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The Wnt/β-catenin pathway contains multiple high-confidence risk genes that are linked to neurodevelopmental disorders, including autism spectrum disorder. However, its ubiquitous roles across brain cell types and developmental stages have made it challenging to define its impact on neural circuit development and behavior. Here, we show that TCF7L2, which is a key transcriptional effector of the Wnt/β-catenin pathway, plays a cell-autonomous role in postnatal astrocyte maturation and impacts adult social behavior. TCF7L2 was the dominant Wnt effector that was expressed in both mouse and human astrocytes, with a peak during astrocyte maturation. The conditional knockout of Tcf7l2 in postnatal astrocytes led to an enlargement of astrocytes with defective tiling and gap junction coupling. These mice also exhibited an increase in the number of cortical excitatory and inhibitory synapses and a marked increase in social interaction by adulthood. These data reveal an astrocytic role for developmental Wnt/β-catenin signaling in restricting excitatory synapse numbers and regulating adult social behavior.

The number of people who cannot consume dairy products due to intolerance or allergies to food components is increasing. Consumers are increasingly searching for alternative, nondairy beverages which have an advantageous effect on the body and which stimulate gut microflora. Previous studies have shown that Streptococcus thermophilus T K M 3 KKP 2030p can be an efficient starter culture for the fermentation of plant material and can also ensure an acceptable sensory profile and a high number of lactic acid bacteria during 4 week cold storage. The aim of this study was to determine the relative gene expression of the l -lactate dehydrogenase gene ( ldhL) in selected strain using the RT qPCR technique at particular time points. The gene expression experiments were conducted in laboratory broth (LABm) and fruit–cereal (OBPromOat) matrix with a beta-glucan additive. Levels of gene relative expression in the selected strain in these two media were correlated with the amount of l -lactate produced. The results showed that the plant matrix stimulated stronger ldhL gene expression in the first 4 h of the experiment (although the synthesis of l -lactate was less than in laboratory broth). This study broadens existing knowledge of the transcriptional mechanisms which arise from the adaptation of the analyzed strain to different habitats during l -lactate synthesis. This could contribute to the development of new alternative food products for people who show intolerance to milk proteins or lactose.

The number of people who cannot consume dairy products due to intolerance or allergies to food components is increasing. Consumers are increasingly searching for alternative, nondairy beverages which have an advantageous effect on the body and which stimulate gut microflora. Previous studies have shown that Streptococcus thermophilus TKM3 KKP 2030p can be an efficient starter culture for the fermentation of plant material and can also ensure an acceptable sensory profile and a high number of lactic acid bacteria during 4 week cold storage. The aim of this study was to determine the relative gene expression of the l-lactate dehydrogenase gene (ldhL) in selected strain using the RT qPCR technique at particular time points. The gene expression experiments were conducted in laboratory broth (LABm) and fruit-cereal (OBPromOat) matrix with a beta-glucan additive. Levels of gene relative expression in the selected strain in these two media were correlated with the amount of l-lactate produced. The results showed that the plant matrix stimulated stronger ldhL gene expression in the first 4 h of the experiment (although the synthesis of l-lactate was less than in laboratory broth). This study broadens existing knowledge of the transcriptional mechanisms which arise from the adaptation of the analyzed strain to different habitats during l-lactate synthesis. This could contribute to the development of new alternative food products for people who show intolerance to milk proteins or lactose.

The number of people who cannot consume dairy products due to intolerance or allergies to food components is increasing. Consumers are increasingly searching for alternative, nondairy beverages which have an advantageous effect on the body and which stimulate gut microflora. Previous studies have shown that Streptococcus thermophilus T M KKP 2030p can be an efficient starter culture for the fermentation of plant material and can also ensure an acceptable sensory profile and a high number of lactic acid bacteria during 4 week cold storage. The aim of this study was to determine the relative gene expression of the L-lactate dehydrogenase gene (ldhL) in selected strain using the RT qPCR technique at particular time points. The gene expression experiments were conducted in laboratory broth (LABm) and fruit-cereal (OBPromOat) matrix with a beta-glucan additive. Levels of gene relative expression in the selected strain in these two media were correlated with the amount of L-lactate produced. The results showed that the plant matrix stimulated stronger ldhL gene expression in the first 4 h of the experiment (although the synthesis of L-lactate was less than in laboratory broth). This study broadens existing knowledge of the transcriptional mechanisms which arise from the adaptation of the analyzed strain to different habitats during L-lactate synthesis. This could contribute to the development of new alternative food products for people who show intolerance to milk proteins or lactose.

Psychiatric and metabolic disorders often co-occur. While shared genetic factors and cellular dysfunctions are implicated, the underlying molecular mechanisms remain poorly understood. TCF7L2, a risk gene for type 2 diabetes and autism spectrum disorder, is highly expressed in the thalamus—a brain region extensively interconnected with the cortex, playing a key role in sensory processing, motor control, and behavioral regulation. Given its known role as a transcription factor regulating systemic energy metabolism, we explored its potential contribution to brain metabolism and behavior. To this end, we used a conditional knockout model with postnatal TCF7L2 loss in the thalamus and partial deficiency in the pancreas. Tcf7l2 knockout mice exhibited social deficits and reduced motor habituation. In parallel, they also developed systemic glucose intolerance, modelling the psychiatric-metabolic comorbidity. Thalamic depletion of TCF7L2 resulted in elevated inhibitory phosphorylation of the pyruvate dehydrogenase —an enzymatic gatekeeper for pyruvate utilization in energy production—in the thalamus and cortex. This was accompanied by altered thalamic and cortical metabolism, characterized by reduced efficiency of pyruvate oxidation alongside enhanced oxidation of fatty acids and ketone bodies. Notably, a ketogenic diet alleviated metabolic dysregulation in the brain and normalized some social behaviors in knockout mice. These findings suggest that impaired energy metabolism in the thalamocortical circuitry may represent one of the pathogenic mechanisms underlying neuropsychiatric symptoms.