Neuroscience
-
Gold nanoparticles (GNP) have emerged as an alternative to biomaterials in biomedical applications. Research has clearly demonstrated the relative safety and low toxicity of these molecules. However, the possible neuroprotective effect of GNP on the central nervous system (CNS) and its relationship with neurological and psychiatric disorders remain unclear. ⋯ GNP also prevented EtOH-induced increase in superoxide dismutase and catalase activities, suggesting a modulatory role of GNP in enzymatic antioxidant defenses. Our results showed that GNP was able to modulate the disruption of cholinergic and oxidative homeostasis in the brain of zebrafish. These findings indicate for the first time that zebrafish is an interesting perspective to investigate nanoparticles against disorders related to alcohol abuse.
-
Exposure to stress activates glucocorticoid receptors in the brain and facilitates the onset of multitude psychiatric disorders. It has been shown that FK506 binding protein 51 (FKBP5) expression increases during glucocorticoid receptor (GR) activation in various brain regions including the medial prefrontal cortex (mPFC). FKBP5 knockout (KO) mice are reported to be resilient to stress, however, it remains uninvestigated whether FKBP5 loss affects neurotransmission and if so, what the functional consequences are. ⋯ We found that GR activation significantly decreased excitatory neurotransmission in the mPFC, which was completely abolished upon FKBP5 deletion, in consistent with behavioral resilience observed in FKBP5 KO mice. Even though FKBP5 loss has minimal impact on neural excitability, we found that FKBP5 deletion distorts the excitatory/inhibitory balance in the mPFC. Our study suggests that FKBP5 deficiency leads to the mPFC insensitive to GR activation and provides a neurophysiological explanation for how FKBP5 deficiency may mediate stress resilience.
-
Nearly sixty years ago Fredrich Timm developed a histochemical technique that revealed a rich reserve of free zinc in distinct regions of the brain. Subsequent electron microscopy studies in Timm- stained brain tissue found that this "labile" pool of cellular zinc was highly concentrated at synaptic boutons, hinting a possible role for the metal in synaptic transmission. ⋯ Here, we delve into our current understanding of the many roles zinc plays in the brain, from influencing neurotransmission and sensory processing, to activating both pro-survival and pro-death neuronal signaling pathways. Moreover, we detail the many mechanisms that tightly regulate cellular zinc levels, including metal binding proteins and a large array of zinc transporters.
-
Circadian disruptions, along with altered affective and reward states, are commonly associated with psychiatric disorders. In addition to genetics, the enduring influence of environmental factors in programming neural networks is of increased interest in assessing the underpinnings of mental health. The duration of daylight or photoperiod is known to impact both the serotonin and dopamine systems, which are implicated in mood and reward-based disorders. ⋯ We next highlight how brain regions crucial for the serotoninergic system (i.e., dorsal raphe nucleus; DRN), and dopaminergic (i.e., nucleus accumbens; NAc and ventral tegmental area; VTA) system are intertwined in overlapping circuitry, and play influential roles in the pathology of mood and reward-based disorders. We then focus on human and animal studies that demonstrate the impact of circadian factors on the dopaminergic system. Lastly, we discuss how environmental factors such as circadian photoperiod can impact the neural circuits that are responsible for regulating affective and reward states, offering novel insights into the biological mechanisms underlying the pathophysiology, systems, and therapeutic treatments necessary for mood and reward-based disorders.
-
Every year the Alzheimer's Association publishes a report that provides facts and figures indicating the public health, social and economic impact of Alzheimer's disease (AD). In addition, there are a number of reviews on the disease for general readers. Also, at congresses, AD is analyzed at different but not always related levels, leading to an "elephant as seen by blind men situation" for many of the participants. The review presented herein seeks to provide readers with a holistic view of how AD develops from various perspectives: the whole human organism, brain, circuits, neurons, cellular hallmarks, and molecular level.