Repeated cannabidiol treatment affects neuroplasticity and endocannabinoid signaling in the prefrontal cortex of the Flinders Sensitive Line (FSL) rat model of depression.

Delayed therapeutic responses and limited efficacy are the main challenges of existing antidepressant drugs, thereby incentivizing the search for new potential treatments. Cannabidiol (CBD), non-psychotomimetic component of cannabis, has shown promising antidepressant effects in different rodent models, but its mechanism of action remains unclear. Herein, we investigated the antidepressant-like effects of repeated CBD treatment on behavior, neuroplasticity markers and lipidomic profile in the prefrontal cortex (PFC) of Flinders Sensitive Line (FSL), a genetic animal model of depression, and their control counterparts Flinders Resistant Line (FRL) rats. Male FSL animals were treated with CBD (10 mg/kg; i.p.) or vehicle (7 days) followed by Open Field Test (OFT) and the Forced Swimming Test (FST). The PFC was analyzed by a) western blotting to assess markers of synaptic plasticity and cannabinoid signaling in synaptosome and cytosolic fractions; b) mass spectrometry-based lipidomics to investigate endocannabinoid levels (eCB). CBD attenuated the increased immobility observed in FSL, compared to FRL in FST, without changing the locomotor behavior in the OFT. In synaptosomes, CBD increased ERK1, mGluR5, and Synaptophysin, but failed to reverse the reduced CB1 and CB2 levels in FSL rats. In the cytosolic fraction, CBD increased ERK2 and decreased mGluR5 expression in FSL rats. Surprisingly, there were no significant changes in eCB levels in response to CBD treatment. These findings suggest that CBD effects in FSL animals are associated with changes in synaptic plasticity markers involving mGluR5, ERK1, ERK2, and synaptophysin signaling in the PFC, without increasing the levels of endocannabinoids in this brain region.

Design and Implementation of a Brief Digital Mindfulness and Compassion Training App for Health Care Professionals: Cluster Randomized Controlled Trial.

BACKGROUND: Several studies show that intense work schedules make health care professionals particularly vulnerable to emotional exhaustion and burnout. OBJECTIVE: In this scenario, promoting self-compassion and mindfulness may be beneficial for well-being. Notably, scalable, digital app-based methods may have the potential to enhance self-compassion and mindfulness in health care professionals. METHODS: In this study, we designed and implemented a scalable, digital app-based, brief mindfulness and compassion training program called "WellMind" for health care professionals. A total of 22 adult participants completed up to 60 sessions of WellMind training, 5-10 minutes in duration each, over 3 months. Participants completed behavioral assessments measuring self-compassion and mindfulness at baseline (preintervention), 3 months (postintervention), and 6 months (follow-up). In order to control for practice effects on the repeat assessments and calculate effect sizes, we also studied a no-contact control group of 21 health care professionals who only completed the repeated assessments but were not provided any training. Additionally, we evaluated pre- and postintervention neural activity in core brain networks using electroencephalography source imaging as an objective neurophysiological training outcome. RESULTS: Findings showed a post- versus preintervention increase in self-compassion (Cohen d=0.57; P=.007) and state-mindfulness (d=0.52; P=.02) only in the WellMind training group, with improvements in self-compassion sustained at follow-up (d=0.8; P=.01). Additionally, WellMind training durations correlated with the magnitude of improvement in self-compassion across human participants (ρ=0.52; P=.01). Training-related neurophysiological results revealed plasticity specific to the default mode network (DMN) that is implicated in mind-wandering and rumination, with DMN network suppression selectively observed at the postintervention time point in the WellMind group (d=-0.87; P=.03). We also found that improvement in self-compassion was directly related to the extent of DMN suppression (ρ=-0.368; P=.04). CONCLUSIONS: Overall, promising behavioral and neurophysiological findings from this first study demonstrate the benefits of brief digital mindfulness and compassion training for health care professionals and compel the scale-up of the digital intervention. TRIAL REGISTRATION: Trial Registration: International Standard Randomized Controlled Trial Number Registry ISRCTN94766568, https://www.isrctn.com/ISRCTN94766568.

