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Cytokine Sep 2011Cytokine-like factor 1 (CLF1) is a secreted receptor belonging to the interleukin-6 family of cytokines. CLF1 and its physiologic partner, cardiotrophin-like cytokine... (Review)
Review
Cytokine-like factor 1 (CLF1) is a secreted receptor belonging to the interleukin-6 family of cytokines. CLF1 and its physiologic partner, cardiotrophin-like cytokine (CLC) are secreted as a heterodimer and engage the tripartite signaling complex of ciliary neurotrophic factor receptor (CNTFR), leukemia inhibitory factor (LIFR) and gp130. Ligation of this receptor complex leads to activation of the STAT3 and MAPK pathways and mediates survival pathways in neurons. Mutations in CLF1, CLC, or CNTFR in mice lead to the birth of mice that die on post-natal day 1 because of an inability to nurse. These animals exhibit significant decreases in the number of motor neurons in the facial nucleus and the spinal cord. CLF1 or CLC deficiency is associated with the development of the human cold-induced sweating syndromes. A growing body of research suggests that CLF1 expression may be associated with several post-natal disease processes. In this review, we summarize the current understanding of CLF1 expression and suggest future studies to understand the potentially important role of CLF1 in postnatal life and disease.
Topics: Animals; Cytokine Receptor gp130; Cytokines; Humans; Interleukin-6; Leukemia Inhibitory Factor; MAP Kinase Signaling System; Mice; Mitogen-Activated Protein Kinases; Motor Neurons; Receptor, Ciliary Neurotrophic Factor; Receptors, Cytokine; Receptors, Interleukin-6; STAT3 Transcription Factor
PubMed: 21715184
DOI: 10.1016/j.cyto.2011.05.021 -
Autonomic Neuroscience : Basic &... Nov 2020Orexin (OX), which regulates sleep and wakefulness and feeding behaviors has 2 isoforms, orexin-A and -B (OXA and OXB). In this study, the distribution of OXA and OXB...
Orexin (OX), which regulates sleep and wakefulness and feeding behaviors has 2 isoforms, orexin-A and -B (OXA and OXB). In this study, the distribution of OXA and OXB was examined in the rat superior salivatory nucleus (SSN) using retrograde tracing and immunohistochemical and methods. OXA- and OXB-immunoreactive (-ir) nerve fibers were seen throughout the SSN. These nerve fibers surrounded SSN neurons retrogradely labeled with Fast blue (FB) from the corda-lingual nerve. FB-positive neurons had pericellular OXA- (47.5%) and OXB-ir (49.0%) nerve fibers. Immunohistochemistry for OX receptors also demonstrated the presence of OX1R and OX2R in FB-positive SSN neurons. The majority of FB-positive SSN neurons contained OX1R- (69.7%) or OX2R-immunoreactivity (57.8%). These neurons had small and medium-sized cell bodies. In addition, half of FB-positive SSN neurons which were immunoreactive for OX1R (47.0%) and OX2R (52.2%) had pericellular OXA- and OXB-ir nerve fibers, respectively. Co-expression of OX1R- and OX2R was common in FB-positive SSN neurons. The present study suggests a possibility that OXs regulate the activity of SSN neurons through OX receptors.
Topics: Animals; Autonomic Fibers, Preganglionic; Facial Nerve; Immunohistochemistry; Male; Orexin Receptors; Orexins; Rats; Rats, Wistar; Sublingual Gland; Submandibular Gland
PubMed: 32721850
DOI: 10.1016/j.autneu.2020.102712 -
Frontiers in Neuroscience 2023Clinical studies have revealed the existence of circadian rhythms in pain intensity and treatment response for chronic pain, including orofacial pain. The circadian...
INTRODUCTION
Clinical studies have revealed the existence of circadian rhythms in pain intensity and treatment response for chronic pain, including orofacial pain. The circadian clock genes in the peripheral ganglia are involved in pain information transmission by modulating the synthesis of pain mediators. However, the expression and distribution of clock genes and pain-related genes in different cell types within the trigeminal ganglion, the primary station of orofacial sensory transmission, are not yet fully understood.
METHODS
In this study, data from the normal trigeminal ganglion in the Gene Expression Omnibus (GEO) database were used to identify cell types and neuron subtypes within the human and mouse trigeminal ganglion by single nucleus RNA sequencing analysis. In the subsequent analyses, the distribution of the core clock genes, pain-related genes, and melatonin and opioid-related genes was assessed in various cell clusters and neuron subtypes within the human and mouse trigeminal ganglion. Furthermore, the statistical analysis was used to compare the differences in the expression of pain-related genes in the neuron subtypes of trigeminal ganglion.
