Abstract:
:Neurosteroids are cholesterol-based hormones that can be produced in the brain, independent of secretion from peripheral endocrine glands, such as the gonads and adrenals. A focus in our laboratory for over 25 years has been how production of the pregnane neurosteroid, allopregnanolone, is regulated and the novel (i.e., non steroid receptor) targets for steroid action for behavior. One endpoint of interest has been lordosis, the mating posture of female rodents. Allopregnanolone is necessary and sufficient for lordosis, and the brain circuitry underlying it, such as actions in the midbrain ventral tegmental area (VTA), has been well-characterized. Published and recent findings supporting a dynamic role of allopregnanolone are included in this review. First, contributions of ovarian and adrenal sources of precursors of allopregnanolone, and the requisite enzymatic actions for de novo production in the central nervous system will be discussed. Second, how allopregnanolone produced in the brain has actions on behavioral processes that are independent of binding to steroid receptors, but instead involve rapid modulatory actions via neurotransmitter targets (e.g., γ-amino butyric acid-GABA, N-methyl-D-aspartate- NMDA) will be reviewed. Third, a recent focus on characterizing the role of a promiscuous nuclear receptor, pregnane xenobiotic receptor (PXR), involved in cholesterol metabolism and expressed in the VTA, as a target for allopregnanolone and how this relates to both actions and production of allopregnanolone will be addressed. For example, allopregnanolone can bind PXR and knocking down expression of PXR in the midbrain VTA attenuates actions of allopregnanolone via NMDA and/or GABAA for lordosis. Our understanding of allopregnanolone's actions in the VTA for lordosis has been extended to reveal the role of allopregnanolone for broader, clinically-relevant questions, such as neurodevelopmental processes, neuropsychiatric disorders, epilepsy, and aging.
journal_name
Front Cell Neuroscijournal_title
Frontiers in cellular neuroscienceauthors
Frye CA,Koonce CJ,Walf AAdoi
10.3389/fncel.2014.00106subject
Has Abstractpub_date
2014-04-09 00:00:00pages
106issn
1662-5102journal_volume
8pub_type
杂志文章,评审abstract::Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, characterized by the progressive loss of motor neurons. The cause of this selective neuronal death is unknown, but transcriptional dysregulation is recently emerging as an important factor. The physical substrate for the regulation of the transc...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2013.00243
更新日期:2013-12-05 00:00:00
abstract::Heterogeneous populations of cerebellar Purkinje cells (PCs) are arranged into separate longitudinal stripes, which have different topographic afferent and efferent axonal connections presumably involved in different functions, and also show different electrophysiological properties in firing pattern and synaptic plas...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00513
更新日期:2019-01-08 00:00:00
abstract::The neuronal potassium-chloride co-transporter 2 [indicated thereafter as KCC2 (for protein) and Kcc2 (for gene)] is thought to play an important role in the post natal excitatory to inhibitory switch of GABA actions in the rodent hippocampus. Here, by studying hippocampi of wild-type (Kcc2(+/+)) and Kcc2 deficient (K...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2011.00023
更新日期:2011-11-01 00:00:00
abstract::Human brain organoids (mini-brains) consist of self-organized three-dimensional (3D) neural tissue which can be derived from reprogrammed adult cells and maintained for months in culture. These 3D structures manifest substantial potential for the modeling of neurodegenerative diseases and pave the way for personalized...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2020.00014
更新日期:2020-02-11 00:00:00
abstract::The blood brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB) form the barriers of the brain. These barriers are essential not only for the protection of the brain, but also in regulating the exchange of cells and molecules in and out of the brain. The choroid plexus (CP) epithelial cells and the ara...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00136
更新日期:2015-04-13 00:00:00
abstract::Nitric oxide (NO) is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS) which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream t...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00322
更新日期:2015-08-17 00:00:00
abstract::During the last decades it became increasingly evident that electrical synapses are capable of activity-dependent plasticity. However, measuring the actual strength of electrical transmission remains difficult. Usually changes in coupling strength can only be inferred indirectly from measures such as the coupling coef...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00043
更新日期:2019-02-12 00:00:00
abstract::Experimental and epidemiological data show that the severity and the duration of brain inflammation are attenuated in females compared to males. This attenuated brain inflammation is ascribed to 17β-estradiol. However, several studies suggest that 17β-estradiol is also endowed with proinflammatory properties. The aim ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00146
更新日期:2014-05-27 00:00:00
abstract::The neural extracellular matrix (ECM) is enriched with hyaluronic acid, chondroitin sulfate proteoglycans (CSPGs) and the glycoprotein tenascin-R, which play important roles in synaptic plasticity, as shown by studies of the CA1 region of the hippocampus. However, ECM molecules are strongly expressed in the CA2 region...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00149
更新日期:2018-05-30 00:00:00
abstract::The cerebellar cortex is remarkable for its organizational regularity, out of which task-related neural networks should emerge. In Purkinje cells, both complex and simple spike network patterns are evident in sensorimotor behavior. However, task-related patterns of activity in the granule cell layer (GCL) have been le...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/neuro.03.006.2009
更新日期:2009-07-20 00:00:00
abstract::Disturbances in mitochondrial biogenesis and bioenergetics, combined with neuroinflammation, play cardinal roles in the cognitive impairment during aging that is further exacerbated by transient cerebral ischemia. Both near-infrared (NIR) photobiomodulation (PBM) and Coenzyme Q10 (CoQ10) administration are known to st...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00074
更新日期:2019-03-19 00:00:00
abstract::In this review, I present and discuss the current understanding of aberrant electrical activity found in the ganglion cell layer (GCL) of rod-degenerated (rd) mouse retinas. The reported electrophysiological properties revealed by electrical imaging using high-density microelectrode arrays can be subdivided between sp...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2016.00025
