Summary
Experience
has shown that therapy using music for therapeutic purposes has certain
effects on neuropsychiatric disorders (both functional and organic
disorders). However, the mechanisms of action underlying music therapy
remain unknown, and scientific clarification has not advanced.
While
that study disproved the Mozart effect, the effects of music on the
human body and mind were not disproved. In fact, more scientific studies
on music have been conducted in recent years, mainly in the field of
neuroscience, and the level of interest among researchers is increasing.
The results of past studies have clarified that music influences and
affects cranial nerves in humans from fetus to adult. The effects of
music at a cellular level have not been clarified, and the mechanisms of
action for the effects of music on the brain have not been elucidated.
We
propose that listening to music facilitates the neurogenesis, the
regeneration and repair of cerebral nerves by adjusting the secretion of
steroid hormones, ultimately leading to cerebral plasticity. Music
affects levels of such steroids as cortisol (C), testosterone (T) and
estrogen (E), and we believe that music also affects the receptor genes
related to these substances, and related proteins.
In the
prevention of Alzheimer’s disease and dementia, hormone replacement
therapy has been shown to be effective, but at the same time, side
effects have been documented, and the clinical application of hormone
replacement therapy is facing a serious challenge. Conversely, music is
noninvasive, and its existence is universal and mundane. Thus, if music
can be used in medical care, the application of such a safe and
inexpensive therapeutic option is limitless.
Introduction
In
the history of mankind, music and medicine have always maintained a
close relationship. This remains true with hunter-gatherer cultures that
are thought to reflect primitive human forms as clarified by cultural
anthropological and ethnomusicological studies. Interestingly, music has
been used for the treatment of neuropsychiatric disorders in
hunter-gatherer cultures.
However,
in westernized societies in the 21st Century, no established therapy
exists for neuropsychiatric disorders such as stress disorders, mood
disorders (depression) and dementia. Experience has shown that therapy
using music for therapeutic purposes has certain effects on
neuropsychiatric disorders (both functional and organic disorders), and
music therapy is currently being administered mainly in the United
States and Europe in clinical and welfare settings. However, the
mechanisms of action underlying music therapy remain unknown, and
scientific clarification has not advanced.
Various studies have examined the effects of listening to music on the brain [1] and [2]. The study by Rauscher et al. [3]
on the Mozart effect is one of the most famous studies and has had both
positive and negative impacts on music therapy and music education,
since the article was published, it received a lot of attention.
However, many subsequent studies have questioned the reliability of the
results, and Chabris et al. [4]
also published a study disproving the Mozart effect. While that study
disproved the Mozart effect, the effects of music on the human body and
mind were not disproved. In fact, more scientific studies on music have
been conducted in recent years, mainly in the field of neuroscience, and
the level of interest among researchers is increasing [5] and [6]. The results of past studies have clarified that music influences and affects cranial nerves in humans from fetus to adult [7].
The
most important discovery by such studies has been that music enhances
synaptic plasticity in the brain. In other words, studies comparing
musicians and non-musicians and music learners and non-learners have
clarified that music brings about cerebral plasticity. Music affects
neuronal learning and readjustment (response of brain cells to sound and
music stimuli, and changes in cell counts), and this effect lasts for a
long period of time [7].
For example, even when neurodegenerative diseases such as Alzheimer’s
disease causes memory loss, patients can still remember music from the
past, and listening to music can facilitate the recovery of other
memories. Music listening during the early post- stroke stage can
enhance cognitive recovery and prevent negative mood [8].
This
type of memory recovery is accompanied by the reconfiguration of
existing neuron networks, and it may allow access to long-term memory.
However, most past studies have been based on brain imaging modalities
such as positron emission tomography (PET) or functional magnetic
resonance imaging (fMRI). The effects of music at a cellular level have
not been clarified, and the mechanisms of action for the effects of
music on the brain have not been elucidated.
Hypothesis
We
propose herein that listening to music facilitates the neurogenesis,
the regeneration and repair of neurons by adjusting the secretion of
steroid hormones in both directions (increase and decrease), ultimately
leading to cerebral plasticity. Music affects levels of such steroids as
cortisol (C), testosterone (T) and estrogen (E), and we believe that
music also affects the receptor genes related to these substances, and
related proteins.
Evaluation of the hypothesis
Plastic
effects of steroids on the brain have been documented in many animal
species. For example, vocal communication is a common characteristic
among many vertebrates, and steroid hormones are closely involved in the
formation of neural mechanism for vocal behaviors in fish, amphibians,
birds and mammals (including primates) [9].
In anurans, androgen and E are involved in the expression of vocal
behaviors by controlling vocal organ formation, advertisement calling
and release calling [10].
The most well-known relationship between steroids and cerebral
plasticity is vocal (singing) behaviors in birds. The development of
vocal behaviors in singing birds involves complicated processes
including neurons and muscles, and steroid hormones (T and E) are
involved during many steps, such as neuron organization, neuron survival
and neural song-system formation [11] and [12].
