Eugenol and its liposome-based nano carrier reduce anxiety by inhibiting glyoxylase-1 expression in mice

The most common form of psycho-social dysfunction is anxiety with depression being related closely without any age bar. They are present with combined state of sadness, confusion, stress, fear etc. Glyoxalase system contains enzyme named glyoxalase 1 (GLO1).It is a metabolic pathway which detoxifies alpha-oxo-aldehydes, particularly methylglyoxal (MG). Methylglyoxal is mainly made by the breakdown of the glycolytic intermediates, glyceraldehyde-3-phosphates and dihydroxyacetone phosphate. Glyoxylase-1 expression is also related with anxiety behavior. A casual role or GLO-1 in anxiety behavior by using viral vectors for over expression in the anterior cingulate cortex was found and it was found that local GLO-1 over expression increased anxiety behavior. The present study deals with the molecular mechanism of protective activity of eugenol against anxiolytic disorder. A pre-clinical animal study was performed on 42 BALB/c mice. Animals were given stress through conventional restrain model. The mRNA expression of GLO-1 was analyzed by real time RT-PCR. Moreover, the GLO-1 protein expression was also examined by immunohistochemistry in whole brain and mean density was calculated. The mRNA and protein expressions were found to be increased in animals given anxiety as compared to the normal control. Whereas, the expressions were decreased in the animals treated with eugenol and its liposome-based nanocarriers in a dose dependent manner. However, the results were better in animals treated with nanocarriers as compared to the compound alone. It is concluded that the eugenol and its liposome-based nanocarriers exert anxiolytic activity by down-regulating GLO-1 protein expression in mice.

A Functional Magnetic Resonance Imaging Study on Activation of Anterior Cingulate Cortex at Episode and Interictal Phases in Migraine

<sec> <title>Objective:</title> By using amplitude of low-frequency fluctuations (ALFF) we have analyzed activationsin brain regions at different phases in migraineurs. </sec> <sec> <title>Methods:</title> Participants included 41 patients with migraine, 19 in episode and 22 in interictal phase, and 22 controls in the healthy condition. To analyze the brain function of patients and controls, ALFF was used for performing the post-processing in the resting state by scores of Montreal Cognitive Assessment (MoCA) scale, Mini-Mental State Examination (MMSE), Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D). </sec> <sec> <title>Results:</title> The comparison between groups of patients with migraine in the episode or interictal phases, and healthy controls showed that both episode and interictal migraine groups had the similar HAM-A and HAM-D scores (P > 0.05), but higher than that in controls (P < 0.01). For ALFF values of Episode and Interictal groups, the Montreal Neurological Institute (MNI) coordinates of the decreased ALFF were (−9, 42, 9), the voxel size = 215, including the bilateral anterior cingulate cortex (ACC), T =−4.15, without significant differences. Patients in Interictal group were with a stronger activation at MNI coordinates (12, 51, 12), in the bilateral ACC, voxel size = 90, T =3.87. </sec> <sec> <title>Conclusion:</title> ACC plays an adaptive, regulatory role in migraine and is related to multiple brain regions, which may mediate activation through descending anti-nociceptive pathways. ACC is related to opioid receptor and glutamate excitatory regulation. </sec>

HIV-Associated Structural and Functional Brain Alterations in Homosexual Males

Purpose:Neuroimaging elucidations have shown structural and functional brain alterations in HIV-infected (HIV+) individuals when compared to HIV-negative (HIV–) controls. However, HIV− groups used in previous studies were not specifically considered for sexual orientation, which also affects the brain structures and functions. The current study aimed to characterize the brain alterations associated with HIV infection while controlling for sexual orientation.Methods:Forty-three HIV+ and 40 HIV– homosexual men (HoM) were recruited and underwent resting-state MRI scanning. Group differences in gray matter volume (GMV) were assessed using a voxel-based morphometry analysis. Brain regions with the altered GMV in the HIV+ HoM group were then taken as regions of interest in a seed-based analysis to identify altered functional connectivity. Furthermore, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity values were compared between the two groups to evaluate the HIV-associated functional abnormalities in local brain regions.Results:HIV+ HoM showed significantly increased GMV in the bilateral parahippocampal gyrus and amygdala, and decreased GMV in the right inferior cerebellum, compared with the HIV– HoM. The brain regions with increased GMV were hyper-connected with the left superior cerebellum, right lingual gyrus, and left precuneus in the HIV+ HoM. Moreover, the ALFF values of the right fusiform gyrus, and left parahippocampal gyrus were increased in the HIV+ HoM. The regional homogeneity values of the right anterior cingulate and paracingulate gyri, and left superior cerebellum were decreased in the HIV+ HoM.Conclusion:When the study population was restricted to HoM, HIV+ individuals exhibited structural alterations in the limbic system and cerebellum, and functional abnormalities in the limbic, cerebellum, and visual network. These findings complement the existing knowledge on the HIV-associated neurocognitive impairment from the previous neuroimaging studies by controlling for the potential confounding factor, sexual orientation. Future studies on brain alternations with the exclusion of related factors like sexual orientation are needed to understand the impact of HIV infection on neurocognitive function more accurately.

