Effects of the transient receptor potential cation channel 5 (TRPC5) inhibitor NU6027 on hippocampal neuronal death after traumatic brain injury

摘要

Proteomic analysis of wing-cut flies: Identification of novel protein associated with axonal regeneration and degeneration Genetic studies of autism spectrum disorder (ASD) have revealed multigene variations that converge on synaptic dys- function. Moreover, dysregulation of the synaptic excitation and inhibition (E/I) ratio in various brain regions have been implicated in ASD pathology. DOCK4, a gene at 7q31.1 that encodes the gua- nine nucleotide exchange factor Dock4, has been identified as a risk gene for ASD and other neuropsychiatric disorders. However, whether and how Dock4 disruption leads to ASD features through a synaptic mechanism remain unexplored. We generated and char- acterized a line of Dock4 knockout (KO) mice, which intriguingly displayed a series of ASD-like behaviors, including impaired social novelty preference, abnormal isolation-induced pup vocalizations, elevated anxiety, and perturbed object and spatial learning. Exam- ination in CA1 pyramidal neurons revealed that excitatory synaptic transmission was drastically attenuated in KO mice, which resulted into the decreased of E/I ratio. Notably, pharmacological activa- tion of NMDA (N-methyl-D-aspartate)-type glutamate receptors restored social novelty preference in Dock4 KO mice. Our find- ings reveal that Dock4 plays an important role in regulating social.