Khalife, M. | bioRxiv Science

bioRxiv2024

Disrupted Hippocampal-Prefrontal Networks In A Rat Model Of Fragile X Syndrome: A Study Linking Neural Dynamics To Autism-Like Behavioral Impairments

Fragile X Syndrome (FXS) is associated with autism spectrum disorder (ASD) symptoms that are associated with cognitive, learning, and behavioral challenges. We investigated how known molecular disruptions in the Fmr1 knockout (FMR-KO) rat model of FXS negatively impact hippocampal-prefrontal cortex (H-PFC) neural network activity and consequent behavior. MethodsFMR-KO and control rats underwent a battery of behavioral tests assessing sociability, memory, and anxiety. Single-unit electrophysiology recordings were then conducted to measure patterns of neural activity in H-PFC circuit. Advanced mathematical models were used to characterize the patterns that were then compared between groups using generalized linear mixed models. ResultsFMR-KO rats demonstrated significant behavioral deficits in sociability, spatial learning, and anxiety, aligning with symptoms of ASD. At the neural level, these rats exhibited abnormal firing patterns in the H-PFC circuit that is critical for learning, memory, and social behavior. The neural networks in FMR-KO rats were also less densely connected and more fragmented, particularly in hippocampal-PFC correlated firing. These findings suggest that disruptions in neural network dynamics underlie the observed behavioral impairments in FMR-KO rats. ConclusionFMR-KO significantly disrupts several characteristics of action potential firing in the H-PFC network, leading to deficits in social behavior, memory, and anxiety, as seen in FXS. This disruption is characterized by less organized and less resilient hippocampal-PFC networks. These findings suggest that therapeutic strategies aimed at normalizing neural dynamics, such as with brain stimulation, could potentially improve behavior and cognitive functions in autistic individuals. HIGHLIGHTSO_LIFragile X Syndrome is associated with autism, cognitive challenges and anxiety C_LIO_LIThe loss of Fmr1 protein disrupts processes involved in building neural networks C_LIO_LIThe consequence is abnormal neural dynamics in hippocampal-prefrontal cortex networks C_LIO_LINormalization of dynamics could improve outcomes in FXS and ASD C_LI

neuroscience↗

bioRxiv2023

Electrochemical biosensor based on NAD(P)H-dependent Quinone Reductase for rapid and efficient detection of vitamin K3

Vitamin K refers to a group of vitamins that play an important role in blood coagulation and regulation of bone and vascular metabolism. However, vitamin K3 may give severe side effects in animal and humans when improperly added to food and feed due to its toxicity. Here, an electrochemical biosensor, based on the YaiB NADPH-dependent quinone reductase from Lactococcus lactis (YaiB), was developed to achieve rapid and redox probe-free detection of vitamin K3. First, we demonstrated the ability of the carbon electrode to distinguish between 1,4-benzoquinone and hydroquinone. Then, we engineered YaiB to work as a bioreceptor immobilized at the electrode and we demonstrated its sensitivity and specificity to reduce vitamin K3. Finally, to demonstrate the practical potential of the biosensor, we tested it directly in spiked milk samples, achieving 15-minute quantification of the vitamin K3. The limit of detection was 0.18M and 0.86 M in buffer and milk, respectively.

biophysics↗