Oscillatory activity in the cortico‐basal ganglia‐thalamic neural circuits in Parkinson's disease

Abstract

Dopamine is an important neurotransmitter that maintains the balance within the basal ganglia between the direct pathway, which promotes movement, and the indirect pathway, which inhibits movement. Degeneration of dopaminergic neurons in the substantia nigra increases the influence of the indirect pathway, resulting in motor dysfunction in Parkinson's disease (PD). The direct and indirect pathways are composed of basal ganglia and thalamic nuclei, which are interconnected via independent parallel loop circuits with cortical areas and often referred to as cortico-basal ganglia-thalamic (CBT) neural circuits. CBT circuits have been useful in generating hypotheses to describe slowness in PD. Recent work has focused on aberrant neural oscillations within CBT circuits. Although beta (13-30 Hz) oscillations are a common feature of the CBT network, there is growing evidence that abnormally exaggerated beta oscillations, observed after dopamine loss in the CBT circuits, may contribute to motor symptoms of PD. Disruption of abnormal beta oscillations has been associated with the improvement of motor functions during pharmacological treatments, surgical lesions, and electrical stimulation. However, it is not clear how abnormal oscillations originate in the CBT motor network and resonate specifically in the beta band after the loss of dopamine. Most studies have addressed these questions by simultaneous recordings of oscillations in the motor cortex, basal ganglia nuclei, and motor regions of the thalamus in animal models of parkinsonism as well as in PD patients. This review further discusses previous and current studies of the changes in oscillatory activity at the level of CBT neural network in PD.

WWOX Tumor Suppressor Gene in Breast Cancer, a Historical Perspective and Future Directions

“…Surprisingly, contrary to animal studies, where WWOX inhibits tumorigenesis, elevated transcription of WWOX in MDA-MB-231 breast cancer cells was found to escalate migration through the basal membrane (Matrigel test), suggesting increased invasiveness (68). On the other hand, a morphogenesis test in Matrigel revealed MDA-MB-231 cells transduced with WWOX to display branched structures, compared with the spherical tumor-like structures of control cells.…”

“…Nevertheless, Wwox knockdown in a mouse model resulted in impaired mammary branching morphogenesis (72). Similar observations, were made on a breast cancer cell line, where ectopical overexpression of WWOX gene in MDA-MB-231 breast cancer cells changed cell growth in Matrigel from tumor-like to branched structures, which resembled normal mammary duct formation (68). …”

“…On the other hand, a morphogenesis test in Matrigel revealed MDA-MB-231 cells transduced with WWOX to display branched structures, compared with the spherical tumor-like structures of control cells. This results suggest that the WWOX gene might be involved in normal mammary tissue development (68). In ovarian cancer cell lines it was also observed that the restoration of WWOX modulated interaction of tumor cells with the extracellular matrix (67).…”

“…Soft agar growth assay showed the restoration of WWOX gene expression in breast cancer cell lines MDA-MB-453, T47D (31), BT-474, MDA-MB-231 (68, 69) and HCC1937 (69) significantly reduced their ability to anchor independent growth. Similar observations were reported for other WWOX -transduced cell lines from other cancers: pancreatic–AsPc1 and Panc1 (15, 16), prostate–DU145 (66), lung–A549, H460 and H1299 (65), and ovarian–A2780 (70).…”

Oscillatory Activity in the Cortex, Motor Thalamus and Nucleus Reticularis Thalami in Acute TTX and Chronic 6-OHDA Dopamine-Depleted Animals

“…Within the BG circuit, the sensory-motor thalamus (MTh) has critical role in motor information processing (58), but contrasting data exist concerning its neuronal activity in PD (59). According to the searchlight hypothesis , the nucleus reticularis thalami (NRT) has a fundamental role as the guardian of the thalamus, contributing to the encoding of thalamic information (60–68). In particular, the sensorimotor MTh is modulated by the NRT motor sector.…”