Mancini, C. | Search bioRxiv

bioRxiv2026

Cortical plasticity of the tactile mirror system in borderline personality disorder

Individuals with borderline personality disorder (BPD) show alterations in empathic abilities, potentially involving automatic simulation processes supported by mirror-like mechanisms in the somatosensory domain. Within the tactile mirror system (TaMS), observing touch on another persons body activates cortical regions involved in tactile perception, including the primary somatosensory cortex (S1). Although mirror-like alterations have been suggested in BPD, the underlying mechanisms of plasticity remain underexplored. Here, we used a cross-modal paired associative stimulation (cm-PAS) protocol to investigate the plasticity mechanisms of TaMS functioning in BPD. Twenty-four individuals with BPD and 24 healthy controls (HCs) were included. Empathic abilities were assessed using self-report questionnaires. Participants performed tactile acuity and visuo-tactile spatial congruity (VTSC) tasks before and after a cm-PAS protocol. During cm-PAS, images of a hand being touched were paired with transcranial magnetic stimulation over the S1. The effects of cm-PAS were assessed on tactile acuity, as an index of S1 activity, and VTSC performance, as an index of TaMS functioning. Preregistered analyses revealed that patients with BPD tended to have lower cognitive empathy than HCs, with no significant cm-PAS effects on tactile acuity or VTSC performance in HCs, precluding between-group comparisons of plasticity effects. Exploratory analyses were conducted to further investigate potential sources of variability in the effects of cm-PAS, as well as the relationship between cognitive empathy and visuo-tactile processing as measure of TaMS functioning. Preregistered Stage 1 protocol: https://osf.io/sqnwd (date of in-principle acceptance: 25/06/2023).

neuroscience↗

bioRxiv2018

Mice harboring a SCA28 patient mutation in AFG3L2 develop late-onset ataxia associated with enhanced mitochondrial proteotoxicity.

Spinocerebellar ataxia 28 is an autosomal dominant neurodegenerative disorder caused by missense mutations affecting the proteolytic domain of AFG3L2, a major component of the mitochondrial m-AAA protease. However, little is known of the underlying pathogenetic mechanisms or how to treat patients with SCA28. Currently available Afg3l2 mutant mice harbour deletions that lead to severe, early-onset neurological phenotypes that do not faithfully reproduce the late-onset and slowly progressing SCA28 phenotype. Here we describe production and detailed analysis of a new knock-in murine model harbouring an Afg3l2 allele carrying the p.Met665Arg patient-derived mutation. Heterozygous mutant mice developed normally but signs of ataxia were detectable by beam test at 18 months. Cerebellar pathology was negative; electrophysiological analysis showed increased spontaneous firing in Purkinje cells from heterozygous mutants with respect to wild-type controls, although not statistically significant. As homozygous mutants died perinatally with evidence of cardiac atrophy, for each genotype we generated mouse embryonic fibroblasts (MEFs) to investigate mitochondrial function. MEFs from mutant mice showed altered mitochondrial bioenergetics, with decreased basal oxygen consumption rate, ATP synthesis and mitochondrial membrane potential. Mitochondrial network formation and morphology was also altered, in line with greatly reduced expression of Opa1 fusogenic protein L-isoforms. The mitochondrial alterations observed in MEFs were also detected in cerebella of 18-month-old heterozygous mutants, suggesting they may be a hallmark of disease. Pharmacological inhibition of de novo mitochondrial protein translation with chloramphenicol caused reversal of mitochondrial morphology in homozygous mutant MEFs, supporting the relevance of mitochondrial proteotoxicity for SCA28 pathogenesis and therapy development.

genetics↗