RESULTS
The present study provides comprehensive transcriptional profiles of core clock genes, pain-related genes, melatonin-related genes, and opioid-related genes in different cell types and neuron subtypes within the mouse and human trigeminal ganglion. A comparative analysis of the distribution and expression of the aforementioned genes was conducted between human and mouse trigeminal ganglion to investigate species differences.
DISCUSSION
Overall, the results of this study serve as a primary and valuable resource for exploring the molecular mechanisms underlying oral facial pain and pain rhythms.
PubMed: 37250405
DOI: 10.3389/fnins.2023.1176654 -
Frontiers in Neuroscience 2018The treatment of psychiatric diseases with Deep Brain Stimulation (DBS) is becoming more of a reality as studies proliferate the indications and targets for therapies.... (Review)
Review
Closed Loop Deep Brain Stimulation for PTSD, Addiction, and Disorders of Affective Facial Interpretation: Review and Discussion of Potential Biomarkers and Stimulation Paradigms.
The treatment of psychiatric diseases with Deep Brain Stimulation (DBS) is becoming more of a reality as studies proliferate the indications and targets for therapies. Opinions on the initial failures of DBS trials for some psychiatric diseases point to a certain lack of finesse in using an Open Loop DBS (OLDBS) system in these dynamic, cyclical pathologies. OLDBS delivers monomorphic input into dysfunctional brain circuits with modulation of that input via human interface at discrete time points with no interim modulation or adaptation to the changing circuit dynamics. Closed Loop DBS (CLDBS) promises dynamic, intrinsic circuit modulation based on individual physiologic biomarkers of dysfunction. Discussed here are several psychiatric diseases which may be amenable to CLDBS paradigms as the neurophysiologic dysfunction is stochastic and not static. Post-Traumatic Stress Disorder (PTSD) has several peripheral and central physiologic and neurologic changes preceding stereotyped hyper-activation behavioral responses. Biomarkers for CLDBS potentially include skin conductance changes indicating changes in the sympathetic nervous system, changes in serum and central neurotransmitter concentrations, and limbic circuit activation. Chemical dependency and addiction have been demonstrated to be improved with both ablation and DBS of the Nucleus Accumbens and as a serendipitous side effect of movement disorder treatment. Potential peripheral biomarkers are similar to those proposed for PTSD with possible use of environmental and geolocation based cues, peripheral signs of physiologic arousal, and individual changes in central circuit patterns. Non-substance addiction disorders have also been serendipitously treated in patients with OLDBS for movement disorders. As more is learned about these behavioral addictions, DBS targets and effectors will be identified. Finally, discussed is the use of facial recognition software to modulate activation of inappropriate responses for psychiatric diseases in which misinterpretation of social cues feature prominently. These include Autism Spectrum Disorder, PTSD, and Schizophrenia-all of which have a common feature of dysfunctional interpretation of facial affective clues. Technological advances and improvements in circuit-based, individual-specific, real-time adaptable modulation, forecast functional neurosurgery treatments for heretofore treatment-resistant behavioral diseases.
PubMed: 29780303
DOI: 10.3389/fnins.2018.00300 -
Life (Basel, Switzerland) Aug 2022The pathophysiological mechanism underlying migraine-associated peripheral hypersensitivity remains unclear. Acid-sensing ion channels (ASICs) and transient receptor...
The pathophysiological mechanism underlying migraine-associated peripheral hypersensitivity remains unclear. Acid-sensing ion channels (ASICs) and transient receptor potential ankyrin 1 (TRPA1) are known to be causative pathogenic factors of mechanical and cold allodynia, respectively. Here, we sought to investigate their involvement in cold and mechanical allodynia of the face and hindpaws, respectively, in a mouse model of repetitive nitroglycerin (NTG)-induced migraine. NTG (10 mg/kg) was administered to the mice every other day for 9 days, followed 90 min later by HC-030031 (a TRPA1 blocker) or amiloride (a non-selective ASIC blocker). Mechanical or cold sensitivity of the hindpaw and facial regions was quantified using von-Frey filaments or acetone solution, respectively. Immunohistochemistry revealed that c-Fos expression was significantly increased in the trigeminal nucleus caudalis region but not in the spinal cord. Amiloride treatment only reduced NTG-induced hindpaw mechanical allodynia, whereas HC-030031 treatment only improved facial cold allodynia. Interestingly, the number of c-Fos positive cells decreased to a similar level in each drug treatment group. These findings demonstrate that facial cold allodynia and hindpaw mechanical allodynia are differentially mediated by activation of TRPA1 and ASIC, respectively, in mice with repetitive NTG-induced hypersensitivity.
