Sex as a Biological Variable in Striatal Circuit Plasticity and Pathology

The striatum is central to motor control, reward processing and several cognitive functions, all of which depend on synaptic plasticity within corticostriatal circuits. There is now consistent evidence that males and females differ in how this plasticity is established, maintained and remodelled, and that these differences track with the prevalence, age of onset and clinical course of disorders such as Parkinson’s disease, Huntington’s disease, depression and substance use disorders. Despite this, sex is still rarely treated as a biological variable in molecular studies of the striatum, and the cellular basis of sex-dependent vulnerability and resilience remains poorly defined.At the molecular level, gonadal hormones and sex chromosome complement act in parallel to shape striatal long-term potentiation and depression. Their effects converge on dopaminergic, glutamatergic, GABAergic and endocannabinoid signalling, on neurotrophic pathways such as BDNF/TrkB, and on the epigenetic regulation of synaptic genes. When these mechanisms are disrupted, the result is altered synaptic connectivity, loss of circuit homeostasis and, in many cases, a different response to pharmacological treatment in males and females. Work that connects these molecular changes to circuit-level and behavioural readouts, with sex analysed as a primary variable rather than a covariate, is still scarce. This Research Topic invites contributions that address the molecular and cellular mechanisms behind sex differences in striatal synaptic plasticity, and how those mechanisms shape the trajectory of neuropsychiatric and neurodegenerative disorders. We are particularly interested in studies that dissect how sex hormones, sex chromosome complement, genetic background or developmental timing influence synaptic structure and function in striatal circuits, and how these factors contribute to disease vulnerability, resilience or treatment response. We welcome articles addressing, but not limited to, the following themes:• Molecular and cellular mechanisms of sex-dependent striatal plasticity• Hormonal, genetic and epigenetic regulation of striatal synaptic function• Sex-specific dopamine, glutamate, GABA and endocannabinoid signalling in the striatum• BDNF and other neurotrophic pathways in striatal resilience and vulnerability• Structural and functional synaptic changes in males and females across development and ageing• Hormonal and developmental shaping of corticostriatal maturation• Sex differences in striatal circuit remodelling in neuropsychiatric and neurodegenerative disease• Preclinical and translational models that integrate molecular, hormonal and behavioural data Topic editors: Adele Stewart, Tara A LeGates Source: https://www.frontiersin.org/research-topics/81143/sex-as-a-biological-variable-in-striatal-circuit-plasticity-and-pathology