Current scenario and potential of music therapy in the management of diseases.

Over the preceding years, music therapy has gained tremendous attention due to new findings of music in management of various conditions like Alzheimer's, depression, anxiety, insomnia, etc. Music is a non-invasive, patient-friendly and pleasant form of therapy with minimal or no side effects. It activates the reward pathway of brain by influencing several processes such as dopamine release, reduction in cortisol levels, increase in estrogen and testosterone levels. This review article focuses on advantages and disadvantages of music therapy, mechanism of action of music in brain and its effective applications in the management of different diseases. The article covers history of music therapy in America, Egypt, and India with practice of music therapy. The advanced effects of music therapy in autism, cancer, post-operative pain, Parkinson's disease, selective mutism, stroke, heart problems, pregnancy, eating disorders, bone fractures and obsessive compulsive disorders are discussed. Also the effect of music therapy on the quality of sleep and brain waves has been discussed. This is an established profession in western countries like America, UK, Australia, and Canada, but not in low-income countries like India where it needs to be standardized.

Neuropsychological Consequences of Massive Trauma: Implications and Clinical Interventions.

Traumatic events, especially massive trauma resulting from catastrophic incidents, wars, or severe abuse can elicit significant neuropsychological alterations, with profound implications for cognitive, emotional, and behavioral functioning. This mini-review delineates the primary neural changes post-trauma and underscores the importance of timely neuropsychological and clinical interventions. Specific brain regions, including the amygdala and prefrontal cortex, undergo physiological changes that can lead to memory impairments, attention deficits, and emotional disturbances. PTSD, a commonly diagnosed condition post-trauma, exemplifies the intricate relationship between trauma and memory processing. Furthermore, the concept of neuroplasticity, the brain's inherent ability to adapt and rewire, offers hope for recovery. Current clinical interventions, such as cognitive behavioral therapy, mindfulness practices, and biofeedback, leverage this neuroplastic potential to foster healing. The review underscores the vital importance of early intervention to mitigate long-term neuropsychological impacts, emphasizing the role of timely and targeted clinical interventions. The synthesis of this knowledge is crucial for clinicians, allowing for informed therapeutic approaches that holistically address both the physiological and psychological dimensions of trauma.

[Gender differences in antidepressant effect of raw Rehmanniae Radix].

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

THE EFFECT OF REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION AND PHARMACOTHERAPY ON SERUM PROTEIN S100B IN TREATMENT-RESISTANT DEPRESSION.

BACKGROUND: Transcranial magnetic stimulation (TMS) is considered an effective and fast option for treating patients with major depressive disorder. With the increase in treatment options, the determination of biomarkers that predict which treatment will benefit patients the most has been a matter of curiosity for researchers. SUBJECTS AND METHODS: In this study, we aimed to determine the changes in serum concentrations of S100B, a neurotrophic factor thought to play a role in psychiatric disorders after repetitive TMS (rTMS) and anti-depressant drugs (AD) therapy in patients with major depressive disorder(MDD).In this cohort study, rTMS was applied to the left dorsolateral prefrontal cortex(DLPFC) of drug-resistant MDD patients, while another group of MDD patients was treated with AD for three weeks. Patients were evaluated by psychometric tests and serum S100B concentration at baseline and following intervention. There was also a healthy control group in which patients' S100B values were compared at baseline. RESULTS: There is a population with a total of 48 participants.(16 healthy controls,16 anti-depressant treatment groups, 16 individuals who received rTMS in addition to anti-depressant ) A total of 48 participants completed the study, and the S100B levels of the rTMS group and the anti-depressant drug group were found to be significantly higher than the healthy control group. S100B values, which were higher in the anti-depressant and rTMS groups compared to healthy controls, showed a significant reduction in group time interaction (start and end of treatment). CONCLUSION: rTMS of DLPFC demonstrated an effective complementary treatment for treatment-resistant patients with MDD, especially for patients with relatively high serum S100B concentrations.

