Age-Related Changes in the Temperature of the Lumbar Spine Measured by Passive Microwave Radiometry (MWR).

A study was conducted to determine the age dependence of the temperature of the low back in the region of the five lumbar vertebrae by using passive microwave radiometry (MWR). The rationale for the study is that the infrared brightness on which the temperature measurement is based will be dependent upon blood circulation and thus on metabolic, vascular, and other regulatory factors. The brightness and infrared temperatures were determined in five zones above each of the medial, left, and right lateral projections of the vertebrae.

Treatment and Companion Diagnostics of Lower Back Pain Using Self-Controlled Energo-Neuroadaptive Regulator (SCENAR) and Passive Microwave Radiometry (MWR).

Evaluation of the effectiveness of treatment of nonspecific lower back pain (LBP) is currently largely based on the patient's subjective feelings. The purpose of this study was to use passive microwave radiometry (MWR) as a tool for assessing the effectiveness of various treatment methods in patients with acute and subacute nonspecific LBP. Patients with a pain assessment on a visual analogue scale (VAS) of 6 to 10 points were divided into two groups: Group I included patients with pharmacological, syndrome-oriented treatment (n = 30, age 54.

Using medical microwave radiometry for brain temperature measurements.

Brain temperature (BT) is a crucial physiological parameter used to monitor cerebral status. Physical activities and traumatic brain injuries (TBI) can affect BT; therefore, non-invasive BT monitoring is an important way to gain insight into TBI, stroke, and wellbeing. The effects of BT on physical performance have been studied at length.

Microwave Radiometry (MWR) temperature measurement is related to symptom severity in patients with Low Back Pain (LBP).

Microwave Radiometry (MWR) has the advantage that measurements of internal (i.e. deep) tissue temperature may be obtained non-invasively by measuring naturally emitted radiation in GHz range.

Passive microwave radiometry in biomedical studies.

Passive microwave radiometry (MWR) measures natural emissions in the range 1-10GHz from proteins, cells, organs and the whole human body. The intensity of intrinsic emission is determined by biochemical and biophysical processes. The nature of this process is still not very well known.

Glutamate heteroreceptor complexes in the brain.

The existence of mGluR, NMDAR, AMPAR and putative KAR heteroreceptor complexes in synaptic and extrasynaptic regions of brain glutamate synapses represents a major integrative mechanism. Our aim in the current article is to analyze if the formation of the different types glutamate hetereceptor complexes involves the contribution of triplet amino acid homologies (protriplets) in a postulated receptor interface based on the triplet puzzle theory. Seven main sets (lists) of receptor pairs in databases were used containing various sets (lists) of human receptor heteromers and nonheteromers obtained from the available scientific publications including the publically available GPCR-hetnet database.

Existence of Brain 5-HT1A-5-HT2A Isoreceptor Complexes with Antagonistic Allosteric Receptor-Receptor Interactions Regulating 5-HT1A Receptor Recognition.

Studies on serotonin-selective reuptake inhibitors have established that disturbances in the ascending 5-HT neuron systems and their 5-HT receptor subtypes and collateral networks to the forebrain contribute to the etiology of major depression and are targets for treatment. The therapeutic action of serotonin-selective reuptake inhibitors is of proven effectiveness, but the mechanisms underlying their effect are still unclear. There are many 5-HT subtypes involved; some need to be blocked (e.

Understanding the Role of GPCR Heteroreceptor Complexes in Modulating the Brain Networks in Health and Disease.

The introduction of allosteric receptor-receptor interactions in G protein-coupled receptor (GPCR) heteroreceptor complexes of the central nervous system (CNS) gave a new dimension to brain integration and neuropsychopharmacology. The molecular basis of learning and memory was proposed to be based on the reorganization of the homo- and heteroreceptor complexes in the postjunctional membrane of synapses. Long-term memory may be created by the transformation of parts of the heteroreceptor complexes into unique transcription factors which can lead to the formation of specific adapter proteins.

IL1R2, CCR2, and CXCR4 May Form Heteroreceptor Complexes with NMDAR and D2R: Relevance for Schizophrenia.

The mild neuroinflammation hypothesis of schizophrenia was introduced by Bechter in 2001. It has been hypothesized that a hypofunction of glutamatergic signaling -methyl-D-aspartate receptors (NMDARs) and hyperactivation of dopamine D2 receptors play a role in schizophrenia. The triplet puzzle theory states that sets of triplet amino acid homologies guide two different receptors toward each other and contributes to the formation of a receptor heteromer.

Signaling in dopamine D2 receptor-oxytocin receptor heterocomplexes and its relevance for the anxiolytic effects of dopamine and oxytocin interactions in the amygdala of the rat.

