TABLE 1.
Effect of histamine on neurons, microglia, astrocytes and mast cells during early brain development.
| Effect of histamine | References | |
| Neurons | Increased neural stem cell differentiation into GABAergic (adult) or glutamatergic (fetal) neurons via H1 receptors. | Molina-Hernández and Velasco, 2008; Bernardino et al., 2012 |
| Neural stem cell proliferation, apoptosis and decreased glial cell differentiation within the neuroepithelium of the cortex via H2 receptors. | Molina-Hernández and Velasco, 2008; Bernardino et al., 2012; Rodríguez-Martínez et al., 2012 | |
| Modulation of synaptic plasticity and neural circuits. | ||
| Increased ACh release from striatal cholinergic interneurons via H1 or H2 receptors. | Prast et al., 1999 | |
| Inhibition of GABA release from spiny projection neurons in the striatum via H3 receptors. | Ellender et al., 2011 | |
| Inhibition of glutamate release from synaptosomes. | Molina-Hernández et al., 2001 | |
| Inhibition of glutamate release from cortical afferents to striatum. | Doreulee et al., 2001; Ellender et al., 2011 | |
| Facilitating synaptic plasticity at corticostriatal synapses from the second postnatal week onward via H3 receptors. | Han et al., 2020 | |
| Facilitating long-term potentiation in the CA1 of the hippocampus via H1 and H2 receptors. | Brown et al., 1995; Dai et al., 2007; Haas et al., 2008; Chepkova et al., 2012 | |
| Microglia | Microglia express all four subsets of histamine receptor. | Dong et al., 2014a; Haas and Panula, 2016; Zhang et al., 2020 |
| Histamine can induce migration of microglia though H4 receptor activation. | Ferreira et al., 2012; Dong et al., 2014a; Fang et al., 2020; Zhang et al., 2020 | |
| Histamine can induce both pro- and anti-inflammatory response from microglia via H1 and H4 receptors. | Rocha et al., 2016; Lenz et al., 2018 | |
| Promote phagocytosis via H1 receptor activation and the production of reactive oxygen species and prostaglandin E2. | Frick et al., 2016 | |
| Hdc knockout (KO) mice have a normal number of microglia but with reduced ramifications, reduced IGF-1 expression and reduced expression of H4 receptor. | Frick et al., 2016 | |
| Pro-inflammatory microglial response to challenge with LPS was greater in Hdc KO mice. | Iida et al., 2015 | |
| H3 receptor mediated autocrine and paracrine signaling has also been shown to inhibit microglial chemotaxis and phagocytosis along with inhibiting LPS-induced cytokine production. | ||
| Astrocytes | The H1, H2, and H3 receptors have been consistently shown to be expressed on astrocytes. | Jurič et al., 2016; Karpati et al., 2018 |
| H3 receptor expression may be restricted to certain brain regions and may vary depending on the species that is studied. | ||
| Elicit glutamate release in an H1 receptor-dependent and concentration-dependent manner. | Hosli and Hosli, 1984; Hosli et al., 1984 | |
| Astrocytic Ca2+ signaling and subsequent astrocytic glutamate release was highly sensitive to histamine and concentration-dependent acting through the H1 receptor. Astrocytic cAMP levels increased in response to histamine, it remains unclear if and what role this has in gliotransmitter release. | Karpati et al., 2018 | |
| Histamine can act synergistically with pro-inflammatory cytokines such as IL-1 and IL-6 to modulate astrocytic release of neurotrophins such as NGF. | Lipnik-Štangelj and Čarman-Kržan, 2005; Lipnik-Stangelj and Carman-Krzan, 2006; Ales et al., 2008 | |
| Histamine selectively upregulates the expression of H1, H2, and H3 receptors, stimulated the synthesis of astrocytic GDNF and concentration-dependent inhibition of the production of pro-inflammatory cytokines, TNF-α and IL-1β. | Xu et al., 2018 | |
| Mast cells | Mast cells are a non-neuronal source of histamine that can be released upon degranulation. | Katoh et al., 2001; Haas et al., 2008 |
| Mast cell expression of H1 and H4 receptors is implicated in type 1 hypersensitivity reactions. However, their expression in brain mast cells is not confirmed. | Thangam et al., 2018 | |
| Co-cultures of mast cells with astrocytes has been shown to lead to the release of histamine and leukotrienes via CD40-CD40L interactions. | Kim et al., 2010 | |
| The mast cell degranulator, C48/80 can trigger hypothalamic microglial activation and the release of IL-6 and TNF-α. | Dong et al., 2017 | |
| Mast cell activation with estradiol stimulates microglial activation and subsequent prostaglandin release and that was associated with increased dendritic spine density and higher amounts of the dendritic spine protein, spinophilin. | Lenz et al., 2018 | |
| Mast cells strongly adhere to hippocampal neurons via cell adhesion molecule 1d. | Hagiyama et al., 2011 | |
| Neuropeptides released from neurites bind directly bind to mast cells, altering their activation state. | Kulka et al., 2008 | |
| Mast cell derived products may enter neurons via transgranulation, whereby mast cells are in direct contact with neurons and exocytosed mast cell granules are directly taken up by the adjacent neuron. | Wilhelm et al., 2005 |
ACh, acetylcholine; cAMP, cyclic adenosine monophosphate; GABA, gamma amino butyric acid; GDNF, glial-derived neurotrophic factor; H1, histamine 1; H2, histamine 2; H3, histamine 3; H4, histamine 4; Hdc KO, histamine decarboxylase knock out; IL-1β, interleukin-1 beta; IL-6, interleukin-6; LPS, lipopolysaccharide; NGF, nerve growth factor; NSC, neural stem cells; TNF-α, tumor necrosis factor alpha.