regarding clinical features of ASD, non-coding DNMs in chromatin interactions particularly contributed to low intelligence quotient levels in ASD probands. We further validated our findings using two replication cohorts, Simons Simplex Collection (SSC) and MSSNG, and showed the consistent enrichment of non-coding DNM-disrupted chromatin interactions in ASD probands. Generating human induced pluripotent stem cells in two ASD families, we were able to demonstrate that non-coding DNMs in chromatin interactions alter the expression of target genes at the stage of early neural development. Taken together, our findings indicate that non-coding DNMs in ASD probands lead to early neurodevelopmental disruption implicated in ASD risk via chromatin interactions.

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7. Larkin F, Ralston B, Dinsdale SJ, Kimura S, Hayiou-Thomas ME. Alexithymia and intolerance of uncertainty predict somatic symptoms in autistic and non-autistic adults. Autism;2022 (Jul 15):13623613221109717.

Autistic people have more physical health problems than non-autistic people. We were interested in whether autistic people experience more discomfort in their bodies than non-autistic people and whether certain psychological traits contribute to that. A survey was completed online by older adolescents and adults, 51 of whom were autistic, 32 of whom thought they might be autistic but were not diagnosed and 119 who were not autistic. They completed measures of somatic symptoms (daily experience of pain, discomfort, dizziness), alexithymia (difficulty identifying and expressing feelings), interoception (how much people are aware of their bodies) and intolerance of uncertainty (how people handle doubt or uncertainty), and reported any physical or mental health conditions. We found that the autistic participants had more physical and mental health conditions than the non-autistic participants, but even when we took account of this, they experienced higher levels of somatic symptoms. We looked at which psychological factors influenced levels of somatic symptoms across the whole sample, and found that alexithymia, intolerance of uncertainty, having physical health problems, being female and the number of mental health conditions predicted somatic symptoms, while interoception and autism diagnosis did not. The findings suggest that people may be more likely to experience physical discomfort if they are female, and have difficulty identifying and expressing feeling and difficulty tolerating doubt. As these psychological factors are more prominent in autism, we think this is important for physical and mental health providers to know about, so that these psychological factors can be considered when assessing and treating autistic people.

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8. Liljenwall H, Lean RE, Smyser TA, Smyser CD, Rogers CE. Parental ADHD and ASD symptoms and contributions of psychosocial risk to childhood ADHD and ASD symptoms in children born very preterm. J Perinatol;2022 (Jul 15)

OBJECTIVES: Examine maternal and paternal ADHD and ASD symptoms in relation to very preterm (VPT) and full-term (FT) children’s ADHD and ASD symptoms. STUDY DESIGN: In this longitudinal study, maternal- and teacher-report of child ADHD and ASD symptoms were obtained for 119 children (VPT = 79, FT = 40) at age 5-years using the Conner’s Rating Scale-Revised (CRS-R) and Social Responsiveness Scale-2 (SRS-2). A biological parent completed self- and observer-report CRS-R and SRS-2, and measures of mood/affect, stress, and social support to assess psychosocial distress. Data were analyzed using mixed-effect models adjusted for covariates. RESULTS: Child ADHD symptoms were associated with VPT birth, maternal distress, and maternal ADHD symptoms (p ≤ 0.02), and paternal ADHD symptoms (p < 0.001). Regarding ASD, VPT birth and parental ASD symptoms were associated with child ASD symptoms (p ≤ 0.009). Parental symptoms and birth group had no interaction. CONCLUSIONS: VPT birth and parental psychopathology represent independent risks for ADHD and ASD.

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9. Lilley R, Lawson W, Hall G, Mahony J, Clapham H, Heyworth M, Arnold S, Trollor J, Yudell M, Pellicano E. « Peas in a pod »: Oral History Reflections on Autistic Identity in Family and Community by Late-Diagnosed Adults. J Autism Dev Disord;2022 (Jul 14)

In this paper, we report on a participatory oral history study documenting the lives of late-diagnosed autistic adults in Australia. We interviewed 26 autistic adults about their life history and the impact of late diagnosis. All were diagnosed after the age of 35, growing up in an era when autism was not well known. Using reflexive thematic analysis, we uncovered a rich body of reflections on shared Autistic identity and identified three major themes within that data set: ‘conceptualising the Autistic family’, ‘creating Autistic community’, and ‘contesting Autistic identity’. Overall, the study provides insights into the active creation of shared Autistic identity and the importance of Autistic community to these late-diagnosed autistic adults.

