ABSTRACT
MicroRNA (miR)-34a was recently determined to contribute to the pathological development of Alzheimer's disease (AD). miR-34a deficiency significantly attenuates cognitive deficits in amyloid precursor protein (APP)/presenilin 1 (PS1) mice; however, its role in early AD pathology and the underlying mechanisms remain elusive. Here, we confirmed that the increase of miR-34a expression in APP/PS1 mice was earlier than the relevant AD pathological characteristics, such as amyloid-ß production, amyloid plaque deposition, and cognitive deficits. Furthermore, because predicted miR-34a target genes were broadly linked to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors, we evaluated synaptic plasticity by investigating high-frequency conditioning tetanus-induced excitatory postsynaptic potential, which revealed that synaptic plasticity was promoted in miR-34a knockout/APP/PS1 mice. Therefore, we assessed the expression of the presynaptic components synaptophysin and postsynaptic density protein 95 (PSD95) and found that synaptophysin and PSD95 were not altered by miR-34a deficiency. Additionally, the synaptic strength (vesicular fusion, vesicular docking, and transporting) was either not significantly changed. We also evaluated the levels of AMPA and NMDA receptors, which showed that the expression of AMPA and NMDA receptors was markedly upregulated in APP/PS1 mice with miR-34a deficiency. We conclude that miR-34a is involved in synaptic deficits in AD pathological development, which was, at least in part, due to the inhibition of NMDA (by miR-34a-5p) and AMPA (by miR-34a-3p) receptor expression.
Subject(s)
Brain/metabolism , Cognition/physiology , Maze Learning/physiology , MicroRNAs/genetics , Neuronal Plasticity/physiology , Receptors, AMPA/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Amyloid beta-Peptides/blood , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Animals , Disease Models, Animal , Mice , Mice, Transgenic , MicroRNAs/metabolism , Presenilin-1/genetics , Presenilin-1/metabolismABSTRACT
OBJECTIVE: This study explores the efficacy and safety of computer-assisted stereotactic transplantation of human retinal pigment epithelium (hRPE) cells in the treatment of Parkinson disease (PD). METHODS: Guided by computed tomography and magnetic resonance imaging image mergence, we transplanted 4 × 10 hRPE cells into the putamina and lateral ventricles of 17 PD cases by stereotactic surgery. The transplantation site was located in the contralateral side of the symptoms and signs. RESULTS: At 3 months after operation, the effective rates of cell transplantation were 82.4% in the contralateral site and 64.7% in the ipsilateral site. Minority of the cases had mild dizziness and hemiparesis, but the durations were short. CONCLUSIONS: Computer-assisted stereotactic transplantation of hRPE for the treatment of PD is safe and efficient.