The
relationship between steroids and cerebral plasticity has been
confirmed in humans. It is well known that the nervous system is a
target for steroids (peripheral glands and neurosteroids which are
synthesized by nerve cells). Even if those steroids varies its origin,
both are neuroactive [13].
They regulate important functions such as reproduction, feeding
behavior, brain development, neurogenesis, neuroprotection, cognition
and memory [14] and [15]. Particularly, trophic and neuroprotective functions of steroids have recently attracted a great deal of attention [16], [17], [18], [19], [20], [21], [22], [23] and [24].
For example, corticosteroid (C) is a substance that modifies stress in
many ways, and while C acts on the hippocampus (for long-term
potentiation (LTP)), amygdaloid complex and frontal lobe, high levels of
C damage neurons. E and T are also involved with the expression,
regeneration, repair and protection of nerve cells via gene expression
regulation and non-genomic circuits. Within the genomic system, E is
involved with the regulation of brain-derived neurotrophic factor (BDNF)
and nerve growth factor (NGF), and within the non-genomic system, E is
involved with nerve signal transmission and amyloid beta suppression [25], [26], [27], [28], [29] and [30]. T also elevates NGF and p75-nerve growth factor receptors to decrease amyloid beta [31] and [32].
In
humans, primates, rodents and birds, steroids (C, T and E) influence
cognitive abilities (spatial perception and cognition; visual (object
recognition) and spatial memory (object placement and radial arm maze)).
Particularly in birds, steroids (17beta-estradiol (E2)) improve spatial
cognition (memory) [33] and [34].
In rats and mice, many studies have reported that steroid hormones
improve spatial perception and cognition (learning and memory) [35] and [36].
In
humans, steroid hormones are involved in spatial perception and
cognition. The relationship between T and cognitive abilities is
negative in men and positive in women [37], [38], [39], [40], [41] and [42]. In women, the balance of T and E associated with the menstrual cycle alters cognitive abilities [41] and [43].
Furthermore, in women, age-related decreases in E are thought to be
involved in cognitive dysfunction, memory disorder, learning disorder,
depression and mood disorder. Numerous studies have also examined the
relationship between E and Alzheimer’s disease accompanying marked
cognitive dysfunction. The level of E is lower for Alzheimer patients
than for healthy individuals, and this decrease in E may hasten the
progression of Alzheimer’s disease and facilitate amyloid beta
accumulation, which is one of the causes of characteristic disorders
such as memory disorders. Tissue experiments using test tubes and
postmortem brains have shown that E suppresses amyloid beta elevation
and deposition to prevent nerve cell damage [44], [45], [46] and [47]. Moreover, T administration to elderly men reportedly improves cognitive function [48].
The correlation between musical ability and spatial cognition has long been known [49], [50] and [51].
Many studies have investigated the relationship of musical ability to
spatial perception and cognition in humans. The assumption that some
correlation exists between musical ability and steroid hormones also
appears reasonable. In fact, Hassler discovered that the relationship
between T and musical ability (music composition) resembled that between
T and other forms of spatial perception and cognition [50] and [52].
Furthermore,
the relationship between music and steroid hormones is not limited to
musical ability. In the field of behavioral endocrinology and
neuroendocrinology, many studies have documented that musical
stimulation (listening) affects various biochemical substances [53], [54] and [55].
In particular, many studies based findings on C. Experience has shown
that listening to music is effective in alleviating and reliving stress.
In many studies, stress reduction due to music listening has been
attributed to reductions in C [56] and [57]. Listening to music also reportedly alters levels of T (increase and decrease) [58] and [59].
The research reported that musical activities (listening and playing)
adjust steroid secretion in elderly individuals and are likely to
alleviate psychological states such as anxiety and tension. Furthermore,
levels of steroids changed in both directions, increasing in subjects
with low hormone levels and decreasing in subjects with high hormone
levels [60].
Conclusion
Music
listening and playing altered steroid levels agrees with the results of
various previous studies that have documented strong correlations
between steroids and spatial perception and cognition and the effects of
music listening on steroid secretion. Summarizing these results, the
hypothesis that listening to music adjusts the steroid hormone cascade
and facilitating the neurogenesis, regeneration and repair of neuron
appears highly plausible. At this point, the effects of music on
steroids are unclear, but music appears to be involved with steroid
production via the pathway from the auditory system to the auditory
area, particularly the neural pathway (emotion circuits) mediated by the
cerebral limbic system (hypothalamic-pituitary-adrenal axis and
amygdaloid complex).
In recent
years, the possible involvement of nerve damage in neuropsychiatric
disorders has been suggested, and musical activities may enable the
protection, repair and even regeneration of human cerebral nerves. In
the prevention of Alzheimer’s disease and dementia, hormone replacement
therapy has been shown to be effective [46] and [61],
but at the same time, side effects have been documented, and the
clinical application of hormone replacement therapy is facing a serious
challenge [62].
Conversely, music is noninvasive, and its existence is universal and
mundane. Thus, if music can be used in medical care, the application of
such a safe and inexpensive therapeutic option is limitless.
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