Investigation of Posture/Balance Disorder and Pd-related Pain by Using Diffusion Tensor Imaging and Transcranial Doppler

Background: Posture/balance disorder and pain are both present in Parkinson's patients, but their neural basis remain unclear. To investigate the central mechanism of posture/balance disorder and PD-related pain in Parkinson's disease by using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS), combined with Transcranial Doppler (TCD). Results: It was found that the dose of levodopa, UPDRSⅡ and UPDRSⅢ were higher value in the group with higher score of posture/balance. In the more severe posture/balance disorder group, the fiber bundles of the prefrontal cortex, anterior cingulate cortex and basal ganglia were more likely to be affected. In addition, the DTI parameter values of the three brain regions had a significant correlation with the parameter values of the corresponding arteries. In the analysis of PD-related pain, the white matter fiber bundles from the midbrain to the basal ganglia increased in patients with PD-related pain. There were no statistic difference in prevalence of PD-related pain was found between different groups according to posture/balance. Conclusions: Posture and balance in PD were correlated with the severity of the disease and the dosage of compound levodopa. Posture and balance in PD were related to changes in the white matter integrity of the prefrontal cortex, anterior cingulate cortex and basal ganglia. The function of cerebral arteries had contributions to white matter integrity of these area and posture/balance. PD-related pain was positively correlated with sleep score. Patients with PD-related pain had an increase in the fiber projection from the midbrain to the basal ganglia. No relation was found between posture/balance disorder with PD-related pain.

Functional Changes in Brain Activity Using Hypnosis: A Systematic Review

Hypnosis has proven a powerful method in indications such as pain control and anxiety reduction. As recently discussed, it has been yielding increased attention from medical/dental perspectives. This systematic review (PROSPERO-registration-ID-CRD42021259187) aimed to critically evaluate and discuss functional changes in brain activity using hypnosis by means of different imaging techniques. Randomized controlled trials, cohort, comparative, cross-sectional, evaluation and validation studies from three databases—Cochrane, Embase and Medline via PubMed from January 1979 to August 2021—were reviewed using an ad hoc prepared search string and following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. A total of 10404 articles were identified, 1194 duplicates were removed and 9190 papers were discarded after consulting article titles/abstracts. Ultimately, 20 papers were assessed for eligibility, and 20 papers were included after a hand search (ntotal = 40). Despite a broad heterogenicity of included studies, evidence of functional changes in brain activity using hypnosis was identified. Electromyography (EMG) startle amplitudes result in greater activity in the frontal brain area; amplitudes using Somatosensory Event-Related Potentials (SERPs) showed similar results. Electroencephalography (EEG) oscillations of θ activity are positively associated with response to hypnosis. EEG results showed greater amplitudes for highly hypnotizable subjects over the left hemisphere. Less activity during hypnosis was observed in the insula and anterior cingulate cortex (ACC).

Detailed measurements and simulations of electric field distribution of two TMS coils cleared for obsessive compulsive disorder in the brain and in specific regions associated with OCD

