Research Spotlight

Zhang, Z., Y. Jing, Y. Ma, D. Duan, B. Li, C. Hölscher, C. Li, J. Wei, A. Gao, L. Shang, F. Tao and Y. Xing (2020). “Driving GABAergic neurons optogenetically improves learning, reduces amyloid load and enhances autophagy in a mouse model of Alzheimer’s disease.” Biochem Biophys Res Commun 525(4): 928-935.

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The changes of local field potentials (LFP, mainly gamma rhythm and theta rhythm) in the brain are closely related to learning and memory formation. Reduced gamma rhythm (20-50 Hz) and theta rhythm (4-10 Hz) has been observed in the progression of Alzheimer’s disease (AD), but it is not clear whether it is related to cognition in AD. Here, we investigated behaviorally driven gamma rhythm and theta rhythm in APP/PS1 mice, and optogenetically stimulated GABAergic neurons in the brain to better understand the relationship between the changes of LFP, cognition, and cellular pathologies. Optogenetically driving GABAergic neurons rescued memory formation in a water maze task and normalized theta and gamma rhythm in the EEG. Furthermore, the optogenetic stimulation alleviated neuroinflammation and levels of amyloid-β (Aβ)1-42 fragments, and induced autophagy. GABA blockers also reversed the normalization of theta and gamma rhythms in the brain by optogenetic stimulation. The results demonstrate that stimulation of GABAergic interneurons not only rescues LFP rhythms and memory formation, but furthermore activates autophagy and reduces neuroinflammation, which have beneficial additional effects such as clearing amyloid. This is a proof of concept for a novel therapeutic approach to AD treatment.

Taylor, R. W., G. K. Mitchell, J. L. Andrade and K. K. Svoboda (2020). “Expression of Collagen Types I, II, IX, and X in the Mineralizing Turkey Gastrocnemius Tendon.” Anat Rec (Hoboken) 303(6): 1664-1669.

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The turkey gastrocnemius tendon mineralizes by intramembranous ossification with a transient chondrogenic phase. The mineralizing zone has hypertrophic chondrocytes similar to endochondral bone formation. These similarities prompted the evaluation of this tendon for the presence of type X collagen in the mineralizing zone. Tendons were removed, radiographed, decalcified, and embedded for frozen sections. Seral sections were H&E stained and immunostained individually with antibodies specific collagens (types I, II, IX, and X). Type I collagen was distributed widely throughout the mineralized tendon extracellular matrix. Types II and IX collagen were at the mineralized/non-mineralized junction. Type X collagen was in the pericellular matrix of hypertrophic chondrocytes and in some calcified matrix. These data support the theory that the gastrocnemius tendon has fibrocartilage characteristics and that type X collagen has a role in the tissue’s mineralization.

Svoboda, K. K. H. and M. K. Gordon (2020). “Extracellular matrix: The proteins that function throughout the body.” Anat Rec (Hoboken) 303(6): 1509-1513.

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The idea and meetings that planned this issue focused on extracellular matrix (ECM) started over 4 years ago. The invitations were sent to investigators over 2 years ago and manuscripts have been submitted, reviewed, and edited since the summer and fall of 2018. Most of the manuscripts were published in early view in 2019, and we are thrilled to share the final collection. This volume contains 6 reviews, 13 original research papers, and 4 remembrances. Marion (Emmy) Gordon and I organized the articles into seven topic areas, including ECM structure, genetics, and development; cancer; vascular structures and development; inflammation and wound healing; collagen in special structures; cornea and other ocular tissues; and extracellular vesicles.

Shu, H., S. Liu, Y. Tang, B. L. Schmidt, J. C. Dolan, L. L. Bellinger, P. R. Kramer, S. D. Bender and F. Tao (2020). “A Pre-Existing Myogenic Temporomandibular Disorder Increases Trigeminal Calcitonin Gene-Related Peptide and Enhances Nitroglycerin-Induced Hypersensitivity in Mice.” Int J Mol Sci 21(11).

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Migraine is commonly reported among patients with temporomandibular disorders (TMDs), especially myogenic TMD. The pathophysiologic mechanisms related to the comorbidity of the two conditions remain elusive. In the present study, we combined masseter muscle tendon ligation (MMTL)-produced myogenic TMD with systemic injection of nitroglycerin (NTG)-induced migraine-like hypersensitivity in mice. Facial mechanical allodynia, functional allodynia, and light-aversive behavior were evaluated. Sumatriptan, an FDA-approved medication for migraine, was used to validate migraine-like hypersensitivity. Additionally, we examined the protein level of calcitonin gene-related peptide (CGRP) in the spinal trigeminal nucleus caudalis using immunohistochemistry. We observed that mice with MMTL pretreatment have a prolonged NTG-induced migraine-like hypersensitivity, and MMTL also enabled a non-sensitizing dose of NTG to trigger migraine-like hypersensitivity. Systemic injection of sumatriptan inhibited the MMTL-enhanced migraine-like hypersensitivity. MMTL pretreatment significantly upregulated the protein level of CGRP in the spinal trigeminal nucleus caudalis after NTG injection. Our results indicate that a pre-existing myogenic TMD can upregulate NTG-induced trigeminal CGRP and enhance migraine-like hypersensitivity.

Revilla-León, M., S. G. Subramanian, M. Özcan and V. R. Krishnamurthy (2020). “Clinical Study of the Influence of Ambient Lighting Conditions on the Mesh Quality of an Intraoral Scanner.” J Prosthodont May 28. [Epub ahead of print.].

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PURPOSE: To compute the effect of ambient light illuminance settings on the mesh quality of the digital scans accomplished in a subject. MATERIAL AND METHODS: A subject was recruited. The maxillary dentition did not present any dental restoration. A prosthodontist recorded different complete-arch maxillary digital scans by using an IOS (TRIOS 3; 3Shape) under 4 different illuminance light conditions namely chair light at 10 000-lux illuminance (CL group), room light at 1000-lux illuminance (RL group), natural light at 500-lux illuminance (NL group), and no light at 0-lux luminosity (ZL group). Ten digital scans for each group were consecutively obtained. Mesh quality was examined using the iso2mesh MATLAB package. Shapiro-Wilk test revealed a non-normally distributed data. Kruskal-Wallis one-way ANOVA, and pair-wise comparison were selected to evaluate the data (α = .05). RESULTS: Significant differences in mesh quality values were measured among the groups (P<.001). Pair-wise comparisons revealed that significant difference was found across all pairs of lighting groups, except for the RL-NL comparison (P = .279). However, the CL condition obtained the highest mean values, followed by RL and NL groups, and the lowest mean values were obtained on the ZL lighting condition. CONCLUSIONS: Chair light at 10 000-lux illuminance condition is recommended to maximize the quality mesh values of the IOS system tested (TRIOS 3; 3Shape).