Seven Posters, One Goal: Driving Neuroscience Forward

After months of intensive research, we’re unveiling a wealth of discoveries, breakthrough findings, and powerful new insights at the SfN conference. Whether you are attending or not, you can read below about the exciting results in our posters covering the topics of:

• Anxiety and GABA
• Migraine and Psilocybin
• Alzheimer's and ARTE10 Transgenics
• Schizophrenia and Amphetamines
• Hallucinogenics and Non-hallucinogenics in Sleep
• qEEG and Ketamine
• Attention and Levetiracetam

If you’re looking to accelerate your next therapy, you may be particularly interested in what we have explored and discovered this year.

Characterisation of GABA2/3 Positive Allosteric Modulators (PAMs) in Tests of Anxiety and Side Effect

Benzodiazepines (BZs), exemplified by diazepam (DZP) have been effective clinical treatments for forms of epilepsy and anxiety for decades, although issues such as sedation, tolerance and dependence restrict their value.

The present study was designed to profile the α2/α3-GABAAR PAMs darigabat (DGB), and TPA023B and the α3-GABAAR-selective PAM SAN711 in the conditioned emotional response (CER) test of anxiety, and the 5-choice serial reaction time task (5-CSRTT) to study attention and reaction time.

In short, the rat CER assay was able to demonstrate an anxiolytic-like profile of the α2/α3- and α3-GABAAR subtype-selective compounds darigabat, TPA023B and SAN711, all of which showed an improved side effect profile relative to the non-selective GABAAR PAM diazepam.

View the findings here

Study of the Effects of Psilocybin in Three Rat Preclinical Models of Migraine; Insights from the Trigeminovascular System

Despite advancements in migraine research, a significant fraction of migraineurs do not achieve sufficient pain relief, highlighting the need for development of further treatments.

This exciting work shows the results of Psilocybin treatment in three separate migraine models.

The results of these experiments explore the potential of Psilocybin treatment for migraine, inflammatory markers, and reversal of the mechanical allodynia apparent in migraines.

This poster and its results have received special recognition from the press and it is being highlighted by the conference! Reply to this email and we will send the full results to you as soon as the press release is completed.

Explore migraine capabilities

Behaviour and Biomarker Changes in ARTE10 Mice Reveal Translational Potential for Alzheimer’s Disease and Mood-Related Comorbidities

Alzheimer’s disease (AD) patients often suffer from prodromal and co-morbid mood symptoms including anxiety and agitation which evade current therapies.

The ARTE10 double transgenic mouse model, which expresses mutant forms of human APP (Swedish mutation) and human Presenilin 1 carrying the M146 mutation (PSEN1), serves as a translational preclinical model for studying Alzheimer’s disease.

Whilst research has primarily focused on cognitive changes and pathology in advanced stages of AD. Here we have comprehensively characterized the ARTE10 model for prodromal and disease state behavioural phenotypes and biomarkers.

The ARTE10 mouse model exhibits prodromal behavioural phenotypes related to AD including anxiety like behaviours, pronounced amyloid pathology and early detectable biomarkers.

The progression of several of these phenotypes and biomarkers with age strongly supports the translational potential of the ARTE10 Alzheimer’s disease model.

See the data here

Phenotyping the DISC1 Rat Model of Schizophrenia Using PPI, Amphetamine-Induced Hyperlocomotion, Sleep-EEG and 40Hz ASSR

Schizophrenia is a devastating lifelong psychiatric condition for which there is currently no cure, and symptomatic treatments with varying degrees of efficacy and side-effects.

Presence of the Disrupted in Schizophrenia 1 (DISC1) protein is a known risk factor for schizophrenia, and in the tgDISC1 rat, overexpression of the DISC1 transgene produces neuronal DISC1 aggregates and a number of phenotypes consistent with the human condition.

Nine male tgDISC1 rats and seven male littermate controls were tested in pre-pulse inhibition (PPI), sleep-EEG, 40 Hz auditory steady-state response (ASSR), and amphetamine-induced hyperlocomotion (0.3mg/kg IP).

Our findings indicate the potential for the tgDISC1 rat in drug discovery for schizophrenia.

Review the research here

The Effects of LSD and Its Non-Hallucinogenic Analogue 2-Br-LSD on Murine Behavior, Sleep Patterns, and Quantitative EEG

Pharmacotherapy for depression and anxiety faces challenges such as delayed onset of action, the necessity for long-term treatment, and treatment-resistant patient populations.

Psychedelics offer an exciting, novel approach to tackling these issues. However, intense hallucinogenic effects can limit therapeutic applications.

Non-hallucinogenic alternatives that retain therapeutic efficacy could solve these challenges.

We compared the effects of LSD (Lysergic acid diethylamide) and its analogue 2-Br-LSD on sleep, neural activity and behaviour in male C57Bl/6 mice. We measured hallucinogenic effects in terms of head twitch responses (HTR), along with locomotion and rearing, using the LABORAS system.

Discover the results here

Drug Effects on Sleep Architecture and qEEG: A Cross-Species Comparison in Mice, Rats and Dogs.

The mechanisms controlling sleep and neuronal network oscillations are highly conserved across mammalian species, and are therefore ideal assays for translational research supporting drug discovery in both animals and humans.

The ease with which sleep and electroencephalography (EEG) can be measured also makes them suitable for use as pharmacodynamic biomarkers both clinically and preclinically.

The findings demonstrate that with consistent electrode placement and automated analysis, sleep-EEG provides a robust, cross-species tool for assessing pharmacodynamics, target engagement, and dose equivalence in both preclinical and clinical studies.

View the poster here

A Drug for All Ages: Levetiracetam Enhances Attention in Both Young and Aged Rats

Levetiracetam (LEV) is an antiepileptic primarily used to treat seizure disorder, but could it have therapeutic uses for treatment of some cognitive disorders such as mild cognitive impairment, early Alzheimer’s disease, or Autism Spectrum Disorder (ASD)?

To evaluate this, we tested young and aged Long-Evans rats and found that while the aged rats exhibited decline in attention or performance, in contrast, the young rats showed poor response control.

These findings indicate that LEV may have therapeutic potential for mitigating cognitive decline across multiple clinical conditions whilst underscoring the importance of age as a biological variable in preclinical cognitive assessment.

Discover the findings here