更新日期:2016-02-08 00:00:00
abstract::Anabolic-androgenic steroids (AAS) are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately shou...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2013.00069
更新日期:2013-05-09 00:00:00
abstract::Interleukin-33 (IL-33) is a member of the interleukin-1 (IL-1) cytokine family and an extracellular ligand for the orphan IL-1 receptor ST2. Accumulated evidence shows that the IL-33/ST2 axis plays a crucial role in the pathogenesis of central nervous system (CNS) diseases and injury, including traumatic brain injury ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00095
更新日期:2018-04-25 00:00:00
abstract::The N-methyl-D-aspartate receptors (NMDARs) are part of a large multiprotein complex at the glutamatergic synapse. The assembly of NMDARs with synaptic proteins offers a means to regulate NMDAR channel properties and receptor trafficking, and couples NMDAR activation to distinct intracellular signaling pathways, thus ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2014.00160
更新日期:2014-06-10 00:00:00
abstract::[This corrects the article DOI: 10.3389/fncel.2018.00209.]. ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,已发布勘误
doi:10.3389/fncel.2019.00194
更新日期:2019-05-15 00:00:00
abstract::Abnormal accumulation of protein inclusions in motor neurons has been known as a major pathological change in amyotrophic lateral sclerosis (ALS). Increasing numbers of proteins including mutant Cu, Zn-superoxide dismutase (SOD1) have been identified as constituents of pathological inclusions in a form of insoluble fi...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2014.00083
更新日期:2014-03-18 00:00:00
abstract::Binge-drinking is the most prevalent form of alcohol abuse and while an early life history of binge-drinking is a significant risk factor for subsequent alcoholism and co-morbid affective disorders, relatively little is known regarding the biobehavioral impact of binge-drinking during the sensitive neurodevelopmental ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2016.00265
更新日期:2016-11-18 00:00:00
abstract::Stem cell research depends on extensive in vitro research. Poly-D-lysine (PDL) and polyornithine (PornT) are chemically synthesized amino acid chains promoting cell adhesion to solid substrates. Although, PDL and PornT are extensively used, there is no common agreement regarding the most optimal substance and its conc...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2016.00055
更新日期:2016-03-07 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-β (Aβ) plaques and the formation of neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. In response to Aβ and tau aggregates, microglia, the primary innate immune cells of the central nervous system (CNS), facilitate Aβ a...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2020.563446
更新日期:2020-09-18 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two progressive, fatal neurodegenerative syndromes with considerable clinical, genetic and pathological overlap. Clinical symptoms of FTD can be seen in ALS patients and vice versa. Recent genetic discoveries conclusively link the two diseases, ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00414
更新日期:2015-10-27 00:00:00
abstract::Axon growth inhibitors generated by reactive glial scars play an important role in failure of axon regeneration after CNS injury in mature mammals. Among the inhibitory factors, chondroitin sulfate proteoglycans (CSPGs) are potent suppressors of axon regeneration and are important molecular targets for designing effec...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2020.00174
更新日期:2020-07-02 00:00:00
abstract::Proper transport of the Parkinson's disease (PD) protein, α-synuclein (α-syn), is thought to be crucial for its localization and function at the synapse. Previous work has shown that defects in long distance transport within narrow caliber axons occur early in PD, but how such defects contribute to PD is unknown. Here...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00540
更新日期:2020-01-10 00:00:00
abstract::Chronic stress is a risk factor for the development of psychiatric disorders, some of which involve dysfunction of the prefrontal cortex (PFC). There is a higher prevalence of these chronic stress-related psychiatric disorders during adolescence, when the PFC has not yet fully matured. In the present work we studied t...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00442
更新日期:2015-11-12 00:00:00
abstract::A fundamental interest in circuit analysis is to parse out the synaptic inputs underlying a behavioral experience. Toward this aim, we have devised an unbiased strategy that specifically labels the afferent inputs that are activated by a defined stimulus in an activity-dependent manner. We validated this strategy in f...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2020.00114
更新日期:2020-05-12 00:00:00
abstract::The consistency, efficacy, and safety of cannabis-based medicines have been demonstrated in humans, leading to the approval of the first cannabis-based therapy to alleviate spasticity and pain associated with multiple sclerosis (MS). Indeed, the evidence supporting the therapeutic potential of cannabinoids for the man...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2020.00034
更新日期:2020-02-19 00:00:00
abstract::Neuroinflammation, characterized by chronic activation of the myeloid-derived microglia, is a hallmark of Alzheimer's disease (AD). Systemic inflammation, typically resulting from infection, has been linked to the progression of AD due to exacerbation of the chronic microglial reaction. However, the mechanism and the ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00397
更新日期:2018-11-06 00:00:00
abstract::There is growing recognition that fast mitochondrial transport in neurons is disrupted in multiple neurological diseases and psychiatric disorders. However, a major constraint in identifying novel therapeutics based on mitochondrial transport is that the large-scale analysis of fast transport is time consuming. Here w...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00435
更新日期:2015-11-03 00:00:00
abstract::It has been shown that matrix metalloproteinase 9 (MMP-9) is required for synaptic plasticity, learning and memory. In particular, MMP-9 involvement in long-term potentiation (LTP, the model of synaptic plasticity) in the hippocampus and prefrontal cortex has previously been demonstrated. Recent data suggest the role ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00073
更新日期:2015-03-11 00:00:00
abstract::Topographical and biochemical characteristics of the substrate are critical for neuronal differentiation including axonal outgrowth and regeneration of neural circuits in vivo. Contact stimuli and signaling molecules allow neurons to develop and stabilize synaptic contacts. Here we present the development, characteriz...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2012.00010
更新日期:2012-03-14 00:00:00