Dopamine D2 receptor (D2R)-oxytocin receptor (OTR) interactions exist within heterocomplexes with facilitatory effects on D2R recognition and Gi/o coupling. In this work the hypothesis is tested using cotransfected HEK293 cells whether allosteric reciprocal D2R-OTR interactions can enhance signaling of D2R-OTR heterocomplexes along the CREB, MAPK and PLC pathways and whether the anxiolytic effects of OT may involve facilitatory D2R-OTR interactions within the central amygdaloid nucleus (CeA). Oxytocin enhanced the D2-like agonist quinpirole induced inhibition of the AC-PKA-pCREB signaling cascade and increased its signaling over the RAS-MAPK-pELK pathway.

FGFR1-5-HT1A Heteroreceptor Complexes: Implications for Understanding and Treating Major Depression.

The serotonin and neurotrophic factor hypotheses of depression are well known. The discovery of brain fibroblast growth factor receptor 1 (FGFR1)-5 hydroxytryptamine receptor 1A (5-HT1A) heteroreceptor complexes, and their enhancement of neuroplasticity, offers an integration of these hypotheses at the molecular level. They were first described in the hippocampus and later in midbrain 5-HT neurons, where these heterocomplexes are enriched in 5-HT1A autoreceptors.

The triplet puzzle theory indicates extensive formation of heteromers between opioid and chemokine receptor subtypes.

Biochemical studies had previously demonstrated examples of heteromerization between opioid and chemokine receptors. Based on the triplet puzzle theory, it has been discovered that opioid receptors are structurally more closely related to chemokine receptors than to other class A G-protein-coupled receptors. Their similarity is established in terms of the number of triplet homologies Asn-Leu-Ala, Thr-Leu-Pro, and Tyr-Ala-Phe in the amino acid code of extensive numbers of members of these two receptor groups.

The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural-glial networks.

Two major types of intercellular communication are found in the central nervous system (CNS), namely wiring transmission (point-to-point communication, the prototype being synaptic transmission with axons and terminals) and volume transmission (VT; communication in the extracellular fluid and in the cerebrospinal fluid (CSF)) involving large numbers of cells in the CNS. Volume and synaptic transmission become integrated inter alia through the ability of their chemical signals to activate different types of receptor protomers in heteroreceptor complexes located synaptically or extrasynaptically in the plasma membrane. The demonstration of extracellular dopamine (DA) and serotonin (5-HT) fluorescence around the DA and 5-HT nerve cell bodies with the Falck-Hillarp formaldehyde fluorescence method after treatment with amphetamine and chlorimipramine, respectively, gave the first indications of the existence of VT in the brain, at least at the soma level.

Enhancement of the FGFR1 signaling in the FGFR1-5-HT1A heteroreceptor complex in midbrain raphe 5-HT neuron systems. Relevance for neuroplasticity and depression.

New findings show existence of FGFR1-5-HT1A heteroreceptor complexes in 5-HT nerve cells of the dorsal and median raphe nuclei of the rat midbrain and hippocampus. Synergistic receptor-receptor interactions in these receptor complexes indicated their enhancing role in hippocampal plasticity. The existence of FGFR1-5-HT1A heteroreceptor complexes also in midbrain raphe 5-HT nerve cells open up the possibility that antidepressant drugs by increasing extracellular 5-HT levels can cause an activation of the FGF-2/FGFR1 mechanism in these nerve cells as well.

Evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes in the midbrain raphe 5-HT system.

The ascending midbrain 5-HT neurons known to contain 5-HT1A autoreceptors may be dysregulated in depression due to a reduced trophic support. With in situ proximity ligation assay (PLA) and supported by co-location of the FGFR1 and 5-HT1A immunoreactivities in midbrain raphe 5-HT cells, evidence for the existence of FGFR1-5-HT1A heteroreceptor complexes were obtained in the dorsal and median raphe nuclei of the Sprague-Dawley rat. Their existence in the rat medullary raphe RN33B cell cultures was also established.

Dopamine D2 heteroreceptor complexes and their receptor-receptor interactions in ventral striatum: novel targets for antipsychotic drugs.

This review is focused on the D2 heteroreceptor complexes within the ventral striatum with their receptor-receptor interactions and relevance for the treatment of schizophrenia. A "guide-and-clasp" manner for receptor-receptor interactions is proposed where "adhesive guides" may be amino acid triplet homologies, which were determined for different kinds of D2 heteroreceptor complexes. The first putative D2 heteroreceptor complex to be discovered in relation to schizophrenia was the A2A-D2 heteroreceptor complex where antagonistic A2A-D2 receptor-receptor interactions were demonstrated after A2A agonist treatment in the ventral striatum.

Diversity and Bias through Receptor-Receptor Interactions in GPCR Heteroreceptor Complexes. Focus on Examples from Dopamine D2 Receptor Heteromerization.

