Phen mitigates mTBI-induced loss of pre- and post synaptic elements in WT and APP/PSEN1 mice.
(A) Postsynaptic density protein 95 (PSD-95): mTBI induced a loss of PSD-95+ dendritic spines across all analyzed areas in WT mice, and in hippocampus of AD mice, as compared to the sham (CTRL) group. By contrast, Phen treated mTBI mice were not statistically different from the sham (CTRL) group. WT mTBI mice treated with Phen (2.5 and 5 mg/kg) possessed a greater number of PSD-95+ dendritic spines across both hippocampus and cortex, as compared to the mTBI vehicle group. Representative images showing PSD-95+ spines (green) in MAP2+ dendrites. Data are expressed as number of PSD-95+ dendritic spines/μm.
(B) Synaptophysin: the total volume occupied by the presynaptic marker synaptophysin IR was evaluated across WT and APP/PSEN1 mice and found to be significantly reduced in the mTBI vehicle group, as compared to their respective sham (CTRL) group. In contrast, mTBI Phen treated mice had synaptophysin IR levels no different from sham (CTRL) mice. Importantly, Phen treatment of mTBI-challenged mice resulted in significantly higher amounts of synaptophysin IR, compared to the mTBI vehicle group, across all analyzed brain areas in both WT and AD mice. *p < .05, **p < .01, ****p < .0001 vs. CTRL by Tukey’s post hoc test; ^p < .05, ^^p < .01, ^^^^p < .0001 vs. mTBI by Tukey’s post hoc test. ##p < .01 vs. CTRL by Mann-Whitney rank test. Data shown as mean ± S.E.M. @@p < .01 vs. mTBI by Mann-Whitney rank test. Data shown as mean ± S.E.M. Scale bar = 20 μm.