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10. Litwin S, Sellen K. Designing a Sensory Kit to Improve the Environment for Children with Autism Spectrum Disorder in the Pediatric Emergency Department. J Autism Dev Disord;2022 (Jul 14)

Children with autism spectrum disorder (ASD) have more frequent use of healthcare services, including visits to the emergency department (ED). Medical care for children with ASD can be adversely affected by the highly stimulating environment of the ED. In this study, we gained insights from stakeholders with lived experience (parents of children with ASD, children with ASD, and ED healthcare providers) to create and implement a sensory equipment kit. The kit was evaluated and iteratively improved based on observations of children using the sensory equipment, satisfaction surveys from their parents, and interviews with healthcare providers in the ED. Findings from this study can be used to guide other EDs in creating their own ASD sensory kit.

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11. Mellahn OJ, Knott R, Tiego J, Kallady K, Williams K, Bellgrove MA, Johnson BP. Understanding the Diversity of Pharmacotherapeutic Management of ADHD With Co-occurring Autism: An Australian Cross-Sectional Survey. Front Psychiatry;2022;13:914668.

OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) frequently co-occurs with other neurodevelopmental diagnoses, such as autism spectrum disorder (autism), which can make clinical decision making around symptom management challenging for clinicians. There is a paucity of research examining pharmacotherapeutic management of children who have ADHD with co-occurring diagnoses. We aimed to report on the co-occurring diagnoses and symptom profile of children, and report on medication use, stratified by ADHD, autism and ADHD + autism diagnoses. METHODS AND MATERIALS: Caregivers of 505 children (2-18 years) with ADHD (n = 239), autism (n = 117), and co-occurring ADHD + autism (n = 149) completed a questionnaire on current medication use and clinical rating scales about their child’s symptoms, as part of a broader project investigating diagnosis and management of symptoms in children with ADHD or autism. RESULTS: The parents of the ADHD group reported a higher proportion of their children had learning disorders (17.15%) and speech and language disorders (4.60%) compared to the parents of the autism and ADHD + autism groups. Parents of the ADHD + autism group reported higher proportions of intellectual disability (5.37%), oppositional defiant disorder (20.13%), anxiety (38.93%), depression (6.71%) and genetic conditions (3.36%) in their children, in comparison to the parents of the ADHD and autism groups. Children with ADHD were reported to be taking a higher proportion of psychotropic medication (90%), followed by ADHD + autism (86%) and autism (39%). The parents of children with ADHD + autism reported a higher proportion of non-stimulant ADHD medication (25.5%), antipsychotic (18.79%), antidepressant (22.15%) and melatonin (31.54%) use by their children, compared to the parents of the ADHD and autism groups. CONCLUSIONS: A similar proportion of children with ADHD + autism and ADHD were reported to be taking medication. However, the types of medication taken were different, as expected with reported co-occurring diagnoses. The complexity of symptoms and diagnoses in ADHD + autism warrants targeted research to optimize management and therapeutic outcomes.

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12. Qiao H, Tian Y, Huo Y, Man HY. Role of the DUB enzyme USP7 in dendritic arborization, neuronal migration, and autistic-like behaviors in mice. iScience;2022 (Jul 15);25(7):104595.

Duplication and haploinsufficiency of the USP7 gene are implicated in autism spectrum disorders (ASD), but the role for USP7 in neurodevelopment and contribution to ASD pathogenesis remain unknown. We find that in primary neurons, overexpression of USP7 increases dendritic branch number and total dendritic length, whereas knockdown leads to opposite alterations. Besides, USP7 deubiquitinates the X-linked inhibitor of apoptosis protein (XIAP). The USP7-induced increase in XIAP suppresses caspase 3 activity, leading to a reduction in tubulin cleavage and suppression of dendritic pruning. When USP7 is introduced into the brains of prenatal mice via in utero electroporation (IUE), it results in abnormal migration of newborn neurons and increased dendritic arborization. Importantly, intraventricular brain injection of AAV-USP7 in P0 mice leads to autistic-like phenotypes including aberrant social interactions, repetitive behaviors, as well as changes in somatosensory sensitivity. These findings provide new insights in USP7-related neurobiological functions and its implication in ASD.

