A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT2AR) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but ...could be linked to increased synaptogenesis and down-regulation of cerebral 5-HT2AR. Here, we investigate if a single psychedelic dose of psilocybin changes synaptic vesicle protein 2A (SV2A) and 5-HT2AR density in the pig brain. Twenty-four awake pigs received either 0.08 mg/kg psilocybin or saline intravenously. Twelve pigs (n = 6/intervention) were euthanized one day post-injection, while the remaining twelve pigs were euthanized seven days post-injection (n = 6/intervention). We performed autoradiography on hippocampus and prefrontal cortex (PFC) sections with 3HUCB-J (SV2A), 3HMDL100907 (5-HT2AR antagonist) and 3HCimbi-36 (5-HT2AR agonist). One day post psilocybin injection, we observed 4.42% higher hippocampal SV2A density and lowered hippocampal and PFC 5-HT2AR density (−15.21% to −50.19%). These differences were statistically significant in the hippocampus for all radioligands and in the PFC for 3HCimbi-36 only. Seven days post-intervention, there was still significantly higher SV2A density in the hippocampus (+9.24%) and the PFC (+6.10%), whereas there were no longer any differences in 5-HT2AR density. Our findings suggest that psilocybin causes increased persistent synaptogenesis and an acute decrease in 5-HT2AR density, which may play a role in psilocybin’s antidepressive effects.
•Dance provides a unique model for investigating how brain integrates movement and sound.•Dancing can strengthen the connectivity between both cerebral hemispheres.•Complex movements of dancing ...recruit different motor, somatosensory and cognitive brain areas.•Long-term dance practice positively affects brain activity.•Dance practice modifies white and gray matter in various brain regions.
We conducted a systematic review of randomized clinical trials to investigate whether dance practice promotes neuroplasticity. We also determined how dancing is able to alter (1) brain volumes and structures (2) brain function, (3) psychomotor adjustment and (4) levels of neurotrophic factors. This systematic review formulated a research question based on PICO, according to the guidelines for systematic reviews and meta-analyzes (PRISMA), “What is the influence of dance practice on neuroplasticity in already mature brains?” We screened 1071 studies and from these eight studies were included in the review. Of the selected studies, all demonstrated positive structural and/or functional changes. Structural changes included increased hippocampal volume, gray matter volume in the left precentral and parahippocampal gyrus, and white matter integrity. Functional changes included alterations in cognitive function such as significant improvement in memory, attention, body balance, psychosocial parameters and altered peripheral neurotrophic factor. Based on the evidence, dance practice integrates brain areas to improve neuroplasticity.
Background:
It is necessary to seek alternative therapies for depression, because side effects of medications lead to poor adherence and some patients do not achieve a clinical treatment effect. ...Recently the role of exercise as a low-cost and easy-to-use treatment for depression has gained attention with a number of studies showing that exercise is effective at reducing depressive symptoms and improving body functions such as cardiorespiratory system and cognitive function. Because of the heterogeneity of exercise therapy programs, there is no standardized and unified program. Few studies have summarized the specific properties of exercise programs (type, intensity, duration, and frequency) and clinical prescriptions for exercise are not mentioned in most articles.
Aims:
This study aimed to investigate the feasibility and efficacy of exercise therapy for patients with depression, in order to appraise the evidence and outline accepted guidelines to direct individualized treatment plans for patients with depression based on their individual situations.
Methods:
A systematic review of English language literature including papers published from 2010 to present in PubMed was performed. Given the feasibility of prescribing exercise therapy for patients with depression, nearly 3 years of clinical studies on the treatments of depressive symptoms with exercise were first reviewed, comparing the exercise programs utilized.
Conclusions:
Exercise has therapeutic effects on depression in all age groups (mostly 18–65 years old), as a single therapy, an adjuvant therapy, or a combination therapy, and the benefits of exercise therapy are comparable to traditional treatments for depression. Moderate intensity exercise is enough to reduce depressive symptoms, but higher-dose exercise is better for overall functioning. Exercise therapy has become more widely used because of its benefits to the cardiovascular system, emotional state, and systemic functions.