Within-Person Modulation of Neural Networks following Interoceptive Awareness Training through Mindful Awareness in Body-Oriented Therapy (MABT): A Pilot Study.

Interoception, the representation of the body's internal state, is increasingly recognized for informing subjective wellbeing and promoting regulatory behavior. However, few empirical reports characterize interoceptive neural networks, and fewer demonstrate changes to these networks in response to an efficacious intervention. Using a two-group randomized controlled trial, this pilot study explored within-participant neural plasticity in interoceptive networks following Mindful Awareness in Body-oriented Therapy (MABT). Participants (N = 22) were assigned to either 8 weeks of MABT or to a no-treatment control and completed baseline and post-intervention assessments that included subjective interoceptive awareness (MAIA) and neuroimaging of an interoceptive awareness task. MABT was uniquely associated with insula deactivation, increased functional connectivity between the dorsal attention network and the somatomotor cortex, and connectivity changes correlated positively with changes in subjective interoception. Within the MABT group, changes in subjective interoception interacted with changes in a predefined anterior cingulate seed region to predict changes in right middle insula activity, a putative primary interoceptive representation region. While the small sample size requires the replication of findings, results suggest that interoceptive training enhances sensory-prefrontal connectivity, and that such changes are commensurate with enhanced interoceptive awareness.

Neuroplasticity: The Continuum of Change.

Neuroplasticity is a term that is increasingly permeating mainstream discourse and being used by the popular press to simplify descriptions of how the brain changes in response to stimuli such as exercise, sleep, food, drugs of abuse, and medicines, among others. However, it is a complex, multifaceted concept representing a continuum connecting molecular, cellular, and circuit-level changes and their effects on human behavior. In this Viewpoint, we examine neuroplasticity from several perspectives to construct a holistic view of this ambiguous term. By engaging experts across various scientific disciplines, we attempt to provide an easy entry point to the concept of neuroplasticity for readers of ACS Chemical Neuroscience. By highlighting how neuroplasticity changes in both health and disease, we demonstrate that the concept is applicable to both adaptive and maladaptive responses to stimuli, underscoring its significance in chemical neuroscience.

Brain Mitochondrial Bioenergetics in Genetic Neurodevelopmental Disorders: Focus on Down, Rett and Fragile X Syndromes.

Mitochondria, far beyond their prominent role as cellular powerhouses, are complex cellular organelles active as central metabolic hubs that are capable of integrating and controlling several signaling pathways essential for neurological processes, including neurogenesis and neuroplasticity. On the other hand, mitochondria are themselves regulated from a series of signaling proteins to achieve the best efficiency in producing energy, in establishing a network and in performing their own de novo synthesis or clearance. Dysfunctions in signaling processes that control mitochondrial biogenesis, dynamics and bioenergetics are increasingly associated with impairment in brain development and involved in a wide variety of neurodevelopmental disorders. Here, we review recent evidence proving the emerging role of mitochondria as master regulators of brain bioenergetics, highlighting their control skills in brain neurodevelopment and cognition. We analyze, from a mechanistic point of view, mitochondrial bioenergetic dysfunction as causally interrelated to the origins of typical genetic intellectual disability-related neurodevelopmental disorders, such as Down, Rett and Fragile X syndromes. Finally, we discuss whether mitochondria can become therapeutic targets to improve brain development and function from a holistic perspective.

The antidepressant-like effects of Danzhi Xiaoyao San and its active ingredients.