PubMed: 36143331
DOI: 10.3390/life12091294 -
PloS One 2020Neurotrophic factor prosaposin (PS) is a precursor for saposins A, B, C, and D, which are activators for specific sphingolipid hydrolases in lysosomes. Both saposins and...
Neurotrophic factor prosaposin (PS) is a precursor for saposins A, B, C, and D, which are activators for specific sphingolipid hydrolases in lysosomes. Both saposins and PS are widely contained in various tissues. The brain, skeletal muscle, and heart cells predominantly contain unprocessed PS rather than saposins. PS and PS-derived peptides stimulate neuritogenesis and increase choline acetyltransferase activity in neuroblastoma cells and prevent programmed cell death in neurons. We previously detected increases in PS immunoactivity and its mRNA in the rat facial nucleus following facial nerve transection. PS mRNA expression increased not only in facial motoneurons, but also in microglia during facial nerve regeneration. In the present study, we examined the changes in immunoreactivity of the PS receptors GPR37 and GPR37L1 in the rat facial nucleus following facial nerve transection. Following facial nerve transection, many small Iba1- and glial fibrillary acidic protein (GFAP)-positive cells with strong GPR37L1 immunoreactivity, including microglia and astrocytes, were observed predominately on the operated side. These results indicate that GPR37 mainly works in neurons, whereas GPR37L1 is predominant in microglia or astrocytes, and suggest that increased PS in damaged neurons stimulates microglia or astrocytes via PS receptor GPR37L1 to produce neurotrophic factors for neuronal recovery.
Topics: Animals; Astrocytes; Facial Nerve; Facial Nucleus; Gene Expression Regulation; Humans; Microglia; Motor Neurons; Nerve Regeneration; Nerve Tissue Proteins; RNA, Messenger; Rats; Receptors, G-Protein-Coupled; Saposins
PubMed: 33259479
DOI: 10.1371/journal.pone.0241315 -
Cells Oct 2022Facial motoneuron (FMN) survival is mediated by CD4+ T cells in an interleukin-10 (IL-10)-dependent manner after facial nerve axotomy (FNA), but CD4+ T cells themselves...
Facial motoneuron (FMN) survival is mediated by CD4+ T cells in an interleukin-10 (IL-10)-dependent manner after facial nerve axotomy (FNA), but CD4+ T cells themselves are not the source of this neuroprotective IL-10. The aims of this study were to (1) identify the temporal and cell-specific induction of IL-10 expression in the facial motor nucleus and (2) elucidate the neuroprotective capacity of this expression after axotomy. Immunohistochemistry revealed that FMN constitutively produced IL-10, whereas astrocytes were induced to make IL-10 after FNA. mRNA co-localized with microglia before and after axotomy, but microglial production of IL-10 protein was not detected. To determine whether any single source of IL-10 was critical for FMN survival, Cre/Lox mouse strains were utilized to selectively knock out IL-10 in neurons, astrocytes, and microglia. In agreement with the localization data reflecting concerted IL-10 production by multiple cell types, no single cellular source of IL-10 alone could provide neuroprotection after FNA. These findings suggest that coordinated neuronal and astrocytic IL-10 production is necessary for FMN survival and has roles in neuronal homeostasis, as well as neuroprotective trophism after axotomy.
Topics: Animals; Mice; Axotomy; Facial Nerve Injuries; Facial Nucleus; Interleukin-10; Mice, Inbred C57BL; Mice, Knockout; Motor Neurons; Neuroprotection; RNA, Messenger
PubMed: 36231129
DOI: 10.3390/cells11193167 -
Journal of Chemical Neuroanatomy Dec 2022Axotomy of the rat facial nerve causes downregulation of motoneuron-specific molecules, including choline acetyltransferase and the vesicular acetylcholine transporter,...
