Front Cell Neurosci
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Front Cell Neurosci · Jan 2015
ReviewAdapting for endocytosis: roles for endocytic sorting adaptors in directing neural development.
Proper cortical development depends on the orchestrated actions of a multitude of guidance receptors and adhesion molecules and their downstream signaling. The levels of these receptors on the surface and their precise locations can greatly affect guidance outcomes. ⋯ We will discuss the cell biology of regulated endocytosis and the impact on neural development. We focus our discussion on endocytic accessory proteins (EAPs) (such as numb and disabled) and how they regulate endocytosis and subsequent post-endocytic trafficking of their cognate receptors (such as Notch, TrkB, β-APP, VLDLR, and ApoER2).
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Front Cell Neurosci · Jan 2015
ReviewLost highway(s): barriers to postnatal cortical neurogenesis and implications for brain repair.
The genesis of the cerebral cortex is a highly complex and tightly-orchestrated process of cell division, migration, maturation, and integration. Developmental missteps often have catastrophic consequences on cortical function. Further, the cerebral cortex, in which neurogenesis takes place almost exclusively prenatally, has a very poor capacity for replacement of neurons lost to injury or disease. ⋯ Herein, we review corticogenesis from the context of regeneration and detail the strategies to promote neurogenesis, including interneuron transplants and glial reprogramming. Such strategies circumvent the "lost highways" which are critical for cortical development but are absent in the adult. These new approaches may provide for the possibility of meaningful clinical regeneration of elements of cortical circuitry lost to trauma and disease.
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Front Cell Neurosci · Jan 2015
ReviewSystemic inflammation and the brain: novel roles of genetic, molecular, and environmental cues as drivers of neurodegeneration.
The nervous and immune systems have evolved in parallel from the early bilaterians, in which innate immunity and a central nervous system (CNS) coexisted for the first time, to jawed vertebrates and the appearance of adaptive immunity. The CNS feeds from, and integrates efferent signals in response to, somatic and autonomic sensory information. The CNS receives input also from the periphery about inflammation and infection. ⋯ While SB manifestations are transient and self-limited, under states of persistent systemic inflammatory response the cognitive and behavioral changes can become permanent. For example, cognitive decline is almost universal in sepsis survivors, and a common finding in patients with systemic lupus erythematosus. Here, we review recent genetic evidence suggesting an association between neurodegenerative disorders and persistent immune activation; clinical and experimental evidence indicating previously unidentified immune-mediated pathways of neurodegeneration; and novel immunomodulatory targets and their potential relevance for neurodegenerative disorders.
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Front Cell Neurosci · Jan 2015
ReviewCellular and Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss - A Common Hereditary Deafness.
Hearing loss due to mutations in the connexin gene family, which encodes gap junctional proteins, is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2) mutations are responsible for ~50% of non-syndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. ⋯ However, the detailed cellular mechanisms underlying these pathological changes remain unclear. Also, little is known about specific mutation-induced pathological changes in vivo and little information is available for humans. Such further studies are urgently required.
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Gastrointestinal (GI) pain is a common clinical problem, for which effective therapy is quite limited. Sensations from the GI tract, including pain, are mediated largely by neurons in the dorsal root ganglia (DRG), and to a smaller extent by vagal afferents emerging from neurons in the nodose/jugular ganglia. Neurons in rodent DRG become hyperexcitable in models of GI pain (e.g., gastric or colonic inflammation), and can serve as a source for chronic pain. ⋯ The contribution of these changes to visceral pain remains to be determined. These results indicate that although visceral pain is unique, it shares basic mechanisms with somatic pain, suggesting that therapeutic approaches to both pain types may be similar. Future research in this field should include additional types of GI injury and also other types of visceral pain.