BACKGROUND: Depression is a severe mental illness that endangers human health. Depressed individuals are prone to sleep less and to the loss of appetite for food; their thinking and cognition processes, as well as mood, may even be affected. Danzhi Xiaoyao San (DXS), documented in the Internal Medicine Summary, has been used for hundreds of years in China and is widely applied traditionally to treat liver qi stagnation, liver and spleen blood deficiency, menstrual disorders, and spontaneous and night sweating. DXS can also clear heat and drain the liver. Presently, it is used frequently in the treatment of depression based on its ability to clear the liver and alleviate depression. PURPOSE: To summarize clinical and preclinical studies on the antidepressant-like effects of DXS, understand the material basis and mechanisms of these effects, and offer new suggestions and methods for the clinical treatment of depression. METHODS: "Danzhi Xiaoyao", "Danzhixiaoyao", "Xiaoyao", "depression" and active ingredients were entered as keywords in PubMed, Google Scholar, CNKI and WANFANG DATA databases in the search for material on DXS and its active ingredients. The PRISMA guidelines were followed in this review process. RESULTS: Per clinical reports, DXS has a therapeutic effect on patients with depression but few side effects. DXS and its active ingredients allegedly produce their neuroprotective antidepressant-like effects by modulating monoamine neurotransmitter levels, inhibiting the hypothalamic-pituitary-adrenal (HPA) axis hyperfunction, reducing neuroinflammation and increasing neurotrophic factors. CONCLUSION: Overall, DXS influences multiple potential mechanisms to exert its antidepressant-like effects thanks to its multicomponent character. Because depression is not caused by a single mechanism, probing the antidepressant-like effects of DXS could further help understand the pathogenesis of depression and discover new antidepressant drugs.

Effect of auricular acupuncture on neuroplasticity of stroke patients with motor dysfunction: A fNIRS study.

Cerebral Stroke is an acute cerebrovascular disease, a disease of brain tissue damage caused by the sudden rupture or blockage of blood vessels in the brain that prevents blood flow to the brain. Acupuncture has become a popular treatment for stroke, with auricular acupuncture providing a new idea for stroke treatment. However, the neuromodulatory mechanism of auricular acupuncture in the brain is still unclear. The aim of this study was to investigate the effect of auricular acupuncture in the treatment of upper limb dysfunction and the activation of specific brain regions in stroke patients. Forty patients with stroke hemiplegia who met the nerf criteria were included in the experiment and randomly assigned into two groups (20 patients in each group): the auricular acupuncture group and the control group. Fugl-Meyer score (FMA) assessment of upper limb motor function, motor evoked potential (MEP) measurement, and functional near-infrared brain function imaging (fNIRS) data acquisition in the primary motor M1 area of the brain at rest were performed before and after treatment, respectively. It was found that: 1) after auricular acupuncture treatment, the patients in the auricular acupuncture group showed significantly greater peak MEP and significantly higher oxyhemoglobin content in the M1 region of the brain compared with the control group, with a significant activation effect (MEP: P-value = 0.032, t = -2.22; HbO2; f = 4.225, p = 0.046); 2) in the clinical efficacy assessment, the FMA score in the auricular acupuncture group after treatment (p = 0.0122, t = 2.769). The results suggest that auricular acupuncture has an ameliorative effect on upper limb motor deficits after stroke and that activation of the M1 region of the brain may be a key node in auricular acupuncture for treating upper limb dysfunction in stroke patients, a finding that emphasizes the potential for clinical application of auricular acupuncture therapy for stroke patients with potential mechanisms influencing the outcome.

Virtual reality and motor imagery for early post-stroke rehabilitation.

