Central Effects of Beta-Blockers May Be Due to Nitric Oxide and Hydrogen Peroxide Release Independently of Their Ability to Cross the Blood-Brain Barrier

Mitochondria are key cell organelles in that they are responsible for energy production and control many processes from signalling to cell death. The function of the mitochondrial electron transport chain is coupled with the production of reactive oxygen species (ROS) in the form of superoxide anion or hydrogen peroxide. As a result of the constant production of ROS, mitochondria are protected by highly efficient antioxidant systems. The rapidly changing levels of ROS in mitochondria, coupled with multiple essential cellular functions, make ROS apt for physiological signalling. Thus, mutations, environmental toxins and chronic ischaemic conditions could affect the mitochondrial redox balance and lead to the development of pathology. In long-living and non-mitotic cells such as neurons, oxidative stress induced by overproduction of mitochondrial ROS or impairment of the antioxidant defence results in a dysfunction of mitochondria and initiation of the cell death cascade. Mitochondrial ROS overproduction and changes in mitochondrial redox homeostasis have been shown to be involved in both a number of neurological conditions and a majority of neurodegenerative diseases. Here, we summarise the involvement of mitochondrial ROS in the mechanism of neuronal loss of major neurodegenerative disorders.

Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited.

Tanycytes are bipolar cells bridging the cerebrospinal fluid (CSF) to the portal capillaries and may link the CSF to neuroendocrine events. During the perinatal period a subpopulation of radial glial cells differentiates into tanycytes, a cell lineage sharing some properties with astrocytes and the radial glia, but displaying unique and distinct morphological, molecular, and functional characteristics. Four populations of tanycytes, alpha(1,2) and beta(1,2), can be distinguished. These subtypes express differentially important functional molecules, such as glucose and glutamate transporters; a series of receptors for neuropeptide and peripheral hormones; secretory molecules such as transforming growth factors, prostaglandin E(2), and the specific protein P85; and proteins of the endocytic pathways. This results in functional differences between the four subtypes of tanycytes. Thus, alpha(1,2) tanycytes do not have barrier properties, whereas beta(1,2) tanycytes do. Different types of tanycytes use different mechanisms to internalize and transport cargo molecules; compounds internalized via a clathrin-dependent endocytosis would only enter tanycytes from the CSF. There are also differences in the neuron-tanycyte relationships; beta(1,2) tanycytes are innervated by peptidergic and aminergic neurons, but alpha(1,2) tanycytes are not. Important aspects of the neuron-beta(1) tanycyte relationships have been elucidated. Tanycytes can participate in the release of gonadotropin-releasing hormone (GnRH) to the portal blood by expressing estrogen receptors, absorbing molecules from the CSF, and providing signal(s) to the GnRH neurons. Removal of tanycytes prevents the pulse of GnRH release into the portal blood, the peak of luteinizing hormone, and ovulation. The discovery in tanycytes of new functional molecules is opening a new field of research. Thus, thyroxine deiodinase type II, an enzyme generating triiodothyronine (T(3)) from thyroxine, appears to be exclusively expressed by tanycytes, suggesting that these cells are the main source of brain T(3). Glucose transporter-2 (GLUT-2), a low-affinity transporter of glucose and fructose, and ATP-sensitive K(+) channels are expressed by tanycytes, suggesting that they may sense CSF glucose concentrations.