Stimulation of dorsal root ganglion with low-intensity focused ultrasound ameliorates pain responses through the GABA inhibitory pathway.

Aims: Chronic pain is a critical public health issue that severely impacts quality of life and poses significant treatment challenges, particularly due to the risk of adverse effects associated with pharmacological therapies. The search for effective non-invasive treatment alternatives has become increasingly relevant. Low-intensity focused ultrasound (LIFU) has been identified as an effective non-invasive strategy for pain management, although the underlying mechanism remains unclear.

Supplementation with subsp. MH-022 for remission of motor impairments in a 6-OHDA-induced Parkinson's disease rat model by reducing inflammation, reshaping the gut microbiome, and fostering specific microbial taxa.

Inflammation significantly influences the degeneration of dopaminergic neurons in Parkinson's disease (PD), which is potentially intensified by associated gut dysbiosis. The therapeutic potential of probiotics, due to their antioxidant, anti-inflammatory, and gut microbiota modulatory properties, is explored herein as a means to improve gut health and influence the gut-brain-microbiota axis in the context of PD. In this study, we investigated the role and possible mechanism of subsp.

Hypothalamic NPFFR2 attenuates central insulin signaling and its knockout diminishes metabolic dysfunction in mouse models of diabetes mellitus.

Background: The hypothalamus is a crucial brain region that mediates the effects of insulin and leptin signals on peripheral metabolic functions. Previous research has shown that insulin signals in the hypothalamus act via multiple neuronal circuits and anabolic/catabolic pathways that converge on the vagus nerve and sympathetic fibers to coordinate energy metabolism in peripheral organs. Additionally, neuropeptide FF (NPFF) has been identified as a regulator of feeding behaviors and energy homeostasis in the hypothalamus, but the mechanisms underlying its involvement in metabolic control remain unclear.

Endonuclease VIII-like 1 deficiency potentiates nigrostriatal dopaminergic neuron degeneration in a male mouse model of Parkinson's disease.

Parkinson's disease (PD) is a common movement disorder caused by a characteristic loss of dopaminergic neurons in the substantia nigra and degeneration of dopamine terminals in the dorsal striatum. Previous studies have suggested that oxidative stress-induced DNA damage may be involved in PD pathogenesis, as steady-state levels of several types of oxidized nucleobases were shown to be elevated in PD brain tissues. These DNA lesions are normally removed from the genome by base excision repair, which is initiated by DNA glycosylase enzymes such as endonuclease VIII-like 1 (Neil1).

Targeting nanoparticle-conjugated microbubbles combined with ultrasound-mediated microbubble destruction for enhanced tumor therapy.

The stress of the abnormal stromal matrix of solid tumors is a major limiting factor that prevents drug penetration. Controlled, accurate, and efficient delivery of theranostic agents into tumor cells is crucial. Combining ultrasound with nanocarrierbased drug delivery systems have become a promising approach for targeted drug delivery in preclinical cancer therapy.

N-3 PUFA Ameliorates the Gut Microbiota, Bile Acid Profiles, and Neuropsychiatric Behaviours in a Rat Model of Geriatric Depression.

The brain-gut-microbiome (BGM) axis affects host bioinformation. N-3 polyunsaturated fatty acids (PUFAs) alleviate cognitive impairment and depression in older adults. This study investigated altered microbiota-bile acid signalling as a potential mechanism linking fish oil-induced gut changes in microbiota to alleviate psychological symptoms.

Knockout of NPFFR2 Prevents LPS-Induced Depressive-Like Responses in Mice.

The precise neural mechanisms underlying the pathogenesis of depression are largely unknown, though stress-induced brain inflammation and serotonergic plasticity are thought to be centrally involved. Moreover, we previously demonstrated that neuropeptide FF receptor 2 (NPFFR2) overexpression provokes depressive-like behaviors in mice. Here, we assess whether NPFFR2 is involved in priming of depressive-like behaviors and downregulation of serotonergic 1A receptor (5HT1AR) after lipopolysaccharide (LPS) treatment.