The FDA cleared deep transcranial magnetic stimulation (Deep TMS) with the H7 coil for obsessive-compulsive disorder (OCD) treatment, following a double-blinded placebo-controlled multicenter trial. Two years later the FDA cleared TMS with the D-B80 coil on the basis of substantial equivalence. In order to investigate the induced electric field characteristics of the two coils, these were placed at the treatment position for OCD over the prefrontal cortex of a head phantom, and the field distribution was measured. Additionally, numerical simulations were performed in eight Population Head Model repository models with two sets of conductivity values and three Virtual Population anatomical head models and their homogeneous versions. The H7 was found to induce significantly higher maximal electric fields (p<0.0001, t=11.08) and to stimulate two to five times larger volumes in the brain (p<0.0001, t=6.71). The rate of decay of electric field with distance is significantly slower for the H7 coil (p < 0.0001, Wilcoxon matched-pairs test). The field at the scalp is 306% of the field at a 3 cm depth with the D-B80, and 155% with the H7 coil. The H7 induces significantly higher intensities in broader volumes within the brain and in specific brain regions known to be implicated in OCD (dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus (IFG), orbitofrontal cortex (OFC) and pre-supplementary motor area (pre-SMA)) compared to the D-B80. Significant field ≥ 80 V/m is induced by the H7 (D-B80) in 15% (1%) of the dACC, 78% (29%) of the pre-SMA, 50% (20%) of the dlPFC, 30% (12%) of the OFC and 15% (1%) of the IFG. Considering the substantial differences between the two coils, the clinical efficacy in OCD should be tested and verified separately for each coil.

Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror-image pain following motor fiber injury

Background: Peripheral nerve inflammation or lesion can affect contralateral healthy structures, and thus results in mirror-image pain. Supraspinal structures play important roles in the occurrence of mirror pain. The anterior cingulate cortex (ACC) is a first order cortical region that responds to painful stimuli. In the present study, we systematically investigate and compare the neuroimmune changes in the bilateral ACC region using unilateral- (spared nerve injury, SNI) and mirror-(L5 ventral root transection, L5-VRT) pain models, aiming to explore the potential supraspinal neuroimmune mechanism underlying the mirror-image pain. Methods: The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Viral injections for the designer receptors exclusively activated by designer drugs (DREADD) were used to modulate ACC pyramidal neurons. Immunohistochemistry, immunofluorescence, western blotting, protein microarray were used to detect the regulation of inflammatory signaling.Results: Increased expressions of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and chemokine CX3CL1 in ACC induced by unilateral nerve injury were observed on the contralateral side in the SNI group but on the bilateral side in the L5-VRT group, representing a stronger immune response to L5-VRT surgery. In remote ACC, both SNI and L5-VRT induced robust bilateral increase in the protein level of Nav1.6 (SCN8A), a major voltage-gated sodium channel (VGSC) that regulates neuronal activity in the mammalian nervous system. However, the L5-VRT-induced Nav1.6 response occurred at PO 3d, earlier than the SNI-induced one, 7 days after surgery. Modulating ACC pyramidal neurons via DREADD-Gq or DREADD-Gi greatly changed the ACC CX3CL1 levels and the mechanical paw withdrawal threshold. Neutralization of endogenous ACC CX3CL1 by contralateral anti-CX3CL1 antibody attenuated the induction and the maintenance of mechanical allodynia and eliminated the upregulation of CX3CL1, TNF-α and Nav1.6 protein levels in ACC induced by SNI. Furthermore, contralateral ACC anti-CX3CL1 also inhibited the expression of ipsilateral spinal c-Fos, Iba1, CD11b, TNF-α and IL-6. Conclusions: The descending facilitation function mediated by CX3CL1 and its downstream cascade may play a pivotal role, leading to enhanced pain sensitization and even mirror-image pain. Strategies that target chemokine-mediated ACC hyperexcitability may lead to novel therapies for the treatment of neuropathic pain.

Acute effects of ketamine on the pregenual anterior cingulate: linking spontaneous activation, functional connectivity, and glutamate metabolism

Ketamine exerts its rapid antidepressant effects via modulation of the glutamatergic system. While numerous imaging studies have investigated the effects of ketamine on a functional macroscopic brain level, it remains unclear how altered glutamate metabolism and changes in brain function are linked. To shed light on this topic we here conducted a multimodal imaging study in healthy volunteers (N = 23) using resting state fMRI and proton (1H) magnetic resonance spectroscopy (MRS) to investigate linkage between metabolic and functional brain changes induced by ketamine. Subjects were investigated before and during an intravenous ketamine infusion. The MRS voxel was placed in the pregenual anterior cingulate cortex (pgACC), as this region has been repeatedly shown to be involved in ketamine’s effects. Our results showed functional connectivity changes from the pgACC to the right frontal pole and anterior mid cingulate cortex (aMCC). Absolute glutamate and glutamine concentrations in the pgACC did not differ significantly from baseline. However, we found that stronger pgACC activation during ketamine was linked to lower glutamine concentration in this region. Furthermore, reduced functional connectivity between pgACC and aMCC was related to increased pgACC activation and reduced glutamine. Our results thereby demonstrate how multimodal investigations in a single brain region could help to advance our understanding of the association between metabolic and functional changes.