The dopamine system has been characterized in motor function, goal-directed behaviors, and rewards. Recent studies recognize various dopamine system genes as being associated with autism spectrum disorder (ASD). However, how dopamine system dysfunction induces ASD pathophysiology remains unknown. In the present study, we demonstrated that mice with increased dopamine functions in the dorsal striatum via the suppression of dopamine transporter expression in substantia nigra neurons or the optogenetic stimulation of the nigro-striatal circuitry exhibited sociability deficits and repetitive behaviors relevant to ASD pathology in animal models, while these behavioral changes were blocked by a D1 receptor antagonist. Pharmacological activation of D1 dopamine receptors in normal mice or the genetic knockout (KO) of D2 dopamine receptors also produced typical autistic-like behaviors. Moreover, the siRNA-mediated inhibition of D2 dopamine receptors in the dorsal striatum was sufficient to replicate autistic-like phenotypes in D2 KO mice. Intervention of D1 dopamine receptor functions or the signaling pathways-related D1 receptors in D2 KO mice produced anti-autistic effects. Together, our results indicate that increased dopamine function in the dorsal striatum promotes autistic-like behaviors and that the dorsal striatum is the neural correlate of ASD core symptoms.

Emerging evidence has suggested that the gut microbiota contribute to brain dysfunction, including pathological symptoms of Alzheimer disease (AD). Microbiota secrete membrane vesicles, also called extracellular vesicles (EVs), which contain bacterial genomic DNA fragments and other molecules and are distributed throughout the host body, including blood. In the present study, we investigated whether bacteria-derived EVs in blood are useful for metagenome analysis in an AD mouse model. Sequence readings of variable regions of 16S rRNA genes prepared from blood EVs in Tg-APP/PS1 mice allowed us to identify over 3,200 operational taxonomic units corresponding to gut microbiota reported in previous studies. Further analysis revealed a distinctive microbiota landscape in Tg-APP/PS1 mice, with a dramatic alteration in specific microbiota at all taxonomy levels examined. Specifically, at the phylum level, the occupancy of p_Firmicutes increased, while the occupancy of p_Proteobacteria and p_Bacteroidetes moderately decreased in Tg-APP/PS1 mice. At the genus level, the occupancy of g_Aerococcus, g_Jeotgalicoccus, g_Blautia, g_Pseudomonas and unclassified members of f_Clostridiale and f_Ruminococcaceae increased, while the occupancy of g_Lactobacillus, unclassified members of f_S24-7, and g_Corynebacterium decreased in Tg-APP/PS1 mice. A number of genus members were detected in Tg-APP/PS1 mice, but not in wild-type mice, while other genus members were detected in wild-type mice, but lost in Tg-APP/PS1 mice. The results of the present study suggest that the bodily microbiota profile is altered in Tg-APP/PS1 mice, and that blood EVs are useful for the metagenome analysis of bodily microbiota in AD.

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Arbuscular mycorrhizal fungi (AMF) have mutualistic relationships with more than 80% of terrestrial plant species. This symbiotic relationship is ancient and would have had important roles in establishment of plants on land. Despite their abundance and wide range of relationship with plant species, AMF have shown low species diversity. However, molecular studies have suggested that diversity of these fungi may be much higher, and genetic variation of AMF is very high within a species and even within a single spore. Despite low diversity and lack of host specificity, various functions have been associated with plant growth responses to arbuscular mycorrhizal fungal colonization. In addition, different community composition of AMF affects plants differently, and plays a potential role in ecosystem variability and productivity. AMF have high functional diversity because different combinations of host plants and AMF have different effects on the various aspects of symbiosis. Consequently, recent studies have focused on the different functions of AMF according to their genetic resource and their roles in ecosystem functioning. This review summarizes taxonomic, genetic, and functional diversities of AMF and their roles in natural ecosystems.

Autism spectrum disorders (ASDs) are a heterogeneous group of psychiatric illness characterized by common core symptoms including sociability deficits and stereotyped behaviors. ASD is caused by various genetic and non-genetic factors. The genetic effects of autism-related genes are usually global and are presented with multiple symptoms, which hamper understanding of the mechanism through which the diverse causes of ASD produce common symptoms. In the present study, we demonstrate that genetic or molecular disruption of an array of molecular networks centered on adenylyl cyclase type-5 (AC5 or ADCY5) in the dorsal striatum produces autistic-like behaviors. AC5 knockout (KO) mice exhibit increased repetitive behaviors and sociability deficits, the two core domains of ASD, and that siRNA-mediated suppression of AC5 within the dorsal striatum is sufficient to replicate these behavioral phenotypes. Notably, the autistic-like behaviors of AC5 KO mice are rescued by blocking mGluR5 glutamate receptors within the dorsal striatum. Furthermore, pharmacological or siRNA-mediated inhibition of mGluR3, GluA and GluN glutamate receptors in the dorsal striatum in wildtype mice also induces autistic-like behaviors. Optogenetic inhibition of the prelimbic cortical neurons projecting to the dorsal striatum in AC5 KO mice rescues the deficits in social and object novelty preferences. Our results suggest that AC5 mutation produces autistic-like symptoms through the upregulation of mGluR5 functions in the dorsal striatum and that the dorsal striatum regulated by AC5 is a neural correlate responsible for core ASD symptoms.