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13. Qin X, Li P, Wu Y, Wang X, Yan S, Xu Y, Zhu P, Hao J, Tao F, Huang K. Impact of caesarean delivery on children’s autism-like behaviours: the mediation of exclusive breastfeeding. Int Breastfeed J;2022 (Jul 15);17(1):53.

BACKGROUND: The rate of autism spectrum disorder (ASD) has been rising worldwide, and therefore it is important to identify potential causes of ASD to facilitate early prevention. This study examined the role of breastfeeding and the association between caesarean delivery (CD) and children’s autism spectrum disorder. METHODS: The data were from the Ma’anshan birth cohort (MABC) in China, that was set up between May 2013 and September 2014. Women within 14 gestational weeks were recruited. The delivery mode was extracted from medical notes and infant feeding was obtained from questionnaire surveys. Autism-like behaviour was assessed using the Checklist for Autism in Toddlers (CHAT-23) when children were 18 months old, and 3 years of age. At 5 years of age, autism-like behaviour was assessed using the Clancy Autism Behavior Scale behavior. Structural equation models tested the mediation effects of breastfeeding between CD and children’s autism spectrum disorder. RESULTS: In all, 1520 (48.89%) women gave birth via CD, and 406 (13.86%) children were identified with autism-like behaviours at 18 months. Compared with women giving birth via vaginal delivery, those giving birth via CD were more likely to experience a higher proportion of delayed initiation of breastfeeding (p < 0.01), and delayed onset of lactogenesis (p < 0.01). CD was associated with a lower proportion of exclusive breastfeeding at 4 months after delivery (p = 0.02). Autism-like behaviour was less likely amongst infants with exclusively breastfeeding at 4 months than amongst those not exclusively breastfeeding at 4 months (p < 0.01). SEM indicated that women who gave birth by CD were more likely to stop exclusive breastfeeding in the first 4 months (standard estimations = - 0.04, p = 0.02), and those children who were not exclusively breastfed at 4 months were more likely to have autism-like behaviours (standard estimations = - 0.05, p < 0.01). The associations persisted at 3 years, but not at 5 years. CONCLUSIONS: Exclusive breastfeeding at 4 months of age mediated the association between caesarean delivery and children's autism-like behaviours.

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14. Saré RM, Song A, Levine M, Lemons A, Loutaev I, Sheeler C, Hildreth C, Mfon A, Smith CB. Behavioral and Molecular Consequences of Chronic Sleep Restriction During Development in Fragile X Mice. Front Neurosci;2022;16:834890.

Sleep is critical for brain development and synaptic plasticity. In male wild-type mice, chronic sleep restriction during development results in long-lasting impairments in behavior including hypoactivity, decreased sociability, and increased repetitive behavior. Disordered sleep is characteristic of many neurodevelopmental disorders. Moreover, the severity of behavioral symptoms is correlated with the degree of disordered sleep. We hypothesized that chronic developmental sleep restriction in a mouse model of fragile X syndrome (FXS) would exacerbate behavioral phenotypes. To test our hypothesis, we sleep-restricted Fmr1 knockout (KO) mice for 3 h per day from P5 to P52 and subjected mice to behavioral tests beginning on P42. Contrary to our expectations, sleep restriction improved the hyperactivity and lack of preference for social novelty phenotypes in Fmr1 KO mice but had no measurable effect on repetitive activity. Sleep restriction also resulted in changes in regional distribution of myelin basic protein, suggesting effects on myelination. These findings have implications for the role of disrupted sleep in the severity of symptoms in FXS.

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15. Tenenbaum A, Arbel Alon S. [INTELLECTUAL AND DEVELOPMENTAL DISABILITY: CHANGING THE HEBREW ABBREVIATIONS – WORDS MATTER]. Harefuah;2022 (Jul);161(7):461-462.

