Understanding the Role of Perineuronal Nets in Developing Hippocampal Circuits in a Mouse Model of Fragile X Syndrome
Year: 2017
Type: article
Abstract: Fragile X Syndrome (FXS) is a leading cause of intellectual disability and autism.It is caused by an expansion of CGG repeats that leads to hypermethylation and silencing of Fragile X Mental Retardation (Fmr1) gene.Silencing of the Fmr1 gene results in the loss of Fragile X Mental retardation protein (FMRP), which can cause abnormal synaptic transmission.These deficits contribute to various FXS symptoms, including cognitive and learning impairments.However, the origins of these deficits remain unknown.Fmr1 KO mice were used in this study to understand the mechanisms of learning impairments in FXS.The FXS Fmr1 KO mouse model exhibits an excitatory-inhibitory (E/I) imbalance, which suggest abnormal synaptic functions in areas such as the hippocampus, area of the brain responsible for learning.Previous studies in Fmr1 KO mice have demonstrated an increase in levels of matrix metalloproteinase-9 (MMP-9), an extracellular enzyme that cleaves extracellular matrix (ECM), including perineuronal nets (PNNs) and can affect synaptic transmission.PNNs act as scaffolds around inhibitory neurons, such as parvalbumin (PV) positive cells, to regulate their activity.Based on this evidence, the goal of this study is to determine if there is abnormal development of PV positive cells and PNNs in the hippocampus of Fmr1 KO mice.We hypothesized that if MMP-9 levels are elevated with FXS, genetic reduction of MMP-9 may reverse the deficits.The results of this pilot study indicate reduced density of PV cells in the CA1 subfield of the hippocampus in the Fmr1 KO mice compared to the WT mice.The results of this study may provide new insight into E/I imbalance in autism spectrum disorders and into the mechanisms of abnormal hippocampal development that may lead to learning deficits in FXS.
Author: Katherine Espinoza
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2771522484