Recommendations:
Aerobic exercise/mind-body exercise (3–5 sessions per week with moderate intensity lasting for 4–16 weeks) is recommended. Individualized protocols in the form of group exercise with supervision are effective at increasing adherence to treatment.
Morphological differences in the auditory brain of musicians compared to nonmusicians are often associated with life‐long musical activity. Cross‐sectional studies, however, do not allow for any ...causal inferences, and most experimental studies testing music‐driven adaptations investigated children. Although the importance of the age at which musical training begins is widely recognized to impact neuroplasticity, there have been few longitudinal studies examining music‐related changes in the brains of older adults. Using magnetic resonance imaging, we measured cortical thickness (CT) of 12 auditory‐related regions of interest before and after 6 months of musical instruction in 134 healthy, right‐handed, normal‐hearing, musically‐naive older adults (64–76 years old). Prior to the study, all participants were randomly assigned to either piano training or to a musical culture/music listening group. In five regions—left Heschl's gyrus, left planum polare, bilateral superior temporal sulcus, and right Heschl's sulcus—we found an increase in CT in the piano training group compared with the musical culture group. Furthermore, CT of the right Heschl's gyrus could be identified as a morphological substrate supporting speech in noise perception. The results support the conclusion that playing an instrument is an effective stimulator for cortical plasticity, even in older adults.
Using magnetic resonance imaging (MRI), we measured cortical thickness of 12 auditory‐related regions of interest before and after six months of musical instruction in 134 healthy, right‐handed, normal‐hearing, musically naive older adults. The results support the conclusion that playing an instrument is an effective stimulator for cortical plasticity, even in older adults.
'Enriched environments' are a key experimental paradigm to decipher how interactions between genes and environment change the structure and function of the brain across the lifespan of an animal. The ...regulation of adult hippocampal neurogenesis by environmental enrichment is a prime example of this complex interaction. As each animal in an enriched environment will have a slightly different set of experiences that results in downstream differences between individuals, enrichment can be considered not only as an external source of rich stimuli but also to provide the room for individual behaviour that shapes individual patterns of brain plasticity and thus function.
Gross‐motor impairments are common after stroke, but efficacious and motivating therapies for these impairments are scarce. We present a novel musical sonification therapy especially designed to ...retrain gross‐motor functions. Four stroke patients were included in a clinical pre–post feasibility study and were trained with our sonification training. Patients’ upper‐extremity functions and their psychological states were assessed before and after training. The four patients were subdivided into two groups, with both groups receiving 9 days of musical sonification therapy (music group, MG) or a sham sonification training (control group, CG). The only difference between these training protocols was that, in the CG, no sound was played back. During the training the patients initially explored the acoustic effects of their arm movements, and at the end of the training the patients played simple melodies by moving their arms. The two patients in the MG improved in nearly all motor function tests after the training. They also reported in the stroke impact scale, which assesses well‐being, memory, thinking, and social participation, to be less impaired by the stroke. The two patients in the CG did benefit less from the movement training. Taken together, musical sonification may be a promising therapy for impairments after stroke.
