Summary: A new study using Knockout Sapap3 mice highlights the brain mechanisms that can lead trichotillomania or a hair warm -up disorder. These mice presented compulsive grooming, increased assault and stress -sensitive behaviors, reflecting human TTM features, especially in women.
Neuronal recordings have revealed a reduced activity of the core accumbens alongside the imbalances in dopamine receptors and a modification of synaptic protein interactions. The results suggest that targeting the function of the reward circuit and dopamine routes could open new therapeutic avenues for the compulsive hair warm -up.
Key facts
- Circuit dysfunction: The Knockout Sapap3 mice showed a reduced activity in the accumbens nucleus, a key reward and a region of control of habits.
- Dopamine desire: High dopamine and altered expression of D1 / D2 receptors can biaise the brain towards repetitive motor behaviors.
- Complex modulation: The oxytocin has reduced assault and grooming episodes, but paradoxically increased the total grooming time.
Why this counts
- Why this counts: Advance understanding of the neurobiology of trichotillomania, pointing to reward the circuit and the signaling of dopamine as central engines.
- How it aligns with previous research: Bases on previous studies connecting the dysfunction of central gray nuclei and compulsive grooming in TOC spectrum disorders.
- Future implications: Can shed light on the targeted treatments that balance the dopamine routes or modulate the signaling of oxytocin to reduce the absence of compulsive hair.
Source: Neuroscience News
Trichotillomania (TTM), or hair warm-up disorder, is a psychiatric condition often misunderstood classified among obsessive and compulsive and related disorders (OCRD) in the DSM-5.
Affecting approximately 1.7% of adults, TTM implies recurring desires to withdraw your own hair, causing significant hair loss and significant emotional distress.
Although behavioral therapies can help, pharmacological options are limited and its neurobiological foundations remain incompletely understood.
A new study using a genetically modified mouse model devoid of the Sapap3 gene – Print involved in compulsive grooming behaviors – fresh offers of brain circuits and molecular tracks that can drive TTM.
The work also examines the surprising, sometimes paradoxical effects of neuropeptide, oxytocin on compulsive behavior and social aggression.
SAPAP3 KNOCKOUT MICE MIRROR KEY Characteristics of TTM
SAPAP3 is an abundant synaptic scaffolding protein in central gray nuclei, including the accumbens nucleus (NAC), a center for reward and regulation of habits. The mice devoid of SAPAP3 presented a constellation of behaviors recalling the human TTM: prolonged grooming under stress, increased anxiety type behavior and increased social aggression.
Female Knock-out mice are treated even longer than men, echoing the strong female predominance observed in the clinical TTM.
Detailed behavioral tests have revealed that environmental stress – in this case, a lively light aversive – exacerbated these repetitive grooming patterns. In social dominance tests, SAPAP3 deficient mice frequently moved their wild -type counterparts, showing an aggressive and dominant advantage under a challenge.
Dopamine imbalance and hypoactivity of the circuit
To probe the neuronal base of these behaviors, the researchers used calcium imagery in fiber optic to monitor the activity of the NAC during grooming. The Knockout Sapap3 mice showed clearly reduced neural calcium peaks compared to witnesses, indicating lower activity levels in this key reward processing center.
Molecular analysis highlighted an imbalance in dopamine signaling: high levels of dopamine, an increase in the expression of D1 receptors and a reduced expression of D2 receptors in the NAC. This scheme suggests an overactivation of the “direct” pathway in average thorny neurons, potentially biaring the brain towards repetitive motor behaviors and in reward. The levels of the CREB transcription factor – known for amplifying stress -related responses – were also high.
The team has also identified a disruption of the interaction between SAPAP3 and SHANK3, another postsynaptic scaffolding protein. Interestingly, Shank3 levels have increased in Knockout mice, perhaps as a compensatory mechanism to maintain synaptic stability.
The complex role of oxytocin
Given the reputation of oxytocin to modulate social behavior and anxiety, researchers have tested its effects in Knockout Sapap3 mice. The results were complex: a single dose reduced the number of grooming fights and reduced aggression, but paradoxically increased the total time spent to grooming.
This double effect underlines the influence of the context and the dose of the hormone on the brain circuits.
Implications for research and treatment TTM
This study refines our understanding of the neurobiology of the TTM by highlighting the dysfunction of the NAC circuit, the imbalance of dopamine receptors and the interactions of synaptic proteins as potential motors in the heating of compulsive hair.
It also raises important questions about specific sex vulnerability, the functional role of the Sapap3 – Shank3 coupling, and if the modulation of oxytocin tracks could be therapeutically beneficial or counterproductive – depending on the treatment strategy.
The limits of the work, in particular small sample sizes, asymmetrical molecular analyzes, and the need for chronic treatment studies – make room for future research. But by integrating behavioral, molecular and circuit results, it approaches the field of targeted and biologically lit interventions for TTM.
About these news of research on neuroscience and trichotillomania
Author: Editorial team of new neuroscience
Source: Neuroscience News
Contact: Editorial team of new neuroscience – Neuroscience News
Picture: The image is credited with Neuroscience News
Original search: Open access.
“Exploration of the accumbens nucleus circuit and oxytocin therapy in a Sapap3 Trichotillomania Knockout mouse model ”by Yuan Wang et al. Scientific relationships
Abstract
Exploration of the accumbens nucleus circuit and oxytocin therapy in a Sapap3 Elimination mouse model
Trichotillomania (TTM), a sub-studied psychiatric disorder, was studied using Sapap3 KNOCKOUT (KO) mice to elucidate the core circuit dysfunction accumbens (NAC) and the therapeutic potential of oxytocin.
In reverse conditions, KO mice presented TTM type behavioral phenotypes compared to wild -type controls (WT): anxiety type behavior (reduced total distance 33328.45 ± 6703.97 mm vs wt 47787.22 ± 122221.33 mm; The duration of immobility 175.05 ± 54.46 s against WT 90.23 ± 70.22 s, all ppp
Calcium imagery has revealed neuronal hypoactivity of the NAC (Pic ΔF / F0: 2.44 ± 1.67% against WT 6.92 ± 2.08%, pp
(2) Disturbances of synaptic plasticity (overexpression CREB: 1.71 times, pp
The effects of oxytocin were paradoxical: acute administration exacerbated the total grooming duration (550.45 ± 33.65 s against basic ko 467.43 ± 94.98 s, pp
Sex laminated analysis revealed increased gravity of grooming in Ko female mice (the grooming duration 526.59 ± 25.69 s against male KO 408.26 ± 104.33 s, p
These results highlight the dysfunction of the NAC circuit and the complex effects of oxytocin in TTM, suggesting therapeutic targets while emphasizing the need to structure sex.
