Time：2023-02-03 10:27:27 View:
Anxiety disorder is regarded as one of the most common comorbidities among individuals with autism. The comorbidity of autism and anxiety disorder makes the clinical diagnosis and treatment of autism more complicated. An in-depth analysis of its pathogenesis is crucial for formulating new treatment strategies for autism. Taking into account the neurobiochemical molecular events of the brain and the key neural circuits has important clinical significance for clarifying the pathological mechanism of autism - anxiety disorder comorbidity.
January 23, 2023 the research group of Professor Han Feng from the School of Pharmacy of Nanjing Medical University and the research group of Professor Lu Yingmei from the School of Basic Medical Sciences jointly published an online article titled "Divergent projections of the prelimbic cortex mediate" in Molecular Psychiatry Research paper on autism- and anxiety-like behaviors. This study found that there are two groups of neurons with different spatial distributions in the prelimbic cortex (PL), and their downward circuits are respectively involved in mediating autism-like and anxiety-like behaviors. It also revealed that the functional abnormality of TMEM74 in the PL brain region may be a key molecular protein in the comorbidity of autism-anxiety disorder. This research provides a new comorbidity animal model for the study of autism-anxiety comorbidity. By integrating the study of neural circuits and neurobiochemistry, it offers a fresh perspective for further clarifying the pathological mechanism of autism-anxiety comorbidity.
Researchers first discovered that two neural circuits in which PL descends to the dorsal striatum (dSTR) and the basolateral amygdaloid nucleus (BLA) are respectively involved in mediating autism-like behavior and anxanxiety behavior. And the pyramidal neurons directed towards the two downstream brain regions have different spatial distribution characteristics in the PL brain region. Importantly, the researchers further discovered that Tmem74-/- mice exhibited autistic and anxiety-like behavioral manifestations, with abnormally elevated excitability of pyramidal neurons in the PL brain region. However, chemogenetic inhibition of the abnormally elevated neuronal excitability could alleviate the autistic behavior in the mice. To further verify that Tmem74 is involved in mediating the above pathological phenotypes, researchers confirmed through CRISPR/Cas9 technology that TMEM74-specific knockout mice of pyramidal neurons in the PL brain region have abnormal electrophysiological characteristics and autistic and anxieast-like behaviors similar to those of Tmem74-/- mice. Finally, the researchers also found that overexpression of Tmem74 in pyramidal neurons in the PL brain region could alleviate autistic and anxiety-like behaviors in mice.
In summary, this study simulates the real pathological process of the comorbidity of autism and anxiety in clinical practice, integrates the two dimensions of neural circuit regulation and neurobiochemical changes, clarifies the pathogenesis of the comorbidity of autism and anxiety, and is expected to provide a brand-new potential therapeutic target for the treatment of the comorbidity of autism and anxiety.
Professor Han Feng from the School of Pharmacy and Professor Lu Yingmei from the School of Basic Medical Sciences of Nanjing Medical University are the co-corresponding authors. The first authors of the paper are Luo Yifan, a doctoral student, and Lu Lu, a master's student, from the School of Pharmacy. The academic papers of this team in recent years have been published in journals such as Neuron, J Clin Invest, J Exp Med, Cell Res, and Signal Transduct Target Ther.