Aug 2026· Neurobiology of Disease· pp.
107558
· 0 citations· 32 references
Medicine
TL;DR
It is demonstrated that ASD-related alterations are not static but evolve across adulthood, revealing a multi-level reorganization of behavioral, synaptic, and structural features.
Abstract
Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and the presence of restricted and repetitive behaviors. While ASD has a neurodevelopmental origin, it remains a lifelong condition, yet little is known about how its behavioral and neural features evolve across adulthood. Here, we investigated behavioral, synaptic, and structural alterations across the transition from early to mature adulthood in Cntnap2 knockout mice, a widely used model of ASD. Using a longitudinal behavioral approach combined with electrophysiological recordings and morphological analysis, we show that KO mice exhibit increased stereotyped and repetitive behaviors and reduced exploratory activity at both ages. However, detailed analysis of behavioral patterns revealed age-dependent differences, with early adult KO mice displaying increased behavioral persistence that later evolved into distinct patterns of behavioral sequences. These behavioral changes were associated with alterations in inhibitory synaptic transmission in the dorsolateral striatum (DLS), including changes in spontaneous inhibitory postsynaptic current (sIPSC) frequency and temporal structure. In parallel, mature adult KO mice showed structural remodeling of spiny projection neurons, characterized by increased distal dendritic arborization and age-dependent organization of dendritic spines. Together, our findings demonstrate that ASD-related alterations are not static but evolve across adulthood, revealing a multi-level reorganization of behavioral, synaptic, and structural features. These results highlight the importance of considering adulthood stages in ASD and provide new insights into the dynamic nature of the condition.
Boosting tonic inhibition from birth with chronic treatment with the GABAA receptor agonist gaboxadol fully reversed social deficits, restored the integrity of vocal circuits, and the multimodal integration of sensory inputs.
Lorenzo Ciano, Sebastian Sulis Sato, F. Galluzzi et al.· Molecular Psychiatry· 0 citations
The vesicular acetylcholine transporter knockdown (VAChT-KD) mouse is a genetic model of congenital myasthenic syndrome (CMS) characterized by impaired cholinergic transmission at the neuromuscular junction, resulting in presynaptic neuromuscular dysfunction. Here, we performed a longitudinal behavioral analysis to determine the onset and progression of motor deficits across development and adulthood, including potential sex-dependent effects. VAChT-KD mice exhibited early and persistent motor impairments. Neonatal animals showed reduced strength, impaired coordination, and delayed motor development compared to controls, and these deficits persisted into adulthood. Motor performance was consistently impaired in tests of global strength, while other behavioral measures revealed age- and sex-dependent differences. Notably, repeated exposure to motor tasks improved performance in mutant mice, indicating a learning component that partially compensates for underlying deficits. Across behavioral paradigms, genotype and age emerged as the primary determinants of motor performance. Importantly, the identification of early disease onset and measurable functional deficits across development highlights a critical window for therapeutic intervention. These findings support the use of VAChT-KD mice as a translational platform for testing early-stage therapies and underscore the importance of considering behavioral adaptation when designing preclinical studies for neuromuscular disorders.
L. A. Barbosa, K. Santos, Gabriel Marques et al.· Behavioural Brain Research· 0 citations
It is demonstrated that Cry1Δ11 mice exhibit robust repetitive behaviors, including excessive self-grooming and stereotyped rearing, which are associated with increased activity of DRD1-MSNs in the dorsolateral striatum, thereby identifying aberrant DRD1 signaling in the dorsolateral striatum as a promising target for therapeutic intervention.
Xiran Liu, Dengfeng Liu, Bingyu Long et al.· Translational Psychiatry· 0 citations
Results suggest that Adgrd1 plays a key role in maintaining hippocampal resilience and regulating motivational behaviors through integrated molecular and circuit-level mechanisms.
Inés Martínez-Soria, Pol Picón-Pagès, A. P. Pérez González et al.· bioRxiv· 0 citations
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social behavior and cognition. Increasing evidence suggests that alterations in dopaminergic neurotransmission, including changes in dopamine transporter (DAT) function, may contribute to ASD-related behavioral abnormalities. This study investigated whether selective DAT inhibition during early postnatal development influences behavioral and molecular alterations in a rat model of ASD induced by prenatal exposure to sodium valproate (NaVP). Pregnant Wistar rats received NaVP (600mg/kg, i.p.) on gestational day 12.5. Male offspring were treated with the selective DAT inhibitor CE-123 (10mg/kg, i.p.) once daily from postnatal day (PND) 10 to 23. Behavioral assessments during adolescence (PND25-42) evaluated social interaction, recognition memory, spatial preference, anxiety-like behavior, locomotor activity, and aversive memory. DAT, dopamine D2 receptor, brain-derived neurotrophic factor (BDNF), and interleukin-1β (IL-1β) protein expression were assessed in selected brain regions. Prenatal NaVP exposure impaired social novelty discrimination, declarative, spatial, and aversive memory, reduced locomotor activity, and increased anxiety-like behavior. These behavioral alterations were accompanied by elevated DAT and dopamine D2 receptor expression. Early postnatal CE-123 treatment attenuated several ASD-like behavioral abnormalities, normalized DAT and dopamine D2 receptor expression, increased BDNF levels in the prefrontal cortex (PFC), and increased IL-1β expression, without inducing non-specific locomotor stimulation. Together, these findings demonstrate that early postnatal CE-123 treatment was associated with long-lasting behavioral improvements accompanied by alterations in dopaminergic markers and BDNF expression. Although these findings support a role for dopaminergic regulation and neuroplasticity in the observed behavioral effects, the underlying mechanisms require further investigation.
The results suggest that adolescent risperidone treatment induces lasting transcriptomic and functional changes associated with altered excitatory-inhibitory neuronal interactions that may underline cognitive and behavioral dysregulations.
Abneil D Alicea-Pauneto, Hyowon Choi, Wenyu Zhang et al.· Neuropsychopharmacology· 0 citations
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