BACKGROUND: Motor impairment is a common consequence of stroke causing difficulty in independent movement. The first month of post-stroke rehabilitation is the most effective period for recovery. Movement imagination, known as motor imagery, in combination with virtual reality may provide a way for stroke patients with severe motor disabilities to begin rehabilitation. METHODS: The aim of this study is to verify whether motor imagery and virtual reality help to activate stroke patients' motor cortex. 16 acute/subacute (< 6 months) stroke patients participated in this study. All participants performed motor imagery of basketball shooting which involved the following tasks: listening to audio instruction only, watching a basketball shooting animation in 3D with audio, and also performing motor imagery afterwards. Electroencephalogram (EEG) was recorded for analysis of motor-related features of the brain such as power spectral analysis in the [Formula: see text] and [Formula: see text] frequency bands and spectral entropy. 18 EEG channels over the motor cortex were used for all stroke patients. RESULTS: All results are normalised relative to all tasks for each participant. The power spectral densities peak near the [Formula: see text] band for all participants and also the [Formula: see text] band for some participants. Tasks with instructions during motor imagery generally show greater power spectral peaks. The p-values of the Wilcoxon signed-rank test for band power comparison from the 18 EEG channels between different pairs of tasks show a 0.01 significance of rejecting the band powers being the same for most tasks done by stroke subjects. The motor cortex of most stroke patients is more active when virtual reality is involved during motor imagery as indicated by their respective scalp maps of band power and spectral entropy. CONCLUSION: The resulting activation of stroke patient's motor cortices in this study reveals evidence that it is induced by imagination of movement and virtual reality supports motor imagery. The framework of the current study also provides an efficient way to investigate motor imagery and virtual reality during post-stroke rehabilitation.

Higher Dose Noninvasive Transcutaneous Auricular Vagus Nerve Stimulation Increases Feeding Volumes and White Matter Microstructural Complexity in Open-Label Study of Infants Slated for Gastrostomy Tube.

OBJECTIVE: To determine whether transcutaneous auricular vagus nerve stimulation (taVNS) paired with twice daily bottle feeding increases the volume of oral feeds and white matter neuroplasticity in term-age-equivalent infants failing oral feeds and determined to need a gastrostomy tube. STUDY DESIGN: In this prospective, open-label study, 21 infants received taVNS paired with 2 bottle feeds for 2 - 3 weeks (2x). We compared 1) increase oral feeding volumes with 2x taVNS and previously reported once daily taVNS (1x) to determine a dose response, 2) number of infants who attained full oral feeding volumes, and 3) diffusional kurtosis imaging and magnetic resonance spectroscopy before and after treatment by paired t tests. RESULTS: All 2x taVNS treated infants significantly increased their feeding volumes compared with 10 days before treatment. Over 50% of 2x taVNS infants achieved full oral feeds but in a shorter time than 1x cohort (median 7 days [2x], 12.5 days [1x], P < .05). Infants attaining full oral feeds showed greater increase in radial kurtosis in the right corticospinal tract at the cerebellar peduncle and external capsule. Notably, 75% of infants of diabetic mothers failed full oral feeds, and their glutathione concentrations in the basal ganglia, a measure of central nervous system oxidative stress, were significantly associated with feeding outcome. CONCLUSIONS: In infants with feeding difficulty, increasing the number of daily taVNS-paired feeding sessions to twice-daily significantly accelerates response time but not the overall response rate of treatment. taVNS was associated with white matter motor tract plasticity in infants able to attain full oral feeds. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04643808).

Exercise-induced hypothalamic neuroplasticity: Implications for energy and glucose metabolism.

BACKGROUND: Neuroplasticity refers to the brain's ability to undergo functional and structural changes in response to diverse challenges. Converging evidence supports the notion that exercise serves as a metabolic challenge, triggering the release of multiple factors both in the periphery and within the brain. These factors actively contribute to plasticity in the brain, and in turn, regulate energy and glucose metabolism. SCOPE OF REVIEW: The primary focus of this review is to explore the impact of exercise-induced plasticity in the brain on metabolic homeostasis, with an emphasis on the role of the hypothalamus in this process. Additionally, the review provides an overview of various factors induced by exercise that contribute to energy balance and glucose metabolism. Notably, these factors exert their effects, at least in part, through actions within the hypothalamus and more broadly in the central nervous system. MAJOR CONCLUSIONS: Exercise elicits both transient and sustained changes in metabolism, accompanied by changes in neural activity within specific brain regions. Importantly, the contribution of exercise-induced plasticity and the underlying mechanisms by which neuroplasticity influences the effects of exercise are not well understood. Recent work has begun to overcome this gap in knowledge by examining the complex interactions of exercise-induced factors which alter neural circuit properties to influence metabolism.