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16. Torske T, Nærland T, Quintana DS, Hypher RE, Kaale A, Høyland AL, Hope S, Johannessen J, Øie MG, Andreassen OA. Sex as a Moderator Between Parent Ratings of Executive Dysfunction and Social Difficulties in Children and Adolescents with Autism Spectrum Disorder. J Autism Dev Disord;2022 (Jul 15)

Girls and boys might differ in autistic symptoms and associated cognitive difficulties such as executive function (EF). We investigated sex differences in the relationship between parent rated EF and autistic symptoms in 116 children and adolescents (25 girls) aged 5-19 years with an intelligence quotient above 70 and an autism spectrum disorder (ASD) diagnosis. They were rated with the behavior rating inventory of executive function (BRIEF) and the autism diagnostic interview revised (ADI-R). We found a positive association between EF and the ADI-R domains of reciprocal social interaction (p < 0.001) and communication (p = 0.001) in girls, while these relationships were small and non-significant in boys. Our results provide a greater understanding of the sex-specific characteristics of children and adolescents with ASD.

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17. Traut N, Heuer K, Lemaître G, Beggiato A, Germanaud D, Elmaleh M, Bethegnies A, Bonnasse-Gahot L, Cai W, Chambon S, Cliquet F, Ghriss A, Guigui N, de Pierrefeu A, Wang M, Zantedeschi V, Boucaud A, van den Bossche J, Kegl B, Delorme R, Bourgeron T, Toro R, Varoquaux G. Insights from an autism imaging biomarker challenge: Promises and threats to biomarker discovery. Neuroimage;2022 (Jul 15);255:119171.

MRI has been extensively used to identify anatomical and functional differences in Autism Spectrum Disorder (ASD). Yet, many of these findings have proven difficult to replicate because studies rely on small cohorts and are built on many complex, undisclosed, analytic choices. We conducted an international challenge to predict ASD diagnosis from MRI data, where we provided preprocessed anatomical and functional MRI data from > 2,000 individuals. Evaluation of the predictions was rigorously blinded. 146 challengers submitted prediction algorithms, which were evaluated at the end of the challenge using unseen data and an additional acquisition site. On the best algorithms, we studied the importance of MRI modalities, brain regions, and sample size. We found evidence that MRI could predict ASD diagnosis: the 10 best algorithms reliably predicted diagnosis with AUC∼0.80 – far superior to what can be currently obtained using genotyping data in cohorts 20-times larger. We observed that functional MRI was more important for prediction than anatomical MRI, and that increasing sample size steadily increased prediction accuracy, providing an efficient strategy to improve biomarkers. We also observed that despite a strong incentive to generalise to unseen data, model development on a given dataset faces the risk of overfitting: performing well in cross-validation on the data at hand, but not generalising. Finally, we were able to predict ASD diagnosis on an external sample added after the end of the challenge (EU-AIMS), although with a lower prediction accuracy (AUC=0.72). This indicates that despite being based on a large multisite cohort, our challenge still produced biomarkers fragile in the face of dataset shifts.

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18. Yao Y, Uddin MN, Manley K, Lawrence DA. Improvements of autism-like behaviors but limited effects on immune cell metabolism after mitochondrial replacement in BTBR T(+)Itpr3(tf)/J mice. J Neuroimmunol;2022 (Jul 15);368:577893.

Mitochondria-mediated metabolic impairment and dysfunction are highly related with autism. Herein, the mitochondria-mediated metabolism of BTBR T(+)Itpr3(tf)/J (BTBR) mice with autistic-like behaviors was investigated. A new BTBR-mt(B6) strain generated by deriving BTBR mice with C57BL/6J (B6) mitochondria was used to determine the role of the mitochondrial genome. The BTBR-mt(B6) mice had improved social behaviors, higher levels of glutamate and astrocytes in the brain and less neuroinflammation than the BTBR mice; however, many of the metabolic parameters of BTBR mice such as enhanced fatty acid β-oxidation and lower glycolysis and glutaminolysis in immune cells compared to B6 mice were not or only partial improved in the BTBR-mt(B6) strain. The BTBR and BTBR-mt(B6) mice also had equivalent ETC (enhanced electron transport chain) activity of mitochondria, with an increase of reactive oxygen species (ROS) and decreased mitochondrial membrane potential compared to the B6 mice. The results suggest that the mitochondrial replacement with its metabolic alterations affect brain functions more than peripheral immune cell activities.

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