ePoster

Impact of ventral hippocampal chondroitinase-ABC infusion on perineuronal nets and diffuse extracellular matrix in male Lister hooded rats

Jacob Juty, Rachel Grasmeder Allen, Jacco Renstrom, Jennifer Fletcher, Charlotte Taylor, John Gigg, Michael Harte, Tobias Bast
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Jacob Juty, Rachel Grasmeder Allen, Jacco Renstrom, Jennifer Fletcher, Charlotte Taylor, John Gigg, Michael Harte, Tobias Bast

Abstract

Perineuronal nets (PNNs) in the hippocampus primarily surround inhibitory interneurons. PNNs have been suggested to regulate synaptic plasticity and support GABAergic inhibition, and PNN disruption has been implicated in brain disorders, including schizophrenia. Yet, the cognitive and behavioural consequences of hippocampal PNN loss largely remain to be studied.The enzyme chondroitinase-ABC (chABC) degrades chondroitin-sulfate proteoglycans (CSPGs), a main component of PNNs and the diffuse extracellular matrix (ECM), and has been used to study PNN function in animal models.Here, we characterised hippocampal PNN expression in male Lister hooded rats and the impact of ventral hippocampal chABC infusion. Control rats were infused with penicillinase, an enzyme with no endogenous substrate. Sensorimotor testing indicated no major impact of ventral hippocampal chABC infusion on locomotor activity, startle reactivity, or prepulse inhibition (PPI), although group sizes were small. Post-mortem staining of CSPGs by WFA lectin histochemistry revealed that PNNs were mainly expressed in CA2/CA3 of dorsal hippocampus and CA1 of ventral hippocampus. ChABC-treated rats showed profound ablation of WFA-stained PNNs and of diffuse ECM CSPGs in the ventral to intermediate hippocampus. Immunohistochemistry revealed extensive chondroitin-4-sulfate (C4S) “stubs” (products of CSPG degradation by chABC), in the ventral to intermediate hippocampus of chABC-treated rats 1 day post-infusion. 10 days post-infusion, PNN staining had recovered to some extent, whereas the ECM CSPG staining remained attenuated and C4S-stub staining remained marked. Future work will assess the impact of ventral hippocampal PNN removal with chABC on selected cognitive and behavioural functions linked to the hippocampus and regional inhibitory function.

Unique ID: fens-24/impact-ventral-hippocampal-chondroitinase-abc-9d794304