Allosteric receptor-receptor interactions in GPCR heteromers appeared to introduce an intermolecular allosteric mechanism contributing to the diversity and bias in the protomers. Examples of dopamine D2R heteromerization are given to show how such allosteric mechanisms significantly change the receptor protomer repertoire leading to diversity and biased recognition and signaling. In 1980s and 1990s, it was shown that neurotensin (NT) through selective antagonistic NTR-D2 like receptor interactions increased the diversity of DA signaling by reducing D2R-mediated dopamine signaling over D1R-mediated dopamine signaling.

Moonlighting proteins and protein-protein interactions as neurotherapeutic targets in the G protein-coupled receptor field.

There is serious interest in understanding the dynamics of the receptor-receptor and receptor-protein interactions in space and time and their integration in GPCR heteroreceptor complexes of the CNS. Moonlighting proteins are special multifunctional proteins because they perform multiple autonomous, often unrelated, functions without partitioning into different protein domains. Moonlighting through receptor oligomerization can be operationally defined as an allosteric receptor-receptor interaction, which leads to novel functions of at least one receptor protomer.

On the g-protein-coupled receptor heteromers and their allosteric receptor-receptor interactions in the central nervous system: focus on their role in pain modulation.

The modulatory role of allosteric receptor-receptor interactions in the pain pathways of the Central Nervous System and the peripheral nociceptors has become of increasing interest. As integrators of nociceptive and antinociceptive wiring and volume transmission signals, with a major role for the opioid receptor heteromers, they likely have an important role in the pain circuits and may be involved in acupuncture. The delta opioid receptor (DOR) exerts an antagonistic allosteric influence on the mu opioid receptor (MOR) function in a MOR-DOR heteromer.

Dopamine D2 receptor signaling dynamics of dopamine D2-neurotensin 1 receptor heteromers.

Biochemical, histochemical and coimmunoprecipitation experiments have indicated the existence of antagonistic dopamine D2 (D2R) and neurotensin 1 (NTS1R) receptor-receptor interactions in the dorsal and ventral striatum indicating a potential role of these receptor-receptor interactions in Parkinson's disease and schizophrenia. By means of Bioluminiscence Resonance energy transfer (BRET(2)) evidence has for the first time been obtained in the current study for the existence of both D2LR/NTS1R and D2SR/NTS1R heteromers in living HEK293T cells. Through confocal laser microscopy the NTS1R(GFP2) and D2R(YFP) were also shown to be colocated in the plasma membrane of these cells.

Integrin triplets of marine sponges in the murine and human MHCI-CD8 interface and in the interface of human neural receptor heteromers and subunits.

Based on our theory, main triplets of amino acid residues have been discovered in cell-adhesion receptors (integrins) of marine sponges, which participate as homologies in the interface between two major immune molecules, MHC class I (MHCI) and CD8αβ. They appear as homologies also in several human neural receptor heteromers and subunits. The obtained results probably mean that neural and immune receptors also utilize these structural integrin triplets to form heteromers and ion channels, which are required for a tuned and integrated intracellular and intercellular communication and a communication between cells and the extracellular matrix with an origin in sponges, the oldest multicellular animals.

G protein-coupled receptor heterodimerization in the brain.

G protein-coupled receptors (GPCRs) play critical roles in cellular processes and signaling and have been shown to form heteromers with diverge biochemical and/or pharmacological activities that are different from those of the corresponding monomers or homomers. However, despite extensive experimental results supporting the formation of GPCR heteromers in heterologous systems, the existence of such receptor heterocomplexes in the brain remains largely unknown, mostly because of the lack of appropriate methodology. Herein, we describe the in situ proximity ligation assay procedure underlining its high selectivity and sensitivity to image GPCR heteromers with confocal microscopy in brain sections.

On the existence and function of galanin receptor heteromers in the central nervous system.

Galanin receptor (GalR) subtypes 1-3 linked to central galanin neurons may form heteromers with each other and other types of G protein-coupled receptors in the central nervous system (CNS). These heteromers may be one molecular mechanism for galanin peptides and their N-terminal fragments (gal 1-15) to modulate the function of different types of glia-neuronal networks in the CNS, especially the emotional and the cardiovascular networks. GalR-5-HT1A heteromers likely exist with antagonistic GalR-5-HT1A receptor-receptor interactions in the ascending midbrain raphe 5-HT neuron systems and their target regions.

Integrin triplets of marine sponges in human D2 receptor heteromers.

The evidence for the existence of receptor heteromers opens up a new field for a better understanding of neural transmission. Based on our theory, we have discovered main triplets of amino acid residues in cell-adhesion receptors of marine sponges, which appear also as homologies in several dopamine D2 receptor heteromers of human brain. The obtained results probably mean a general molecular mechanism for receptor-receptor interactions in heteromers originated from the lowest animals (marine sponges).

Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks.

Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT) and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR) heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals.