STRUCTURE OF THE KNEE ARTICULAR CARTILAGE AFTER THE FEMUR AND TIBIA EXTRA-ARTICULAR INJURY.

OBJECTIVE: The aim: To study the microscopic, ultramicroscopic, and histomorphometric features of the knee articular cartilage in rats with an extra-articular injury of the femur and tibia. PATIENTS AND METHODS: Materials and methods: 60 white laboratory rats divided into three groups (I - control; II - animals with traumatic femur injury; III - animals with traumatic tibia injury) were used for the study. The light microscopy was performed by Olympus BH-2 microscope (Japan), transmission electron microscopy - by JEM-1230 microscope (Japan). SPSS software (version 17.0) was used for mathematical analysis. RESULTS: Results: The more pronounced morphological changes were observed in the articular cartilage of the proximal tibial epiphysis after mechanical tibial injury. The thickness of the articular cartilage was 27.89 % less than in the control. The chondrocyte number in the superficial zone was lower by 8.94 %, intermediate zone - by 14.23 %, and deep zone - by 21.83%, compared to control. Herewith, the histological changes were mostly detected in the intermediate and deep zones of the articular cartilage of both bones. Also, some chondrocytes had deformed nuclei, hypertrophied organelles, numerous inclusions, and residual glycogen granules. CONCLUSION: Conclusion: The extra-articular mechanical trauma of the lower limb bones leads to pathological changes in the knee articular cartilage. The structural changes include the articular cartilage thickening, the decrease in chondrocyte number, as well as chondrocyte rearrangement due to degenerative-dystrophic processes.

Neuronal Glutamate Transporters Control Dopaminergic Signaling and Compulsive Behaviors.

There is an ongoing debate on the contribution of the neuronal glutamate transporter EAAC1 to the onset of compulsive behaviors. Here, we used behavioral, electrophysiological, molecular, and viral approaches in male and female mice to identify the molecular and cellular mechanisms by which EAAC1 controls the execution of repeated motor behaviors. Our findings show that, in the striatum, a brain region implicated with movement execution, EAAC1 limits group I metabotropic glutamate receptor (mGluRI) activation, facilitates D1 dopamine receptor (D1R) expression, and ensures long-term synaptic plasticity. Blocking mGluRI in slices from mice lacking EAAC1 restores D1R expression and synaptic plasticity. Conversely, activation of intracellular signaling pathways coupled to mGluRI in D1R-containing striatal neurons of mice expressing EAAC1 leads to reduced D1R protein level and increased stereotyped movement execution. These findings identify new molecular mechanisms by which EAAC1 can shape glutamatergic and dopaminergic signals and control repeated movement execution.SIGNIFICANCE STATEMENT Genetic studies implicate Slc1a1, a gene encoding the neuronal glutamate transporter EAAC1, with obsessive-compulsive disorder (OCD). EAAC1 is abundantly expressed in the striatum, a brain region that is hyperactive in OCD. What remains unknown is how EAAC1 shapes synaptic function in the striatum. Our findings show that EAAC1 limits activation of metabotropic glutamate receptors (mGluRIs) in the striatum and, by doing so, promotes D1 dopamine receptor (D1R) expression. Targeted activation of signaling cascades coupled to mGluRIs in mice expressing EAAC1 reduces D1R expression and triggers repeated motor behaviors. These findings provide new information on the molecular basis of OCD and suggest new avenues for its treatment.