Axotomy of the rat facial nerve causes downregulation of motoneuron-specific molecules, including choline acetyltransferase and the vesicular acetylcholine transporter, in surviving motoneurons. Subsequently, resident microglia are activated and proliferate. These cellular responses are thought to promote the survival, repair and regeneration of motoneurons. However, it is still unclear which signaling molecules are involved in these responses. In this study, we investigated the changes and localizations of several signaling molecules, including immediate early genes (IEGs) such as c-Jun and c-Fos, transcription factors such as cAMP responsive element binding protein (CREB) and activating transcription factor 2 (ATF2), and mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38. Immunoblotting and immunohistochemical analyses revealed the following. Among the IEGs, c-Jun was increased in injured motoneurons, but c-Fos did not respond to neuronal injury. Among the CREB/ATF family members, phosphorylated CREB (p-CREB) was significantly decreased in injured motoneurons. The levels of p-CREB/CREB and ATF2 were immunohistochemically increased in microglia. Among MAPKs, p-ERK1/2 and p-JNK1 were decreased in injured motoneurons at the late stage. p-p38 and p38 were markedly increased in microglia. In vitro experiments revealed that p38 and CREB were activated in proliferating microglia. These results strongly suggested that c-Jun is involved in the survival, repair and regeneration of motoneurons, but p-CREB/CREB, p-ERK/ERK and p-JNK/JNK are associated with the downregulation of motoneuron-specific molecules. On the other hand, p-p38/p38 and p-CREB/CREB were suggested to be closely involved in the activation/proliferation of microglia.
Topics: Animals; Rats; p38 Mitogen-Activated Protein Kinases; Facial Nucleus; Mitogen-Activated Protein Kinases; Cyclic AMP Response Element-Binding Protein; Signal Transduction; Proto-Oncogene Proteins c-fos; Phosphorylation
PubMed: 36341893
DOI: 10.1016/j.jchemneu.2022.102179 -
BMC Neurology May 2021The course of the corticobulbar tract (CBT) to the facial nucleus has been investigated by some previous studies. However, there are some unclear points of the course of...
BACKGROUND
The course of the corticobulbar tract (CBT) to the facial nucleus has been investigated by some previous studies. However, there are some unclear points of the course of the CBT to the facial nucleus. This study aimed to elucidate the detailed course of the CBT to the facial nucleus through the analysis of lateral medullary infarction (LMI) cases.
METHODS
The neurological characteristics and magnetic resonance imaging findings of 33 consecutive patients with LMI were evaluated. The location of the lesions was classified rostro-caudally (upper, middle, or lower) and horizontally. Further, we compared the neurological characteristics between the groups with and without central facial paresis (FP).
RESULTS
Eight (24%) patients with central FP ipsilateral to the lesion were identified. Dysphagia and hiccups were more frequently observed in the group with central FP than in the group without central FP. In patients with central FP, middle medullary lesions and those including the ventral part of the dorsolateral medulla were more frequently observed. Contrastingly, patients with lesions restricted to the lateral and dorsal regions of the dorsolateral medulla did not present with central FP.
CONCLUSION
The results of this study indicate that the CBT to the facial nucleus descends with the corticospinal tract at least to the middle portion of the medulla, and then ascends to the facial nucleus through the medial and ventral areas of the dorsolateral medulla after decussation.
Topics: Facial Paralysis; Humans; Magnetic Resonance Imaging; Medulla Oblongata; Pyramidal Tracts
PubMed: 34058995
DOI: 10.1186/s12883-021-02247-z -
The Anatomical Record. Part A,... Nov 2005The facial motor nucleus (VII) contains motoneurons that innervate the facial muscles of expression. In this review, the comparative anatomy of this brainstem nucleus is... (Comparative Study)
Comparative Study Review
The facial motor nucleus (VII) contains motoneurons that innervate the facial muscles of expression. In this review, the comparative anatomy of this brainstem nucleus is examined. Several aspects of the anatomical organization of the VII appear to be common across mammals, such as the distribution of neuron types, general topography of muscle representation, and afferent connections from the midbrain and brainstem. Phylogenetic specializations are apparent in the proportion of neurons allocated to the representation of subsets of muscles and the degree of differentiation among subnuclei. These interspecific differences may be related to the elaboration of certain facial muscles in the context of socioecological adaptations such as whisking behavior, sound localization, vocalization, and facial expression. Furthermore, current evidence indicates that direct descending corticomotoneuron projections in the VII are present only in catarrhine primates, suggesting that this connectivity is an important substrate for the evolution of enhanced mobility and flexibility in facial expression. Data are also presented from a stereologic analysis of VII neuron numbers in 18 primate species and a scandentian. Using phylogenetic comparative statistics, it is shown that there is not a correlation between group size and VII neuron number (adjusted for medulla volume) among primates. Great apes and humans, however, display moderately more VII neurons that expected for their medulla size.
Topics: Anatomy, Comparative; Animals; Biological Evolution; Facial Muscles; Facial Nerve; Humans; Motor Neurons; Primates
PubMed: 16200649
DOI: 10.1002/ar.a.20259