Psychedelics have inspired new hope for treating brain disorders, as they seem to be unlike any treatments currently available. Not only do they produce sustained therapeutic effects following a ...single administration, they also appear to have broad therapeutic potential, demonstrating efficacy for treating depression, post-traumatic stress disorder (PTSD), anxiety disorders, substance abuse disorder, and alcohol use disorder, among others. Psychedelics belong to a more general class of compounds known as psychoplastogens, which robustly promote structural and functional neural plasticity in key circuits relevant to brain health. Here we discuss the importance of structural plasticity in the treatment of neuropsychiatric diseases, as well as the evidence demonstrating that psychedelics are among the most effective chemical modulators of neural plasticity studied to date. Furthermore, we provide a theoretical framework with the potential to explain why psychedelic compounds produce long-lasting therapeutic effects across a wide range of brain disorders. Despite their promise as broadly efficacious neurotherapeutics, there are several issues associated with psychedelic-based medicines that drastically limit their clinical scalability. We discuss these challenges and how they might be overcome through the development of non-hallucinogenic psychoplastogens. The clinical use of psychedelics and other psychoplastogenic compounds marks a paradigm shift in neuropsychiatry toward therapeutic approaches relying on the selective modulation of neural circuits with small molecule drugs. Psychoplastogen research brings us one step closer to actually curing mental illness by rectifying the underlying pathophysiology of disorders like depression, moving beyond simply treating disease symptoms. However, determining how to most effectively deploy psychoplastogenic medicines at scale will be an important consideration as the field moves forward.
Electroconvulsive shocks (ECS) and ketamine are antidepressant treatments with a relatively fast onset of therapeutic effects compared to conventional medication and psychotherapy. While the exact ...neurobiological mechanisms underlying the antidepressant response of ECS and ketamine are unknown, both interventions are associated with neuroplasticity. Restoration of neuroplasticity may be a shared mechanism underlying the antidepressant efficacy of these interventions. In this systematic review, literature of animal models of depression is summarized to examine the possible role of neuroplasticity in ECS and ketamine on a molecular, neuronal, synaptic and functional level, and specifically to what extent these mechanisms are shared between both interventions. The results highlight that hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) levels are consistently increased after ECS and ketamine. Moreover, both interventions positively affect glutamatergic neurotransmission, astrocyte and neuronal morphology, synaptic density, vasculature and functional plasticity. However, a small number of studies investigated these processes after ECS. Understanding the shared fundamental mechanisms of fast-acting antidepressants can contribute to the development of novel therapeutic approaches for patients with severe depression.
•Hippocampal neurogenesis and BDNF are central outcomes of ECS and ketamine.•ECS and ketamine affected several neuroplastic levels, e.g. astrocytes, LTP.•Glutamatergic neurotransmission is involved in their mode of action.•ECS and ketamine have a largely shared underlying neurobiological mechanism.
BACKGROUND: Diverse antidepressants were recently described to bind to TrkB and drive a positive allosteric modulation of endogenous BDNF. Although neurotrophins such as BDNF can bind to the p75 ...neurotrophin receptor (p75NTR), their precursors are the high affinity p75NTR ligands. While part of an unrelated receptor family capable of inducing completely opposite physiological changes, TrkB and p75NTR feature a cross-like conformation dimer and carry a cholesterol-recognition and alignment consensus in the transmembrane domain. Since such qualities were found crucial for antidepressants to bind to TrkB and drive behavioral and neuroplasticity effects, we hypothesized that their effects might also depend on p75NTR. METHODS: ELISA-based binding assay and NMR spectroscopy were accomplished to assess whether antidepressants would bind to p75NTR. HEK293T cells and a variety of in vitro assays were used to address whether fluoxetine (FLX) or ketamine (KET) would trigger any α- and γ-secretase-dependent p75NTR proteolysis, and lead to p75NTR nuclear localization. Ocular dominance shift was performed with male and female p75KO mice to study the effects of KET and FLX on brain plasticity, in addition to pharmacological interventions to verifying how p75NTR signaling is important for the effects of KET and FLX in enhancing extinction memory in male WT mice and rats. RESULTS: Antidepressants were found binding to p75NTR, FLX and KET triggered the p75NTR proteolytic pathway and induced p75NTR-dependent behavioral/neuroplasticity changes. CONCLUSION: We thus hypothesize that antidepressants co-opt both BDNF/TrkB and proBDNF/p75NTR systems to induce a more efficient activity-dependent synaptic competition, thereby boosting the brain ability for remodeling.
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