Rho Signaling in Synaptic Plasticity, Memory, and Brain Disorders

Abstract

Memory impairments are associated with many brain disorders such as autism, Alzheimer’s disease, and depression. Forming memories involves modifications of synaptic transmission and spine morphology. The Rho family small GTPases are key regulators of synaptic plasticity by affecting various downstream molecules to remodel the actin cytoskeleton. In this paper, we will review recent studies on the roles of Rho proteins in the regulation of hippocampal long-term potentiation (LTP) and long-term depression (LTD), the most extensively studied forms of synaptic plasticity widely regarded as cellular mechanisms for learning and memory. We will also discuss the involvement of Rho signaling in spine morphology, the structural basis of synaptic plasticity and memory formation. Finally, we will review the association between brain disorders and abnormalities of Rho function. It is expected that studying Rho signaling at the synapse will contribute to the understanding of how memory is formed and disrupted in diseases.

Analysis of Faecal Microbiota and Small ncRNAs in Autism: Detection of miRNAs and piRNAs with Possible Implications in Host–Gut Microbiota Cross-Talk

“…This latter is emerging as a key regulator of nervous system physiology also involved in nervous system diseases and injury [ 122 ]. Moreover, pathways directly connected with ASD are: “Long term depression” that, together with “Long-term potentiation”, are the key regulators of long-lasting synaptic plasticity at the basis of learning and memory and whose impairment is involved in many brain disorders, including ASD [ 123 , 124 ]; “Insulin signalling pathway” promotes neuronal circuit development and maturation to an extent that, since its safety/preliminary efficacy for the treatment of Rett syndrome has emerged, clinical trials to ameliorate ASD symptoms are ongoing [ 125 ].…”

Delta-Catenin as a Modulator of Rho GTPases in Neurons

“…While CA RhoA decreases spine length in mouse and rat hippocampal neurons, the effects of RhoA inhibition on spine morphology are less clear. DN RhoA increased spine length and reduced spine density in rat hippocampal neurons, increased spine density and spine length in mouse hippocampal neurons, and did not influence spine density in pyramidal neurons from rat hippocampal slices (Nakayama et al, 2000;Tashiro et al, 2000;Pilpel and Segal, 2004;Tashiro and Yuste, 2004;Impey et al, 2010;Murakoshi et al, 2011;Orefice et al, 2016;Zhang et al, 2021). These discrepancies may be caused by differences in neuron age, type, local levels of activity, definitions used for what constitutes dendritic spines, or distinctions in the extent of cell contact with other neurons or glia arising from non-equivalent plating densities (Govek et al, 2005).…”

Acrolein, an endogenous aldehyde induces synaptic dysfunction in vitro and in vivo: Involvement of RhoA/ROCK2 pathway

“…Therefore, synapses are considered crucial for the developmental function of the nervous system (Bae & Kim, 2017 ; Batool et al, 2019 ; Selkoe, 2002 ; Skaper et al, 2017 ). Recent studies demonstrated that a range of neurological diseases could be characterized by the pathological changes in synapses, including abnormal dendritic spine morphology, synaptic loss, and destruction of synaptic plasticity (Zhang, Ben Zablah, et al, 2021 ). The synapse density can be reduced by 15%–35%, while the loss of synapses in the hippocampus of AD patients can reach as high as 44%–55% (Skaper et al, 2017 ).…”