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Cureus Jun 2023This article discusses the power of meditation and how beneficial it is for the body. Magnetic resonance imaging (MRI) has shown many positive brain changes and improved... (Review)
Review
This article discusses the power of meditation and how beneficial it is for the body. Magnetic resonance imaging (MRI) has shown many positive brain changes and improved several brain functions. Meditation has several benefits improving the immune system and inflammatory processes by decreasing cytokine; appropriate telomere shortening also has helped healthy aging. Regarding physical health, meditation has been beneficial in various multi-factorial diseases like diabetes, hypertension, and fibromyalgia. It has also helped bring down blood cholesterol levels and increase high-density lipoproteins (HDL) levels. Improvement was also seen in systolic and diastolic blood pressure. Mental health is another aspect influenced by meditation, as positive emotion brought about by meditation helps address various mental problems like social anxiety disorder, post-traumatic stress disorder (PTSD), anxiety, and depression. Overall, it seems to have some impact in all health areas. However, the magnitude of its effect is not known. More diverse and detailed studies should yield more beneficial clinical outcomes.
PubMed: 37476142
DOI: 10.7759/cureus.40650 -
Immunity Sep 2023Childhood neglect and/or abuse can induce mental health conditions with unknown mechanisms. Here, we identified stress hormones as strong inducers of astrocyte-mediated...
Childhood neglect and/or abuse can induce mental health conditions with unknown mechanisms. Here, we identified stress hormones as strong inducers of astrocyte-mediated synapse phagocytosis. Using in vitro, in vivo, and human brain organoid experiments, we showed that stress hormones increased the expression of the Mertk phagocytic receptor in astrocytes through glucocorticoid receptor (GR). In post-natal mice, exposure to early social deprivation (ESD) specifically activated the GR-MERTK pathway in astrocytes, but not in microglia. The excitatory post-synaptic density in cortical regions was reduced in ESD mice, and there was an increase in the astrocytic engulfment of these synapses. The loss of excitatory synapses, abnormal neuronal network activities, and behavioral abnormalities in ESD mice were largely prevented by ablating GR or MERTK in astrocytes. Our work reveals the critical roles of astrocytic GR-MERTK activation in evoking stress-induced abnormal behaviors in mice, suggesting GR-MERTK signaling as a therapeutic target for stress-induced mental health conditions.
Topics: Animals; Child; Humans; Mice; Astrocytes; c-Mer Tyrosine Kinase; Hormones; Phagocytosis; Synapses; Stress, Psychological
PubMed: 37527657
DOI: 10.1016/j.immuni.2023.07.005 -
Nature Communications Oct 2023Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein that is predominantly expressed by microglia in the brain. The proteolytic shedding...
Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein that is predominantly expressed by microglia in the brain. The proteolytic shedding of TREM2 results in the release of soluble TREM2 (sTREM2), which is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD). It remains unknown whether sTREM2 regulates the pathogenesis of AD. Here we identified transgelin-2 (TG2) expressed on neurons as the receptor for sTREM2. The microglia-derived sTREM2 binds to TG2, induces RhoA phosphorylation at S188, and deactivates the RhoA-ROCK-GSK3β pathway, ameliorating tau phosphorylation. The sTREM2 (77-89) fragment, which is the minimal active sequence of sTREM2 to activate TG2, mimics the inhibitory effect of sTREM2 on tau phosphorylation. Overexpression of sTREM2 or administration of the active peptide rescues tau pathology and behavioral defects in the tau P301S transgenic mice. Together, these findings demonstrate that the sTREM2-TG2 interaction mediates the cross-talk between microglia and neurons. sTREM2 and its active peptide may be a potential therapeutic intervention for tauopathies including AD.
Topics: Mice; Animals; Humans; Alzheimer Disease; Phosphorylation; Mice, Transgenic; Peptides; Cognition; tau Proteins; Biomarkers; Amyloid beta-Peptides; Membrane Glycoproteins; Receptors, Immunologic
PubMed: 37865646
DOI: 10.1038/s41467-023-42505-x -
Redox Biology Jun 2023Increasing studies have reported that intervertebral disc degeneration (IVDD) is the main contributor and independent risk factor for low back pain (LBP), it would be,...
Increasing studies have reported that intervertebral disc degeneration (IVDD) is the main contributor and independent risk factor for low back pain (LBP), it would be, therefore, enlightening that investigating the exact pathogenesis of IVDD and developing target-specific molecular drugs in the future. Ferroptosis is a new form of programmed cell death characterized by glutathione (GSH) depletion, and inactivation of the regulatory core of the antioxidant system (glutathione system) GPX4. The close relationship of oxidative stress and ferroptosis has been studied in various of diseases, but the crosstalk between of oxidative stress and ferroptosis has not been explored in IVDD. At the beginning of the current study, we proved that Sirt3 decreases and ferroptosis occurs after IVDD. Next, we found that knockout of Sirt3 (Sirt3) promoted IVDD and poor pain-related behavioral scores via increasing oxidative stress-induced ferroptosis. The (immunoprecipitation coupled with mass spectrometry) IP/MS and co-IP demonstrated that USP11 was identified to stabilize Sirt3 via directly binding to Sirt3 and deubiquitinating Sirt3. Overexpression of USP11 significantly ameliorate oxidative stress-induced ferroptosis, thus relieving IVDD by increasing Sirt3. Moreover, knockout of USP11 in vivo (USP11) resulted in exacerbated IVDD and poor pain-related behavioral scores, which could be reversed by overexpression of Sirt3 in intervertebral disc. In conclusion, the current study emphasized the importance of the interaction of USP11 and Sirt3 in the pathological process of IVDD via regulating oxidative stress-induced ferroptosis, and USP11-mediated oxidative stress-induced ferroptosis is identified as a promising target for treating IVDD.
