Behavioural disinhibition in frontotemporal dementia investigated within an ecological framework

Morandi, Xavier; Jannin, Pierre; Batrancourt, Bénédicte; Azuar, Carole; Dubois, Bruno; Lecouturier, Karen; Araujo, Carla M.; Janvier, Estelle; Jourdain, Aline; Rametti‐Lacroux, Armelle; Coriou, Sophie; Brochard, Vanessa B.; Gaudebout, Cécile; Ferrand-Verdejo, Johan; Bonnefous, L.; Pochan-Leva, Flore; Jeanne, Lucie; Joulié, Mathilde; Provost, Myriam; Renaud, Rozenn; Hachemi, Sarah; Guillemot, Vincent; Bendetowicz, David; Carle, Guilhem; Socha, Julie; Pineau, Fanny; Marin, Frédéric; Liu, Yongjian; Mullot, Pierre; Mousli, Aymen; Blossier, Armelle; Visentin, Giulia; Tanguy, Delphine; Godefroy, Valérie; Sezer, Idil; Boucly, Mathilde; Cabrol-Douat, Blandine; Odobez, Raphaëlle; Marque, Constance; Tessereau-Barbot, Daphné; Raud, Anaïs; Funkiewiez, Aurélie; Chamayou, Céline; Cognat, Emmanuel; Bozec, Manon Le; Bouzigues, Arabella; Du, Vincent Le; Bombois, Stéphanie; Simard, Camille; Fulcheri, Paolo; Guitton, Hortense; Peltier, Caroline; Lejeune, François‐Xavier; Jorgensen, Lars; Mariani, Louise‐Laure; Corvol, Jean‐Christophe; Valero‐Cabré, Antoni; Garcin, Béatrice; Volle, Emmanuelle; Ber, Isabelle Le; Migliaccio, Raffaella; Lévy, Richard

doi:10.1016/j.cortex.2022.11.013

Cited by 1 publication

(2 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Disinhibition is indeed a core symptom in bvFTD, and impulsivity, compulsivity, as well as social disinhibition are documented in the diagnostic criteria of the disease [69], as such reflecting the multifaceted nature of inhibitory deficits in patients. Moreover, even only recently, it has been argued that characterization of behavioral disinhibition in patients is still poorly detailed, and a universally accepted conception is still lacking [70,71]. As such, assessing behavioral disinhibition in rodent models should include a variety of setups and paradigms mimicking the umbrella concept in patients.…”

Section: Discussionmentioning

confidence: 99%

“…As previously discussed, Tau58 lines display stereotyped behavior, i.e., obsessive grooming indicative of increased compulsivity. Social disinhibition may manifest, for example, as aggressive behavior (hostility, verbal or physical aggression), inappropriate familiar or sexual behavior, as well as the loss of decorum in the clinical ethogram [70,71], which would prompt a more in-depth evaluation of various social behaviors in both lines in the future. Deficits in social exploration were reported in the Tau58/2 line from the age of 4 months onwards [26,35].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Behavioral and Neuropathological Phenotyping of the Tau58/2 and Tau58/4 Transgenic Mouse Models for FTDP-17

Van Dam,

Valkenburg,

Van Kolen

et al. 2023

Life

View full text Add to dashboard Cite

Background: The Tau58/2 and Tau58/4 mouse lines expressing 0N4R tau with a P301S mutation mimic aspects of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). In a side-by-side comparison, we report the age-dependent development of cognitive, motor, and behavioral deficits in comparison with the spatial-temporal evolution of cellular tau pathology in both models. Methods: We applied the SHIRPA primary screen and specific neuromotor, behavioral, and cognitive paradigms. The spatiotemporal development of tau pathology was investigated immunohistochemically. Levels of sarkosyl-insoluble paired helical filaments were determined via a MesoScale Discovery biomarker assay. Results: Neuromotor impairments developed from age 3 months in both models. On electron microscopy, spinal cord neurofibrillary pathology was visible in mice aged 3 months; however, AT8 immunoreactivity was not yet observed in Tau58/4 mice. Behavioral abnormalities and memory deficits occurred at a later stage (>9 months) when tau pathology was fully disseminated throughout the brain. Spatiotemporally, tau pathology spread from the spinal cord via the midbrain to the frontal cortex, while the hippocampus was relatively spared, thus explaining the late onset of cognitive deficits. Conclusions: Our findings indicate the face and construct validity of both Tau58 models, which may provide new, valuable insights into the pathologic effects of tau species in vivo and may consequently facilitate the development of new therapeutic targets to delay or halt neurodegenerative processes occurring in tauopathies.

show abstract

Section: Discussionmentioning

confidence: 99%