id_910. EFFECTS OF MULTIMODAL COMPOUND HBK-15 ON CA1 CYTOARCHITECTURE IN A MOUSE MODEL OF EXCITATORY HYPOFUNCTION
Paulina Dudzik1,2, Jorge Valero3,4,5, Carla Escudero-Solano3,4,5, Luís Antonia de Castro3,4, Angelika Jagielska1,2, David Pérez-Boyero3,4, Jimena Pérez-Arévalo3,4, Concepción Lillo3,4, Klaudia Lustyk1, Karolina Pytka1
1 Jagiellonian University Medical College, Faculty of Pharmacy, Chair of Pharmacodynamics, Laboratory of Experimental Neuropharmacology, Krakow, Poland
2 Jagiellonian University Medical College, Doctoral School of Medical and Health Sciences, Krakow, Poland
3 University of Salamanca, Salamanca, Spain
4 INCYL, Institute of Neuroscience of Castilla y León, Salamanca, Spain
5 IBSAL, Institute of Biomedical Research of Salamanca, Salamanca, Spain
INTRODUCTION: Hippocampal excitatory hypofunction has been implicated in cognitive deficits across multiple neuropsychiatric disorders. Excitatory impairments may alter the microglial state, contributing to persistent circuit dysfunction. Multimodal compounds, such as HBK-15, represent a potential strategy for addressing this complex pathophysiology by simultaneously engaging various targets that regulate neurotransmission. HBK-15 exhibits high affinity for the 5-HT1A, 5-HT7, and sigma-1 receptors.
AIM(S): Accordingly, this study aimed to assess the effects of HBK-15 on hippocampal microglia in a mouse model of MK-801-induced excitatory impairment.
METHOD(S): During the reversal phase of cognitive flexibility assessment, for eight days, adult male mice were treated daily with HBK-15 (0.625, 1.25, and 2.5 mg/kg), followed by MK-801 (0.15 mg/kg) administration. Microglial changes in the CA1 region of the hippocampus were evaluated using immunohistochemistry for Iba1. Volumetric estimations of the CA1 region were performed via Cavalieri’s method.
RESULTS: Exploratory analysis indicated that MK-801 administration was associated with a modest decrease in Iba1 immunoreactivity in the CA1 region compared to saline-treated controls, as reflected by a reduced area fraction covered by Iba1+ microglia. Treatment with HBK-15 appeared to normalize these deficits. Volumetric analysis showed no detectable effect of MK-801 on CA1 volume, however, HBK-15 at the lowest dose increased total CA1 volume compared with the control and MK-801 groups.
CONCLUSIONS: Preliminary findings suggest that HBK-15 modulates the structural organization in the CA1 region of the hippocampus, while its potential role in microglial responses requires further investigation.
FINANCIAL SUPPORT: Co-funded by the European Union under Erasmus+ Cooperation Partnership programme (2023-1-PL01-KA220-HED-000160284). Science and Innovation Spanish Ministry (PID2022-140525NB-I00 and PID2022-140456NB-I00). Strategic plans and strategic research programmes of excellence from the Regional Government of Castile and León, co-funded by the ERDF Operational Programme (CLU-2023-1-01).