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Background/Aims: To investigate the effect of singing training on the cognitive function in Alzheimer's disease (AD) patients. Methods: Ten AD patients (mean age 78.1 years) participated in music therapy using singing training once a week for 6 months (music therapy group). Each session was performed with professional musicians using karaoke and a unique voice training method (the YUBA Method). Before and after the intervention period, each patient was assessed by neuropsychological batteries, and functional magnetic resonance imaging (fMRI) was performed while the patients sang familiar songs with a karaoke device. As the control group, another 10 AD patients were recruited (mean age 77.0 years), and neuropsychological assessments were performed twice with an interval of 6 months. Results: In the music therapy group, the time for completion of the Japanese Raven's Colored Progressive Matrices was significantly reduced (p = 0.026), and the results obtained from interviewing the patients' caregivers revealed a significant decrease in the Neuropsychiatric Inventory score (p = 0.042) and a prolongation of the patients' sleep time (p = 0.039). The fMRI study revealed increased activity in the right angular gyrus and the left lingual gyrus in the before-minus-after subtraction analysis of the music therapy intervention. Conclusion: Music therapy intervention using singing training may be useful for dementia patients by improving the neural efficacy of cognitive processing.

Motor skill training induces structural plasticity at dendritic spines in the primary motor cortex (M1). To further analyze both synaptic and intrinsic plasticity in the layer II/III area of M1, we subjected rats to a rotor rod test and then prepared acute brain slices. Motor skill consistently improved within 2 days of training. Voltage clamp analysis showed significantly higher α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate (AMPA/NMDA) ratios and miniature EPSC amplitudes in 1-day trained rats compared with untrained rats, suggesting increased postsynaptic AMPA receptors in the early phase of motor learning. Compared with untrained controls, 2-days trained rats showed significantly higher miniature EPSC amplitude and frequency. Paired-pulse analysis further demonstrated lower rates in 2-days trained rats, suggesting increased presynaptic glutamate release during the late phase of learning. One-day trained rats showed decreased miniature IPSC frequency and increased paired-pulse analysis of evoked IPSC, suggesting a transient decrease in presynaptic γ-aminobutyric acid (GABA) release. Moreover, current clamp analysis revealed lower resting membrane potential, higher spike threshold, and deeper afterhyperpolarization in 1-day trained rats—while 2-days trained rats showed higher membrane potential, suggesting dynamic changes in intrinsic properties. Our present results indicate dynamic changes in glutamatergic, GABAergic, and intrinsic plasticity in M1 layer II/III neurons after the motor training.

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BackgroundPhysical exercise has positive effects on cognitive function in elderly people. It is unknown, however, if combinations of non-pharmaceutical interventions can produce more benefits than single ones. This study aimed to identify if physical exercise combined with music improves cognitive function in normal elderly people more than exercise alone.MethodsWe enrolled 119 subjects (age 65–84 years old). Forty subjects performed physical exercise (once a week for an hour with professional trainers) with musical accompaniment (ExM group), developed by YAMAHA Music Foundation; 40 subjects performed the same exercise without music (Ex group); 39 subjects were the control group (Cont group). Before and after the year-long intervention, each patient was assessed by neuropsychological batteries. MRIs were performed before and after intervention; the Voxel-based Specific Regional analysis system for Alzheimer's Disease (VSRAD) was used to assess medial temporal lobe atrophy.ResultsAnalysis of variance (ANOVA) was significant only in visuospatial function. The multiple comparison (ExM vs. Ex, ExM vs. Cont, Ex vs. Cont) was significant between the ExM and Cont group. Intra-group analyses before and after intervention revealed significant improvement in visuospatial function in the ExM group, and significant improvements in other batteries in all three groups. The VSRAD score significantly worsened in the ExM and Ex groups.ConclusionsPhysical exercise combined with music produced more positive effects on cognitive function in elderly people than exercise alone. We attributed this improvement to the multifaceted nature of combining physical exercise with music, which can act simultaneously as both cognitive and physical training.Trial RegistrationUMIN Clinical Trials Registry (UMIN-CTR) UMIN000012148

Fatty acid binding protein 7 (FABP7) expressed by astrocytes in developing and mature brains is involved in uptake and transportation of fatty acids, signal transduction, and gene transcription. Fabp7 knockout (Fabp7 KO) mice show behavioral phenotypes reminiscent of human neuropsychiatric disorders such as schizophrenia. However, direct evidence showing how FABP7 deficiency in astrocytes leads to altered brain function is lacking. Here, we examined neuronal dendritic morphology and synaptic plasticity in medial prefrontal cortex (mPFC) of Fabp7 KO mice and in primary cortical neuronal cultures. Golgi staining of cortical pyramidal neurons in Fabp7 KO mice revealed aberrant dendritic morphology and decreased spine density compared with those in wild-type (WT) mice. Aberrant dendritic morphology was also observed in primary cortical neurons co-cultured with FABP7-deficient astrocytes and neurons cultured in Fabp7 KO astrocyte-conditioned medium. Excitatory synapse number was decreased in mPFC of Fabp7 KO mice and in neurons co-cultured with Fabp7 KO astrocytes. Accordingly, whole-cell voltage-clamp recording in brain slices from pyramidal cells in the mPFC showed that both amplitude and frequency of action potential-independent miniature excitatory postsynaptic currents (mEPSCs) were decreased in Fabp7 KO mice. Moreover, transplantation of WT astrocytes into the mPFC of Fabp7 KO mice partially attenuated behavioral impairments. Collectively, these results suggest that astrocytic FABP7 is important for dendritic arbor growth, neuronal excitatory synapse formation, and synaptic transmission, and provide new insights linking FABP7, lipid homeostasis, and neuropsychiatric disorders, leading to novel therapeutic interventions.

ExM produced greater positive effects on cognitive function and ADLs in patients with mild to moderate dementia than CS, excluding memory. Optimal interventions for dementia will likely be achieved by combining ExMand CS.

AD, Alzheimer's disease; FAST, Functional Assessment Staging; 2D-DIGE, two-dimensional differential gel electrophoresis; MALDI-TOF/TOF/MS, matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry; CSF, cerebrospinal fluid; Aβ, amyloid beta; MMSE, Mini Mental State Examination; MRI, magnetic resonance imaging; NINCDS-ADRDA, National Institute for Neurological Diseases and Stroke/Alzheimer's Disease and Related Disorders Association; CHAPS, 3-((3-cholamidopropyl) dimethylammonio)-1-propanesulfonate; DTT, dithiothreitol; SDS-PAGE, SDS-polyacrylamide gel electrophoresis; DIA, differential in-gel analysis; BVA, biological variation analysis; CBB, Coomassie brilliant blue; 2DE, two-dimensional gel electrophoresis; TFA, trifluoroacetic acid; ACTH, adrenocorticotropic hormone; Apo A-1, apolipoprotein A-1; AHSG, alpha-2-HS-glycoprotein; Apo A-4, apolipoprotein A-4; MCI, mild cognitive impairment.