Circadian Factors in Stroke: A Clinician's Perspective.

Stroke remains one of the leading causes of mortality and long-term and permanent disability worldwide despite technological innovations and developments in pharmacotherapy. In the last few decades, the growing data have evidenced the role of the circadian system in brain vulnerability to damage, the development and evolution of stroke, and short-term and long-term recovery. On the other hand, the stroke itself can affect the circadian system via direct injury of specific brain structures involved in circadian regulation (i.e., hypothalamus, retinohypothalamic tracts, etc.) and impairment of endogenous regulatory mechanisms, metabolic derangement, and a neurogenic inflammatory response in acute stroke. Moreover, the disruption of circadian rhythms can occur or exacerbate as a result of exogenous factors related to hospitalization itself, the conditions in the intensive care unit and the ward (light, noise, etc.), medication (sedatives and hypnotics), and loss of external factors entraining the circadian rhythms. In the acute phase of stroke, patients demonstrate abnormal circadian variations in circadian biomarkers (melatonin, cortisol), core body temperature, and rest-activity patterns. The approaches aimed at the restoration of disrupted circadian patterns include pharmacological (melatonin supplementation) and non-medication (bright light therapy, shifting feeding schedules, etc.) interventions; however, their effects on short- and long-term recovery after stroke are not well understood.

[Effect of transcutaneous electrical acupoint stimulation on learning and memory ability of chronic fatigue syndrome rats and its mechanisms].

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on the histomorphological manifestations of hippocampal CA1 region and the expression of extracellular regulatory protein kinase (ERK), cyclic adenosine response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in chronic fatigue syndrome (CFS) rats, so as to explore the mechanisms of TEAS in improving the learning and memory abilities of CFS rats. METHODS: Forty male Wistar rats were randomly divided into normal group (10 rats) and modeling group (30 rats); then after modeling, they were selected and randomly divided into model group (10 rats) and TEAS group (10 rats). CFS rats model was prepared by sleep deprivation combined with weight-bearing swimming. Rats in the TEAS group were stimulated with Han's acupoint nerve stimulator at bilateral "Zusanli" (ST36) and "Shenshu" (BL23) (2 Hz/15 Hz, 1-2 mA), 20 min each time, once a day for 4 weeks with 1 d rest every 6 d. The score of general conditions of rats was evaluated. The learning and memory ability was tested with Morris water maze. The morphology and ultrastructure of hippocampal CA1 region were observed by HE staining and transmission electron microscopy. The expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were detected by real time quantitative PCR and Western blot, respectively. RESULTS: Compared with the normal group, the score of general condition was increased (P<0.01); the escape latency was prolonged (P<0.05, P<0.01) and the times of crossing the original platform was decreased (P<0.05); the expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were decreased (P<0.05, P<0.01) in the model group. Compared with the model group, the scores of general condition on the 42nd and 49th day were decreased (P<0.05, P<0.01); the escape latency was shortened (P<0.01, P<0.05)and the times of crossing the original platform were increased (P<0.05); the expression levels of ERK, CREB and BDNF mRNAs and proteins in hippocampus were increased (P<0.01, P<0.05) in the TEAS group. The morphology of neurons in hippocampal CA1 region was normal in the normal group. In the model group, the number of neurons in hippocampal CA1 region decreased, the arrangement of nerve cells was scattered, the number of apoptotic cells increased, some nuclear structures disappeared, nuclear heterochromatin increased, the cell membrane wrinkled, the chromatin appeared empty bright area, and the crista was incomplete. Compared with the model group, the nerve cells morphology in hippocampal CA1 region was more regular, the number of apoptotic cells decreased, the chromatin and the cytoplasm were uniformly distributed, and the crista was relatively intact in the TEAS group. CONCLUSION: TEAS can improve the learning and memory ability of CFS rats, the mechanisms may be related to improving the neural structure of hippocampal CA1 region and up-regulating the expression levels of ERK/CREB/BDNF.