Correction to: The knockdown of Neuropeptide FF receptor 2 inhibits capsaicin-induced CGRP Upregulation in mouse trigeminal ganglion.

An amendment to this paper has been published and can be accessed via the original article.

Ablation of NPFFR2 in Mice Reduces Response to Single Prolonged Stress Model.

Mental stress is highly related to many clinical symptoms and disorders, as it activates the hypothalamic-pituitary-adrenocortical (HPA) axis to affect a wide variety of physiological functions. Furthermore, stress leads to the aberrations in HPA axis activity and disruptions of body homeostasis. It was previously shown that neuropeptide FF (NPFF) regulates the HPA axis through the activation of hypothalamus paraventricular nucleus (PVN), and genetic overexpression or pharmacological stimulation of NPFF receptor 2 (NPFFR2) triggers hyperactivity of HPA axis and suppresses behavioral correlates of emotion in mice.

Neuropeptide FF receptor 2 inhibits capsaicin-induced CGRP Upregulation in mouse trigeminal ganglion.

Background: Stimulation of trigeminovascular pathway is widely used to establish the headache animal model. Headache is a common neurological disorder, in which symptomatic attacks are mediated by calcitonin-gene-related peptide (CGRP). CGRP is synthesized and released from the trigeminal ganglion to transmit pain signals under stimulation.

Glibenclamide restores dopaminergic reward circuitry in obese mice through interscauplar brown adipose tissue.

Background: Obesity, a critical feature in metabolic disorders, is associated with medical depression. Recent evidence reveals that brown adipose tissue (BAT) activity may contribute to mood disorders, Adenosine triphosphate (ATP)-sensitive K (K) channels regulate BAT sympathetic nerve activity. However, the mechanism through which BAT activity affects mood control remains unknown.

Microbubble-facilitated ultrasound pulsation promotes direct α-synuclein gene delivery.

Intra-neuronal α-synuclein (αSNCA) aggregation are the leading cause of dopaminergic neuron degeneration in Parkinson's disease (PD). Most PD patients is linked with αSNCA gene mutations. Gene therapy shows therapeutic potential by packing gene into viral vectors to improve gene expression through stereotactic brain injections.

Neuropeptide FF modulates neuroendocrine and energy homeostasis through hypothalamic signaling.

Neuropeptide FF (NPFF) is known as a morphine-modulating peptide and was first isolated in 1985. It has been characterized as an RF-amide peptide. The traditional role of NPFF is mediation of the pain response, and it displays both anti-opioid and pro-opioid actions through central nervous system.

Dorsal Root Ganglia Isolation and Primary Culture to Study Neurotransmitter Release.

Dorsal root ganglia (DRG) contain cell bodies of sensory neurons. This type of neuron is pseudo-unipolar, with two axons that innervate peripheral tissues, such as skin, muscle and visceral organs, as well as the spinal dorsal horn of the central nervous system. Sensory neurons transmit somatic sensation, including touch, pain, thermal, and proprioceptive sensations.

Focused Ultrasound-Induced Blood-Brain Barrier Opening Enhances GSK-3 Inhibitor Delivery for Amyloid-Beta Plaque Reduction.

Alzheimer's disease (AD) is a neurodegenerative disease that is the leading cause of age-related dementia. Currently, therapeutic agent delivery to the CNS is a valued approach for AD therapy. Unfortunately, the CNS penetration is greatly hampered by the blood-brain barrier (BBB).

NPFFR2 Activates the HPA Axis and Induces Anxiogenic Effects in Rodents.

Neuropeptide FF (NPFF) belongs to the RFamide family and is known as a morphine-modulating peptide. NPFF regulates various hypothalamic functions through two receptors, NPFFR1 and NPFFR2. The hypothalamic-pituitary-adrenal (HPA) axis participates in physiological stress response by increasing circulating glucocorticoid levels and modulating emotional responses.

