Neuroscience
-
The role of the dopamine D2 receptor (D2R) in regulating appetitive behavior continues to be controversial. Earlier literature suggests that reduced D2R signaling diminishes motivated behavior while more recent theories suggest that reduced D2R, as has been putatively observed in obesity, facilitates compulsive appetitive behavior and promotes overeating. Using a homecage foraging paradigm with mice, we revisit classic neuroleptic pharmacological studies from the 1970s that led to the 'extinction mimicry' hypothesis: that dopamine blockade reduces reinforcement leading to an extinction-like reduction in a learned, motivated behavior. ⋯ The selective knockouts exhibit no change in sucrose preference or sucrose reinforcement. These data suggest that striatal D2R regulates effort in response to costs, mediating cost sensitivity and behavioral thrift. In the context of obesity, these data suggest that reduced D2R is more likely to diminish effort and behavioral energy expenditure rather than increase appetitive motivation and consumption, possibly contributing to reduced physical activity commonly observed in obesity.
-
Static magnetic field (SMF) is gaining interest as a potential technique for modulating CNS neuronal activity. Previous studies have shown a pro-neurogenic effect of short periods of extremely low frequency pulsatile magnetic fields (PMF) in vivo and pro-survival effect of low intensity SMF in cultured neurons in vitro, but little is known about the in vivo effects of low to moderate intensity SMF on brain functions. We investigated the effect of continuously-applied SMF on subventricular zone (SVZ) neurogenesis and immature doublecortin (DCX)-expressing cells in the neocortex of young adult rats and in primary cultures of cortical neurons in vitro. ⋯ We found that low intensity SMF exposure enhances cell proliferation in SVZ and new DCX-expressing cells in neocortical regions of young adult rats. In primary cortical neuronal cultures, SMF exposure increased the expression of newly generated cells co-labelled with EdU and DCX or the mature neuronal marker NeuN, while activating a set of pro neuronal bHLH genes. SMF exposure has potential for treatment of neurodegenerative disease and conditions such as CNS trauma and affective disorders in which increased neurogenesis is desirable.
-
Thioredoxin family proteins are key modulators of cellular redox regulation and have been linked to several physiological functions, including the cellular response to hypoxia-ischemia. During perinatal hypoxia-ischemia (PHI), the central nervous system is subjected to a fast decrease in O2 and nutrients with a subsequent reoxygenation that ultimately leads to the production of reactive species impairing physiological redox signaling. Particularly, the retina is one of the most affected tissues, due to its high oxygen consumption and exposure to light. ⋯ Knock-down of Trx1 in ARPE-19 cells affected cell morphology, proliferation and the levels of specific differentiation markers. Administration of recombinant Trx1 decreased astrogliosis and improved delayed neurodevelopment in animals exposed to PHI. Taken together, our results suggest therapeutical implications for Trx1 in retinal damage induced by hypoxia-ischemia during birth.
-
It has long been known that each neuron in both the central and peripheral nervous system has a large number of active zones. Nonetheless, how active zones are regulated to maintain a homeostatic release state and response to the constantly changing environment remains poorly understood. Due to its relatively simple structure and easy accessibility, the neuromuscular synapse (NM-synapse) continues to be used as a model synapse to examine the basic nature of synaptic neurotransmission. ⋯ Furthermore, evoked quantal release has been shown to be highly non-uniform between active zones along nerve terminal branches. How these large numbers of active zones along the same nerve terminal are functionally correlated remains unclear. This review starts with the basic features of quantal neurotransmitter release, then progresses to the current knowledge on how the active zones interact with each other along the same nerve terminal.
-
In several tauopathies such as Alzheimer's disease (AD), an increased incidence of seizures is observed. Tau, one of the major proteins implicated in AD pathology, is an important regulator of neural network excitability and might participate in the underlying epileptic cascade. However, the mechanisms underlying this relationship are not fully elucidated. ⋯ Also, age-related differences in susceptibility could be demonstrated for both genotypes. Identification and targeting of secondary diseases such as epilepsy, which aggravate dementia and lead to earlier institutionalization, is key. This study finds that tau pathology itself is sufficient to alter seizure susceptibility in a rodent model, indicating that the disease process is crucial in the emergence of epilepsy in patients with tauopathy.