14-3-3ζ Plays a key role in the modulation of neuroplasticity underlying the antidepressant-like effects of Zhi-Zi-Chi-Tang.

BACKGROUND: Zhi-Zi-Chi-Tang (ZZCT) is an effective traditional Chinese medicinal formula. ZZCT has been used for the treatment of depression for centuries. Its clinical efficacy in relieving depression has been confirmed. However, the molecular mechanisms of ZZCT regarding neuroplasticity in the pathogenesis of depression have not yet been elucidated. PURPOSE: The present study aimed to examine the effects of ZZCT on neuroplasticity in mice exposed to chronic unpredictable mild stress (CUMS), and to explore the underlying molecular mechanisms. METHODS: For this purpose, a murine model of depression was established using the CUMS procedure. Following the intragastric administration of ZZCT or fluoxetine, classic behavioral experiments were performed to observe the efficacy of ZZCT as an antidepressant. Immunofluorescence was used to label and quantify microtubule-associated protein (MAP2) and postsynaptic density protein (PSD95) in the hippocampus. Golgi staining was applied to visualize the dendritic spine density of neurons in the hippocampi. Isolated hippocampal slices were prepared to induce long-term potentiation (LTP) in the CA1 area. The hippocampal protein expression levels of glycogen synthase kinase-3ß (GSK-3ß), p-GSK-3ß (Ser9), cAMP response element binding protein (CREB), p-CREB (Ser133), brain-derived neurotrophic factor (BDNF) and 14-3-3ζ were detected using western blot analysis. The interaction of 14-3-3ζ and p-GSK-3ß (Ser9) was examined using co-immunoprecipitation. LV-shRNA was used to knockdown 14-3-3ζ by an intracerebroventricular injection. RESULTS: ZZCT (6 g/kg) and fluoxetine (20 mg/kg) alleviated depressive-like behavior, restored hippocampal MAP2+ PSD95+ intensity, and reversed the dendritic spine density of hippocampal neurons and LTP in the CA1 region of mice exposed to CUMS. Both low and high doses of ZZCT (3 and 6 g/kg) significantly promoted the binding of 14-3-3ζ to p-GSK-3ß (Ser9) in the hippocampus, and ZZCT (6 g/kg) significantly promoted the phosphorylation of GSK-3ß Ser9 and CREB Ser133 in the hippocampus. ZZCT (3 and 6 g/kg) upregulated hippocampal BDNF expression in mice exposed to CUMS. LV-sh14-3-3ξ reduced the antidepressant effects of ZZCT. CONCLUSION: ZZCT exerted antidepressant effects against CUMS-stimulated depressive-like behavior mice. The knockdown of 14-3-3ζ using lentivirus confirmed that 14-3-3ζ was involved in the ZZCT-mediated antidepressant effects through GSK-3ß/CREB/BDNF signaling. On the whole, these results suggest that the antidepressant effects of ZZCT are attributed to restoring damage by neuroplasticity enhancement via the 14-3-3ζ/GSK-3ß/CREB/BDNF signaling pathway.

Remote neurocognitive interventions for attention-deficit/hyperactivity disorder - Opportunities and challenges.

Improving neurocognitive functions through remote interventions has been a promising approach to developing new treatments for attention-deficit/hyperactivity disorder (AD/HD). Remote neurocognitive interventions may address the shortcomings of the current prevailing pharmacological therapies for AD/HD, e.g., side effects and access barriers. Here we review the current options for remote neurocognitive interventions to reduce AD/HD symptoms, including cognitive training, EEG neurofeedback training, transcranial electrical stimulation, and external cranial nerve stimulation. We begin with an overview of the neurocognitive deficits in AD/HD to identify the targets for developing interventions. The role of neuroplasticity in each intervention is then highlighted due to its essential role in facilitating neuropsychological adaptations. Following this, each intervention type is discussed in terms of the critical details of the intervention protocols, the role of neuroplasticity, and the available evidence. Finally, we offer suggestions for future directions in terms of optimizing the existing intervention protocols and developing novel protocols.

