hiv protease Several mechanisms have been suggested to under
Several mechanisms have been suggested to underline the release of signalling molecules from astrocytes: reverse operation of glutamate transporters, volume-regulated anion channels, gap-junctional hemi channels, diffusional release through purinergic receptors and Ca2+-dependent exocytosis , , , , . There is a wide range of receptors expressed on astrocytes that are functionally coupled to changes in membrane potential or to intracellular signalling pathways such as activation of phospholipase C or adenylate cyclase. Both pathways are associated with the changes of intracellular concentration of Ca2+ ions which allow cell-to-cell communication, typical for astrocytes. Among identified receptors such as glutamatergic, GABAergic, adrenergic, purinergic, serotonergic, muscarinic, and peptidergic receptors, which have been found on protoplasmic, fibrous, or specialized (Bergmann glia, pituicytes, Müller glia) astrocytes in situ and in vivo , ; astrocytes express also different types of histamine receptors , , , , , , , , , . Expression of histamine receptors enables astrocytes to be an additional neuromodulatory system that encode and integrate incoming inputs of histamine from different sources. The aim of this review is to highlight our limited understanding of the involvement of histamine and histamine receptors on astroglial cell function.
The histaminergic system in CNS
Histamine actions in astrocytes Several histamine actions, associated with at least three histamine receptor subtypes, expressed on astrocytes, have been identified, and are related to major astrocyte functions like ion homeostasis, hiv protease metabolism, neurotransmitter clearance, neurotrophic activity and immune response (Fig. S1). H1R subtype has been found connected to most of the functions, regulated by histamine (Table 2). As described later in details, activation of H1R is involved in: (i) extracellular Ca2+ ions uptake which increases intracellular Ca2+ levels and thus influence Ca2+-dependent signalling , , , , , ; (ii) glucose allocation and histamine-induced glycogen breakdown via increased intracellular Ca2+ levels that contribute to glucose homeostasis , , , ; (iii) up-regulation of glutamate transporter 1 (GLT-1) expression and glutamate clearance by astrocytes, which result in neuroprotection against glutamate excitotoxicity , ; (iv) enhancing neurotrophic activity through the stimulation of neurotrophic factors release, like nerve growth factor (NGF) , ,  and neurotrophin-3 (NT-3) , and indirectly, through up-regulation of fibroblast growth factor-1 (FGF-1) receptor that enhance growth and differentiation ; (v) modulating immune response through the regulation of NGF release via cytokine interactions , , . H2R subtype is associated with histamine-induced glycogen breakdown via increases of cAMP formation that shows high importance of histamine in glucose homeostasis and energy supply in the central nerve system . H2R seems to be important also in neurotrophic activity through the stimulation of NT-3 synthesis  and, indirectly, through the enhancement of fibroblast growth factor-2 (FGF-2) stimulated cell proliferation . H3R subtype has also been found connected to neurotrophic activity of astrocytes, due to enforcement of expression and synthesis NT-3 in cultured astrocytes .
Acknowledgements We would like to thank Cvetka Blažek and Jožica Košir for assistance. Financial support from the Slovenian Agency for Research (ARRS) was received through grants ARRS-P3-019, P3-067, ARRS-J3-0024, ARRS-J3-081 and ARRS-J1-2014.
Forgotten memories may occasionally be recollected spontaneously. Even after the memories fade over time, the forgotten memories may persist latently in the brain. Therefore, reinforcement of positive modulators for retrieval of long-term memory may recover the ostensibly forgotten memories. Indeed, very few animal studies have successfully recovered retrograde amnesia in animals. Long-term treatment with a histone deacetylase inhibitor recovers forgotten fear memory . Optogenetic activation of memory engram neurons also restores forgotten fear memory . However, these studies needed long-term and/or highly invasive manipulation. Thus, a clinically applicable method that promotes the retrieval of forgotten long-term memories has not yet been established.