Neuropeptide FF increases M2 activation and self-renewal of adipose tissue macrophages.

The quantity and activation state of adipose tissue macrophages (ATMs) impact the development of obesity-induced metabolic diseases. Appetite-controlling hormones play key roles in obesity; however, our understanding of their effects on ATMs is limited. Here, we have shown that human and mouse ATMs express NPFFR2, a receptor for the appetite-reducing neuropeptide FF (NPFF), and that NPFFR2 expression is upregulated by IL-4, an M2-polarizing cytokine.

Activation of NPFFR2 leads to hyperalgesia through the spinal inflammatory mediator CGRP in mice.

Neuropeptide FF (NPFF) is recognized as an opioid modulating peptide that regulates morphine-induced analgesia. The aim of this study was to delineate the role of NPFFR2 in pain transmission. We found the expression levels of NPFF and NPFFR2 were increased in the lumbar dorsal horn of animals with CFA- and carrageenan-induced inflammation and both NPFFR2 over-expressing transgenic (NPFFR2-Tg) and NPFFR2 agonist-treated mice displayed hyperalgesia.

Chronic activation of NPFFR2 stimulates the stress-related depressive behaviors through HPA axis modulation.

Neuropeptide FF (NPFF) is a morphine-modulating peptide that regulates the analgesic effect of opioids, and also controls food consumption and cardiovascular function through its interaction with two cognate receptors, NPFFR1 and NPFFR2. In the present study, we explore a novel modulatory role for NPFF-NPFFR2 in stress-related depressive behaviors. In a mouse model of chronic mild stress (CMS)-induced depression, the expression of NPFF significantly increased in the hypothalamus, hippocampus, medial prefrontal cortex (mPFC) and amygdala.

Noninvasive and targeted gene delivery into the brain using microbubble-facilitated focused ultrasound.

Recombinant adeno-associated viral (rAAV) vectors are potentially powerful tools for gene therapy of CNS diseases, but their penetration into brain parenchyma is severely limited by the blood-brain barrier (BBB) and current delivery relies on invasive stereotactic injection. Here we evaluate the local, targeted delivery of rAAV vectors into the brains of mice by noninvasive, reversible, microbubble-facilitated focused ultrasound (FUS), resulting in BBB opening that can be monitored and controlled by magnetic resonance imaging (MRI). Using this method, we found that IV-administered AAV2-GFP (green fluorescence protein) with a low viral vector titer (1×10(9) vg/g) can successfully penetrate the BBB-opened brain regions to express GFP.

Associations between physical facilities and organizational participation and levels of physical activity of adults in Tainan, Taiwan.

Background: During the past decade many studies have endeavored to evaluate the relationships between environmental attributes and physical activity, but there is limited data on this subject in Taiwan. This is the first study to investigate both objective and subjective environments in relation to different levels of physical activity in adults in Tainan, Taiwan.

Methods: A 2-stage survey examining relationships between physical and social environments and physical activity was designed.

The serotype-independent but concentration-dependent enhancing antibodies among Thai dengue patients.

Antibody-dependent enhancement of infection (ADE) is central to explaining the development of severe disease at the end of post-dengue virus infection. Non-neutralizing anti-dengue antibodies bound to the dengue virion enhances the virus entrance into the target cells via the Fc receptor. The titer of enhancing antibodies in dengue patients is not determined during dengue virus infection.

Up-regulation of dorsal root ganglia BDNF and trkB receptor in inflammatory pain: an in vivo and in vitro study.

Background: During inflammation, immune cells accumulate in damaged areas and release pro-inflammatory cytokines and neurotrophins. Brain-derived neurotrophic factor (BDNF) plays a neuromodulatory role in spinal cord dorsal horn via the post-synaptic tyrosine protein kinase B (trkB) receptor to facilitate pain transmission. However, the precise role of BDNF and trkB receptor in the primary sensory neurons of dorsal root ganglia (DRG) during inflammation remains to be clarified.