Effects of hippocampal overexpression of LINGO-1 on learning and memory abilities and Spinophilin+ dendritic spines in different hippocampal subregions of mice

Abstract

Objective To investigate the effects of adenovirus-associated virus (AAV)-mediated overexpression of LINGO-1 in the hippocampus on spatial learning and memory abilities, as well as the volume and Spinophilin+ dendritic spines of different subregions within the hippocampus in mice. Methods Male C57 mice at 7 months of age were randomly divided into a control group and a LINGO-1 overexpression group. The control group received hippocampal stereotaxic injection of AAV carrying green fluorescent protein (GFP), while the LINGO-1 overexpression group received hippocampal stereotaxic injection of AAV carrying both GFP and LINGO-1 overexpression vector. Morris water maze was used to evaluate spatial learning and memory abilities of the mice. Quantitative PCR and immunofluorescence staining were used to detect LINGO-1 mRNA expression and fluorescence intensity in the hippocampus, and 3-dimensional stereology was used to quantify the volume and the total number of Spinophilin+ dendritic spines. Results There was no significant difference in body weight between the control group and the LINGO-1 overexpression group before and after virus injection. LINGO-1 overexpression induced an increase in hippocampal LINGO-1 at mRNA level and in fluorescent intensity(P < 0.01). The LINGO-1 overexpression group performed significantly worse in the Morris water maze test compared to the control group(P < 0.05). Moreover, LINGO-1 overexpression led to a significant reduction in the volumes of different hippocampal subregions(P < 0.05, P < 0.01), accompanied by marked decreases in the density(P < 0.01, P < 0.05) and total number of Spinophilin+ dendritic spines(P < 0.05). Conclusion Stereotaxic injection of AAV-mediated LINGO-1 overexpression specifically upregulates LINGO-1 in the hippocampus of mice. Abnormally high expression of LINGO-1 in the hippocampus leads to decreased hippocampal volume and loss of Spinophilin+ dendritic spines, as well as impaires spatial learning and memory abilities of mice to a certain extent.

Keywords

• lingo-1
• dendritic spine
• synapses
• hippocampus
• learning
• memory