miR-129 Regulates Cell Viability in Alzheimer’s Disease Through Targeting Amyloid Precursor Protein (APP)

This study intends to explore miR-129’s effect on cell viability of Alzheimer’s disease by regulating the target gene APP. The hippocampal neurons were assigned into model group (MO group); mimetic group (SI group); inhibitor group (IN group) followed by analysis of hippocampal neuronal cell proliferation and activity, APP protein content, miR-129 expression and cell apoptosis by CCK-8 assay, Western blot method, MTT assay, qRT-PCR and flow cytometry. miR-129 expression of hippocampal neurons in IN group was lowest. Compared with IN and MO groups, SI group had significantly increased miR-129 level and reduced number of hippocampal neuron apoptosis (P < 0.05). Compared with IN group, MO group had significantly reduced cell apoptosis (P < 0.05). SI group had highest number of hippocampal neurons proliferation followed by IN group. SI group had highest OD value followed by MO group and IN group. The cell activity of SI group was higher than that of IN group and MO group (both P < 0.05). Compared with SI group, rat neuron activity in MO group was significantly higher than IN group (P < 0.05). The APP protein expression of hippocampal neuron cells in SI group was lowest followed by MO group and IN group (P < 0.05). In conclusion, the low miR-129 expression can inhibit the activity of hippocampal neurons possibly through up-regulation of APP protein content.

LiCl-induced sickness modulates spontaneous activity and response dynamics in rat gustatory cortex.

Gustatory Cortex (GC), a structure deeply involved in the making of consumption decisions, presumably performs this function by integrating information about taste, experiences, and internal states related to the animal’s health, such as illness. Here, we investigated this assertion, examining whether illness is represented in GC activity, and how this representation impacts taste responses and behavior. We recorded GC single-neuron activity and local field potentials (LFP) from healthy rats and (the same) rats made ill ( via LiCl injection). We show (consistent with the extant literature) that the onset of illness-related behaviors arises contemporaneously with alterations in spontaneous 7-12Hz LFP power at ~11 min following injection. This process was accompanied by reductions in single-neuron taste response magnitudes and discriminability, and with enhancements in palatability-relatedness – a result reflecting the collapse of responses toward a simple “good-bad” code arising in a specific subset of GC neurons. Overall, our data show that a state (illness) that profoundly reduces consumption changes basic properties of the sensory cortical response to tastes, in a manner that can easily explain illness’ impact on consumption.

A striatal plasticity that supports the long-term preservation of motor function in Parkinsonian mice.

Motor deficits of Parkinsons disease (PD) such as rigidity, bradykinesia and akinesia result from a progressive loss of nigrostriatal dopamine neurons. No therapies exist that slow their degeneration and the most effective treatments for the motor symptoms: L-dopa -the precursor to dopamine, and deep brain stimulation can produce dyskinesias and are highly invasive, respectively. Hence, alternative strategies targeted to slow the progression or delay the onset of motor symptoms are still highly sought. Here we report the identification of a long-term striatal plasticity mechanism that delays for several months, the onset of motor deficits in a mouse PD model. Specifically, we show that a one-week transient daily elevation of midbrain dopamine neuron activity during depletion preserves the connectivity of direct but not indirect pathway projection neurons. The findings are consistent with the balance theory of striatal output pathways and suggest a novel approach for treating the motor symptoms of PD.