Effectiveness of mindfulness-based interventions on mental, cognitive outcomes and neuroplastic changes in older adults with mild cognitive impairment: A systematic review and meta-analysis.

AIMS: To evaluate the effectiveness of mindfulness-based interventions (MBIs) on mental and cognitive outcomes including, anxiety, depression, attention, memory, global cognition and neuroplastic changes in older adults with mild cognitive impairment (MCI). DESIGN: Systematic review and meta-analysis. DATA SOURCE: A three-step search strategy was conducted on eight electronic databases, grey literature and reference lists from inception to February 2022. REVIEW METHODS: Randomized controlled trials (RCTs) examining MBIs on older adults with MCI were screened and assessed for risk of bias using the Cochrane Risk of Bias Tool. Meta-analysis was conducted using RevMan using a random-effect model. Narrative synthesis was performed for studies where results could not be pooled statistically. RESULTS: Ten RCTs were included in the review. Results suggested that right frontal parietal and left inferior temporal gyrus of the brain showed increased cortical thickness after receiving MBIs. There were significant interaction effects for global efficiency and significant interactions in the insular and gyrus regions. Functional connectivity between the posterior cingulate cortex, bilateral medial prefrontal cortex and left hippocampus were increased in participants undergoing MBIs. Nevertheless, meta-analysis showed non-significant pooled effects, favouring control groups on anxiety, depression, attention, memory and global cognition. CONCLUSION: This review suggested the potential effects of MBIs in improving cortical thickness and connectivity in regions associated with memory and attention. Nevertheless, the effects of MBIs compared to active control groups on depression, anxiety, attention, memory and global cognition are inconclusive due to the lack of studies and non-significant results. IMPACT: The review advocates for more rigorous studies with larger sample size and utilizing wait-list controls to evaluate the effects of MBIs. MBIs can be considered as an adjunct with other therapies to further enhance the effect on psychological and cognitive outcomes for older adults with MCI. No Patient or Public Contribution as this is a meta-analysis.

Mechanisms of Action of Noninvasive Brain Stimulation with Weak Non-Constant Current Stimulation Approaches.

Objective: Non-constant current stimulation (NCCS) is a neuromodulatory method in which weak alternating, pulsed or random currents are delivered to the human head via scalp or earlobe electrodes. This approach is widely used in basic and translational studies. However, the underlying mechanisms of NCCS, which lead to biological and behavioral effects in the brain, remain largely unknown. In this review, we characterize NCCS techniques currently being utilized in neuroscience investigations, including transcranial alternating current stimulation (tACS), transcranial pulsed current stimulation (tPCS), transcranial random noise stimulation (tRNS), and cranial electrotherapy stimulation (CES). Method: We unsystematically searched all relevant conference papers, journal articles, chapters, and textbooks on the biological mechanisms of NCCS techniques. Results: The fundamental idea of NCCS is that these low-level currents can interact with neuronal activity, modulate neuroplasticity and entrain cortical networks, thus, modifying cognition and behavior. We elucidate the mechanisms of action for each NCCS technique. These techniques may cause microscopic effects (such as affecting ion channels and neurotransmission systems) and macroscopic effects (such as affecting brain oscillations and functional connectivity) on the brain through different mechanisms of action (such as neural entrainment and stochastic resonance). Conclusion: The appeal of NCCS is its potential to modulate neuroplasticity noninvasively, along with the ease of use and good tolerability. Promising and interesting evidence has been reported for the capacity of NCCS to affect neural circuits and the behaviors under their control. Today, the challenge is to utilize this advancement optimally. Continuing methodological advancements with NCCS approaches will enable researchers to better understand how NCCS can be utilized for the modulation of nervous system activity and subsequent behaviors, with possible applications to non-clinical and clinical practices.