Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and communication, along with repetitive and restrictive patterns of behaviors or interests. Normal brain development is crucial to behavior and cognition in adulthood. Abnormal brain development, such as synaptic and myelin dysfunction, is involved in the pathogenesis of ASD. Microtubules and microtubule-associated proteins (MAPs) are important in regulating the processes of brain development, including neuron production and synaptic formation, as well as myelination. Increasing evidence suggests that the level of MAPs are changed in autistic patients and mouse models of ASD. Here, we discuss the roles of MAPs.

Autism spectrum disorder (ASD) is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. The BTBR T Itpr3 (BTBR) mice have emerged as a well characterized and widely used mouse model of a range of ASD-like phenotype, showing deficiencies in social behaviors and unusual ultrasonic vocalizations as well as increased repetitive self-grooming. However, the inherited neurobiological changes that lead to ASD-like behaviors in these mice are incompletely known and still under active investigation. The aim of this study was to further evaluate the structure and neurotransmitter release of the glutamatergic synapse in BTBR mice. C57BL/6J (B6) mice were used as a control strain because of their high level of sociability. The important results showed that the evoked glutamate release in the cerebral cortex of BTBR mice was significantly lower than in B6 mice. And the level of vesicle docking-related protein Syntaxin-1A was reduced in BTBR mice. However, no significant changes were observed in the number of glutamatergic synapse, level of synaptic proteins, density of dendritic spine and postsynaptic density between BTBR mice and B6 mice. Overall, our results suggest that abnormal vesicular glutamate activity may underlie the ASD relevant pathology in the BTBR mice.

BackgroundAlkaline phosphatase (ALP) is associated with an increased risk of cardiovascular events and is closely related to adverse outcomes after stroke. However, the regional investigation into the associations of ALP with acute stroke (AS) outcomes is limited. This study aimed to identify the association between serum ALP levels and clinical outcomes 3 months after AS in the Xi'an district of China.MethodsWe enrolled all patients with AS from 4 hospitals in the Xi'an district from January to December 2015. ALP levels and related patient information were collected at admission, and the events of stroke outcomes were followed up 1 and 3 months after diagnosis. ALP levels were analyzed as continuous variables and quartiles (Q1–Q4). The outcomes included all-cause mortality, recurrent stroke, and poor functional outcomes (modified Rankin Scale score of 3–6) within 3 months. A multivariate logistic regression and interaction analyses were performed to evaluate the independent association between serum ALP level and 3-month stroke outcomes.ResultsOverall, 2,799 patients with AS were enrolled in this study. The mean age was 63.9 ± 12.5 years. In the Q4 (≥93.0 U/L) group, the incidences of all-cause mortality, recurrent stroke, and poor functional outcomes were 7.8, 2.7, and 24.9%, respectively. After being adjusted for confounding variables, patients in Q4 (≥93.0 U/L) were related to an increased risk of all-cause mortality [odds ratio (OR) = 2.17, 95% CI: 1.19–3.96; P = 0.011] and patients in Q3 (76.8–92.9 U/L) were related to a lower risk of recurrent stroke (OR = 0.37, 95% CI: 0.14–0.97; P = 0.043) at the 3-month time point, compared to those in Q2 (63.0–76.7 U/L). The optimal range of ALP for all-cause mortality was seen in Q2, with a nadir level of 70 U/L. However, differences were statistically insignificant between ALP levels and poor functional outcomes (P > 0.05). Moreover, there was no significant interaction between ALP levels and age, gender, drinking status, smoking status, or pneumonia (P > 0.05) for all outcomes.ConclusionNon-linear associations were observed between serum ALP levels and 3-month outcomes in patients with AS. It might be beneficial to reduce the risk of all-cause mortality and recurrent stroke by maintaining ALP at optimal ranges.

The BTBR T + Itpr3tf/J (BTBR) mouse has developmental disorders in the central nervous system and many aberrant neuroanatomical structures. However, identification of the pathological mechanisms underlying these abnormal neuroanatomical structures in the brains of BTBR mice is still lacking. Posttranslational modifications (PTMs) are known to be involved in the regulation of diverse cellular processes, and evidence shows that some types of PTMs are associated with the development of the central nervous system. In this study, we detected four novel PTMs in the cerebral cortex of BTBR mice as compared to C57BL/6 J (B6) mice using western blotting. Results revealed that lysine crotonylation and succinylation were elevated in the cerebral cortex of BTBR mice compared to levels in B6 mice. We speculate that elevated profiles of lysine crotonylation and succinylation may be involved in mechanisms related to neuroanatomical abnormalities in cerebral cortex of BTBR mice.

BackgroundThe relationship between baseline fasting blood glucose (FBG) levels and 1-year stroke recurrence in non-diabetic patients with acute cerebral infarction (ACI) is unclear. We aimed to clarify this relationship in non-diabetic patients with ACI.MethodsBaseline FBG levels and related information of the patients were collected at admission and the events of stroke recurrence were followed up 1, 3, 6, and 12 months after the patients were discharged. Baseline FBG levels were analyzed as continuous variables and quartiles (Q1–Q4). Multivariate Cox regression models and a two-piecewise linear regression model were used to investigate the relationship and determine the threshold effect between baseline FBG levels and 1-year stroke recurrence in non-diabetic patients with ACI.ResultsOverall, 1,634 non-diabetic patients with ACI were enrolled. After adjusting for potential confounding factors, the hazard is 2.24-fold higher in Q4 than those in Q2, being considered the reference in non-diabetic patients with ACI [hazard ratio (HR) = 2.24, 95%CI: 1.08–4.65, P = 0.031]. Plotting hazard ratios over baseline FBG levels suggested a J-shaped relationship for 1-year stroke recurrence. Further analysis revealed that the nadir value of baseline FBG levels is 4.6 mmol/L. The relationship was more significant in patients with atrial fibrillation than in those without (P for interaction = 0.009).ConclusionLower and higher baseline FBG levels may lead to an increased risk of 1-year stroke recurrence in non-diabetic patients with ACI as shown by a J-shaped curve with a nadir value of 4.6 mmol/L.