Music with Different Tones Affects the Development of Brain Nerves in Mice in Early Life through BDNF and Its Downstream Pathways

Abstract

As a means of environmental enrichment, music environment has positive and beneficial effects on biological neural development. Kunming white mice (61 days old) were randomly divided into the control group (group C), the group of D-tone (group D), the group of A-tone (group A) and the group of G-tone (group G). They were given different tonal music stimulation (group A) for 14 consecutive days (2 h/day) to study the effects of tonal music on the neural development of the hippocampus and prefrontal cortex of mice in early life and its molecular mechanisms. The results showed that the number of neurons in the hippocampus and prefrontal cortex of mice increased, with the cell morphology relatively intact. In addition, the number of dendritic spines and the number of dendritic spines per unit length were significantly higher than those in group C, and the expressions of synaptic plasticity proteins (SYP and PSD95) were also significantly elevated over those in group C. Compared with group C, the expression levels of BDNF, TRKB, CREB, PI3K, AKT, GS3Kβ, PLCγ1, PKC, DAG, ERK and MAPK genes and proteins in the hippocampus and prefrontal cortex of mice in the music groups were up-regulated, suggesting that different tones of music could regulate neural development through BDNF and its downstream pathways. The enrichment environment of D-tone music is the most suitable tone for promoting the development of brain nerves in early-life mice. Our study provides a basis for screening the optimal tone of neuroplasticity in early-life mice and for the treatment of neurobiology and neurodegenerative diseases.

Keywords: BDNF-downstream pathways; music; neurodevelopment; tone.

Figure 1

Effects of music in different tones on Nissl Staining. (A) In hippocampus. (B) In prefrontal cortex.

Figure 2

Effects of music in different tones on the development of neuronal dendrites. (A). In hippocampus. (B). In prefrontal cortex. Data in each group were described as Mean ± SD. (a) Results of Golgi staining in hippocampus of each group, (b) Number of dendritic spines of each group, (c) Length of dendritic spine of each group(µm), (d) The number of intersection points between dendritic spines and concentric circles in each group, (e) Total intersections of shall analysis of each group, (f) Number of intersections in shall analysis, (g,h) Dendritic spine density within 10 microns in each group. (a–d) shows that bars with different lowercase represent statistical significance between two groups (p < 0.05).

Figure 2

Effects of music in different tones on the development of neuronal dendrites. (A). In hippocampus. (B). In prefrontal cortex. Data in each group were described as Mean ± SD. (a) Results of Golgi staining in hippocampus of each group, (b) Number of dendritic spines of each group, (c) Length of dendritic spine of each group(µm), (d) The number of intersection points between dendritic spines and concentric circles in each group, (e) Total intersections of shall analysis of each group, (f) Number of intersections in shall analysis, (g,h) Dendritic spine density within 10 microns in each group. (a–d) shows that bars with different lowercase represent statistical significance between two groups (p < 0.05).

Figure 3

Effects of music in different tones on synaptic protein expression (200 μm). (A). In hippocampus. (B). In prefrontal cortex. Data in each group were described as Mean ± SD. Bars with different lowercase represent statistical significance (p < 0.05) between two groups.

Figure 3

Effects of music in different tones on synaptic protein expression (200 μm). (A). In hippocampus. (B). In prefrontal cortex. Data in each group were described as Mean ± SD. Bars with different lowercase represent statistical significance (p < 0.05) between two groups.

Figure 4

Effects of music in different tones on mRNA and protein expression levels of the BDNF/TRKB/CREB pathway. (A). In hippocampus. (B). In prefrontal cortex. (a–c) showed that the bar diagram of BDNF, TrKB and CREB genes. (d,e) showed that the bar diagram of BDNF, TrKB and CREB proteins. The different lowercase letters at the top of the bar chart indicated significant statistical differences among different groups (p < 0.05).

Figure 5

Effects of music in different tones on mRNA and protein expression levels of the PLCγ1/PKC pathway. (A). In hippocampus. (B). In prefrontal cortex. (a–c) showed that the bar diagram of PLCγ1, DAG and PKC genes. (d,e) showed that the bar diagram of PLCγ1 and PKC proteins. The different lowercase letters at the top of the bar chart indicated significant statistical differences among different groups (p < 0.05).

Figure 5

Effects of music in different tones on mRNA and protein expression levels of the PLCγ1/PKC pathway. (A). In hippocampus. (B). In prefrontal cortex. (a–c) showed that the bar diagram of PLCγ1, DAG and PKC genes. (d,e) showed that the bar diagram of PLCγ1 and PKC proteins. The different lowercase letters at the top of the bar chart indicated significant statistical differences among different groups (p < 0.05).

Figure 6

Effects of music in different tones on mRNA and protein expression levels of the PI3K/AKT pathway. (A). In hippocampus. (B). In prefrontal cortex. (a–c) showed that the bar diagram of PI3K, AKT and GS3Kβ genes. (d,e) showed that the bar diagram of PI3K and AKT proteins. The different lowercase letters at the top of the bar chart indicated significant statistically differences among different groups (p < 0.05).

Figure 7

Effects of music in different tones on mRNA and protein expression levels of the MAPK/ERK pathway. (A). In hippocampus. (B). In prefrontal cortex. (a,b) showed that the bar diagram of ERK and MAPK genes. (c,d) showed that the bar diagram of ERK and MAPK proteins. The different lowercase letters at the top of the bar chart indicated significantly statistical differences among different groups (p < 0.05).