Delayed Outgrowth in Response to the BDNF and Altered Synaptic Proteins in Neurons From SHR Rats
Daniela M Marques1, Amanda S Almeida1, Catiane B A Oliveira1
1Departamento de Bioquímica, Programa de Pós-Graduação Em Ciências Biológicas-Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-anexo, Porto Alegre, RS, 90035-003, Brasil.
Insights
Neurons from an ADHD rat model show delayed development and reduced branching. These cells also exhibit altered protein levels and a diminished response to BDNF, offering insights into synaptic dysfunction and potential ADHD treatments.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with known alterations in brain development.
- Previous research indicates delayed cortical and subcortical development in children with ADHD.
Purpose of the Study:
- To investigate the in vitro development of frontal cortical neurons from an ADHD rat model (SHR) compared to controls (WKY).
- To assess the impact of BDNF treatment on these neurons and evaluate synaptic protein levels.
Main Methods:
- Cultured frontal cortical neurons from SHR and WKY rats were studied over time in vitro.
- Neurons were treated with BDNF at different developmental time points (DIV).
- Analysis included dendritic morphology, synaptic protein levels, and BDNF-related proteins.
Main Results:
- SHR neurons displayed reduced dendritic outgrowth and branching compared to WKY neurons.
- CREB levels decreased at 1 DIV, and SNAP-25 decreased at 5 DIV in SHR neurons.
- Exogenous BDNF treatment resulted in less dendritic branching in SHR neurons, unlike in WKY neurons.
Conclusions:
- ADHD model neurons exhibit developmental delays and altered synaptic protein expression.
- These neurons show a reduced response to BDNF, potentially linked to early transcription factor changes.
- This in vitro model offers a tool for studying ADHD-related synaptic dysfunction and evaluating therapeutic interventions.
Abstract:
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity symptoms. Neuroimaging studies have revealed a delayed cortical and subcortical development pattern in children diagnosed with ADHD. This study followed up on the development in vitro of frontal cortical neurons from Spontaneously hypertensive rats (SHR), an ADHD rat model, and Wistar-Kyoto rats (WKY), control strain, over their time in culture, and in response to BDNF treatment at two different days in vitro (DIV). These neurons were also evaluated for synaptic proteins, brain-derived neurotrophic factor (BDNF), and related protein levels. Frontal cortical neurons from the ADHD rat model exhibited shorter dendrites and less dendritic branching over their time in culture. While pro- and mature BDNF levels were not altered, the cAMP-response element-binding (CREB) decreased at 1 DIV and SNAP-25 decreased at 5 DIV. Different from control cultures, exogenous BDNF promoted less dendritic branching in neurons from the ADHD model. Our data revealed that neurons from the ADHD model showed decreased levels of an important transcription factor at the beginning of their development, and their delayed outgrowth and maturation had consequences in the levels of SNAP-25 and may be associated with less response to BDNF. These findings provide an alternative tool for studies on synaptic dysfunctions in ADHD. They may also offer a valuable tool for investigating drug effects and new treatment opportunities.