Topics: Humans; Deubiquitinating Enzymes; Ferroptosis; Glutathione; Intervertebral Disc Degeneration; Nucleus Pulposus; Oxidative Stress; Pain; Sirtuin 3; Thiolester Hydrolases
PubMed: 37099926
DOI: 10.1016/j.redox.2023.102707 -
Neuron Aug 2023Autophagy disorders prominently affect the brain, entailing neurodevelopmental and neurodegenerative phenotypes in adolescence or aging, respectively. Synaptic and...
Autophagy disorders prominently affect the brain, entailing neurodevelopmental and neurodegenerative phenotypes in adolescence or aging, respectively. Synaptic and behavioral deficits are largely recapitulated in mouse models with ablation of autophagy genes in brain cells. Yet, the nature and temporal dynamics of brain autophagic substrates remain insufficiently characterized. Here, we immunopurified LC3-positive autophagic vesicles (LC3-pAVs) from the mouse brain and proteomically profiled their content. Moreover, we characterized the LC3-pAV content that accumulates after macroautophagy impairment, validating a brain autophagic degradome. We reveal selective pathways for aggrephagy, mitophagy, and ER-phagy via selective autophagy receptors, and the turnover of numerous synaptic substrates, under basal conditions. To gain insight into the temporal dynamics of autophagic protein turnover, we quantitatively compared adolescent, adult, and aged brains, revealing critical periods of enhanced mitophagy or degradation of synaptic substrates. Overall, this resource unbiasedly characterizes the contribution of autophagy to proteostasis in the maturing, adult, and aged brain.
Topics: Animals; Mice; Autophagy; Mitophagy; Macroautophagy; Aging; Brain
PubMed: 37279748
DOI: 10.1016/j.neuron.2023.05.011 -
Current Neurology and Neuroscience... Jul 2023Apraxia of speech (AOS) is a motor speech disorder that has long been recognized to occur secondary to acute neurologic insults and, more recently, to neurodegenerative... (Review)
Review
PURPOSE OF REVIEW
Apraxia of speech (AOS) is a motor speech disorder that has long been recognized to occur secondary to acute neurologic insults and, more recently, to neurodegenerative diseases as a harbinger for progressive supranuclear palsy and corticobasal syndrome. This article reviews recent findings regarding the clinic phenotypes of AOS, neuroimaging correlates, and the underlying disease processes.
RECENT FINDINGS
Two clinical subtypes of AOS map onto two underlying 4-repeat tauopathies. New imaging techniques have recently been applied to the study of progressive AOS. There is no data on the impact of behavioral intervention, although studies of nonfluent/agrammatic primary progressive aphasia that include patients with AOS suggest some benefit in speech intelligibility and maintenance. While recent findings suggest subtypes of AOS exist that are linked to molecular pathology and have important implications for disease progression, further research is needed to assess outcome of behavioral and other types of intervention.
Topics: Humans; Speech; Apraxias; Supranuclear Palsy, Progressive; Neuroimaging; Neurodegenerative Diseases
PubMed: 37269450
DOI: 10.1007/s11910-023-01275-1 -
Annals of Medicine and Surgery (2012) Oct 2023After only Alzheimer's disease (AD), Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. The incidence of this disease increases with age,... (Review)
Review
After only Alzheimer's disease (AD), Parkinson's disease (PD) is the second most prevalent neurodegenerative disease. The incidence of this disease increases with age, especially for those above 70 years old. There are many risk factors that are well-established in the contribution to the development of PD, such as age, gender, ethnicity, rapid eye movement sleep disorder, high consumption of dairy products, traumatic brain injury, genetics, and pesticides/herbicides. Interestingly, smoking, consumption of caffeine, and physical activities are the protective factors of PD. A deficiency of dopamine in the substantia nigra of the brainstem is the main pathology. This, subsequently, alters the neurotransmitter, causing an imbalance between excitatory and inhibitory signals. In addition, genetics is also involved in the pathogenesis of the disease. As a result, patients exhibit characteristic motor symptoms such as tremors, stiffness, bradykinesia, and postural instability, along with non-motor symptoms, including dementia, urinary incontinence, sleeping disturbances, and orthostatic hypotension. PD may resemble other diseases; therefore, it is important to pay attention to the diagnosis criteria. Parkinson's disease dementia can share common features with AD; this can include behavioral as well as psychiatric symptoms, in addition to the pathology being protein aggregate accumulation in the brain. For PD management, the administration of pharmacological treatment depends on the motor symptoms experienced by the patients. Non-pharmacological treatment plays a role as adjuvant therapy, while surgical management is indicated in chronic cases. This paper aims to review the etiology, risk factors, protective factors, pathophysiology, signs and symptoms, associated conditions, and management of PD.
PubMed: 37811009
DOI: 10.1097/MS9.0000000000001142