Hyperexcitability and Homeostasis in Fragile X Syndrome

Fragile X Syndrome (FXS) is a leading inherited cause of autism and intellectual disability, resulting from a mutation in the FMR1 gene and subsequent loss of its protein product FMRP. Despite this simple genetic origin, FXS is a phenotypically complex disorder with a range of physical and neurocognitive disruptions. While numerous molecular and cellular pathways are affected by FMRP loss, there is growing evidence that circuit hyperexcitability may be a common convergence point that can account for many of the wide-ranging phenotypes seen in FXS. The mechanisms for hyperexcitability in FXS include alterations to excitatory synaptic function and connectivity, reduced inhibitory neuron activity, as well as changes to ion channel expression and conductance. However, understanding the impact of FMR1 mutation on circuit function is complicated by the inherent plasticity in neural circuits, which display an array of homeostatic mechanisms to maintain activity near set levels. FMRP is also an important regulator of activity-dependent plasticity in the brain, meaning that dysregulated plasticity can be both a cause and consequence of hyperexcitable networks in FXS. This makes it difficult to separate the direct effects of FMR1 mutation from the myriad and pleiotropic compensatory changes associated with it, both of which are likely to contribute to FXS pathophysiology. Here we will: (1) review evidence for hyperexcitability and homeostatic plasticity phenotypes in FXS models, focusing on similarities/differences across brain regions, cell-types, and developmental time points; (2) examine how excitability and plasticity disruptions interact with each other to ultimately contribute to circuit dysfunction in FXS; and (3) discuss how these synaptic and circuit deficits contribute to disease-relevant behavioral phenotypes like epilepsy and sensory hypersensitivity. Through this discussion of where the current field stands, we aim to introduce perspectives moving forward in FXS research.

Высокотемпературная сверхпроводниковая магнитная система для изучения нейронной активности

The paper describes a high-temperature superconducting magnetic system (HTS SMS) to equip an experimental stand intended for neuron activity researches under constant and low-frequency magnetic fields up to 1 T. The design of the magnetic system together with its electromagnetic and cryogenic parameters is briefly discussed. The test results of the preliminary experiments conducted in liquid nitrogen at 77 K for two interchangeable magnets are given. The first magnet was manufactured in the form of a double pancake coil wound with 4 mm high HTS tape. The second magnet was made of pure copper wire with no frame and was impregnated with a thermally conducting epoxy resin. The advantages of the HTS pancake coil were demonstrated in comparison with the cryo-resistive solenoid. Low energy consumption of the HTS magnetic system will allow conducting continuous non-invasive monitoring of biological objects in a magnetic field.

Comprehensive review on Alzheimer's Disease: Pathophysiology and its Treatment

Neurodegenerative disorders are marked by the loss of brain neuron activity, resulting in gradual cognitive impairment. The effects of neurodegenerative diseases are severe in terms of pathology and the cost of patient care. The aged, in general, are the most vulnerable. Alzheimer's disease (AD) is a brain ailment that causes cell degradation and is the leading cause of dementia, identified by a loss of thinking ability and independence in daily tasks. The amyloid cascade hypothesis, which attributes clinical signs/symptoms to an abundance of amyloid-beta (Aβ) peptides, enhanced deposition into amyloid plaques, and eventually neuronal destruction, is one theory for pathogenesis AD. The use of acetylcholinesterase inhibitors in AD treatment is based on their favorable effects on the disease's functional, cognitive and behavioral symptoms. However, their involvement in AD pathogenesis is uncertain. This comprehensive review will provide an overview of AD, including the pathophysiology, causes, treatments, and future treatment.

A neuronal prospect theory model in the brain reward circuitry

Prospect theory, arguably the most prominent theory of choice, is an obvious candidate for neural valuation models. How the activity of individual neurons, a possible computational unit, reflects prospect theory remains unknown. Here, we show with theoretical accuracy equivalent to that of human neuroimaging studies that single-neuron activity in four core reward-related cortical and subcortical regions represents the subjective valuation of risky gambles in monkeys. The activity of individual neurons in monkeys passively viewing a lottery reflects the desirability of probabilistic rewards, parameterized as a multiplicative combination of a utility and probability weighting functions in the prospect theory framework. The diverse patterns of valuation signals were not localized but distributed throughout most parts of the reward circuitry. A network model aggregating these signals reliably reconstructed risk preferences and subjective probability perceptions revealed by the animals' choices. Thus, distributed neural coding explains the computation of subjective valuations under risk.