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.

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.

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).

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.

To investigate the effect of running exercise on depression-like behaviors in chronic unpredictable stress（CUS）-induced depression mice and GABAergic interneurons, PV⁺ interneurons and ratio of GAD67⁺/PV⁺ cells in medial prefrontal cortex（mPFC）.

After mouse model of depression was successfully established through CUS, these male C57BL/6 mice aged 4~6 weeks were randomly divided into control group, CUS control group and CUS+running group according to the results of sucrose preference test. The behaviors of the 3 groups were evaluated with sucrose preference test, forced swimming test and tail suspension test. The mRNA expression levels of GAD1, GAD2, PV and CCK in mPFC of mice were detected using qRT-PCR. The number of GABAergic interneurons and PV⁺ interneurons in mPFC of mice were quantified using immunohistochemical assay and unbiased stereological technique, and the ratio of PV⁺/GAD67⁺ cells was calculated.

Compared with those in CUS control group, the mice from the CUS+running and control groups showed a significantly higher percentage of sucrose preference（P<0.05）, shorter forced swimming immobility time（P<0.05）, and decreased tail suspension immobility time（P<0.05）. There were no obvious differences in mRNA expression levels of GAD1, GAD2 and CCK and number of GABAergic interneurons in mPFC in the 3 groups（P>0.05）. The mRNA level of PV, number of PV⁺ interneurons and ratio of PV⁺/GAD67⁺ cells in mPFC were remarkably lower in the CUS group than the CUS +running group and control group（P<0.05）.

Running exercise may exert anti-depressive effects through regulating the number and gene expression of PV⁺ interneurons.

To investigate the effects of running on the volume change of medial prefrontal cortex (mPFC), as well as amyloid beta protein (Aβ) and microglia in mPFC in mouse model of Alzheimer's disease (AD).

Male APP/PS1 transgenic AD mice aged 10 months were randomly divided into AD running group (AD Run, given active running intervention for 4 months) and AD control group (AD Ctrl), while non-transgenic mice at the same age were set as normal control group (Ctrl). The mice from the AD Ctrl and Ctrl groups received no treatment. Morris water maze test was used to evaluate the abilities of spatial learning and memory of mice, and Y maze test was adopted to assess the working memory and reference memory in the mice. The volume of mPFC and the total number of microglia (IBA1⁺ cells) in the mPFC were quantified with stereological methods. The number of activated microglia (CD68⁺/IBA1⁺ cells) in the mPFC, cell body area, and process number of microglia, number and area of Aβ plaques, and area of Aβ plaques in IBA1⁺ microglia were quantitatively measured by immunofluorescence multiple labeling and laser confocal microscopy, and the ratio of area of Aβ plaques in IBA1⁺ microglia to the total area of Aβ plaques was calculated.

The AD Run group and Ctrl group performed better than the AD Ctrl group in Morris water maze and Y maze tests. The volume of mPFC was significantly less in the AD Ctrl group than the Ctrl group (P<0.05), while that of the AD Run group was obviously larger than that of the AD Ctrl (P<0.01). The AD Ctrl group had greatly larger numbers of IBA1⁺ cells and CD68⁺/IBA1⁺ cells in the mPFC than the Ctrl group (P<0.05), whereas the AD Run group had much larger numbers of those cells than the AD Ctrl group (P<0.05). The total and average area of Aβ plaques in the mPFC was greatly diminished in the AD Run group than the AD Ctrl group (P<0.05). In addition, the AD Run group also presented larger numbers of IBA1⁺ cells and CD68⁺/IBA1⁺ cells around Aβ, larger average body area of single microglia and CD68⁺/IBA1⁺ cells, and elevated area of Aβ plaques in IBA1⁺ cells, along with its ratio to the total area of Aβ plaques in mPFC improved (P<0.05).

Running exercise increases the number of CD68⁺ microglia in the mPFC, reduces the Aβ plaques, delays the atrophy of mPFC, and thus improves the spatial learning and memory abilities as well as working memory and reference memory in APP/PS1 transgenic AD mice.