Distribution of histamine‐, 5‐hydroxytryptamine‐, and tyrosine hydroxylase‐immunoreactive neurons and nerve fibers in developing rat brain

Abstract

Although the general patterns of the developing histaminergic system in the rat brain are known, no comparative studies between the development of the brain histaminergic system and the development of other neuroactive substances have yet been published. Interestingly, separate immunohistochemical studies on the development of the 5-HT system and on the catecholaminergic system in the rat imply common features in the different aminergic systems. Therefore, the spatial distribution of histamine-immunoreactive (HA-ir) neurons and nerve fibers was compared to the distribution of 5-hydroxytryptamine (5-HT)-, and tyrosine hydroxylase-immunoreactive (TH-ir) ones in the developing rat brain between embryonic days 12 (E12) and 20 (E20) by using a double-immunostaining method. The high-pressure liquid chromatography (HPLC) fluorometric method was used for determination of histamine concentration in different brain regions during the same period of development and synthetic oligonucleotide probes complementary to the rat histidine decarboxylase (HDC) to determine the origin of HA in the brain during the development with in situ hybridization. The immunohistochemical results revealed co-localization of HA and 5-HT within a subgroup of cells in the developing raphe nuclei between E14 and E18. From E18 onwards HA immunoreactivity started to gradually disappear from the rhombencephalon, and was totally abolished by E20, while 5-HT-ir cells continued to establish their adult positions. No significant colocalization of HA and TH immunoreactivities was detected. The biochemical results were in agreement with the immunohistochemical ones and confirmed that histamine detected in the early developing brain is authentic. A positive in situ hybridization signal for HDC was detected in a small area in the ventrolateral pons in the same areas as HA- and HDC-ir cell bodies at E16, suggesting that at least some HA may be synthesized locally. These results confirm that HA is one of the first neurotransmitters to appear in the developing brain. In addition, the transient co-localization of HA and 5-HT immunoreactivities and the transient HDC expression at E16 within the developing pontine raphe nuclei may imply an interesting and a more general role for HA in modification of brain development.

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

“…From embryonic day 17, strong expression is found in superficial layers of the cortical plate and ventral hypothalamus. It is noteworthy that in rodents there is a distinct transient fetal histaminergic system in the raphe neurons (Auvinen and Panula, 1988;Vanhala et al, 1994), which implies that the fetal expression of H 2 receptor mRNA may be functional during brain development.…”

In situ detection of H1-receptor mRNA and absence of apoptosis in the transient histamine system of the embryonic rat brain

“…Histamine concentration remains high throughout E14-17 (Pearce and Schanberg, 1969;Tuomisto and Panula, 1991;Vanhala et al, 1994) but gradually decreases toward the birth. This phenomenon reflects a dramatic decrease of histamine concentration in the pontine region and the disappearance of the transient histamine system by E20 (Vanhala et al, 1994). The appearance of histaminecontaining mast cells in the developing brain starting at E18 (Auvinen and Panula, 1988) and continuing postnatally, results largely in another peak in brain histamine concentration on the fifth postnatal day (P5; Pearce and Schanberg, 1969;Ferrer et al, 1979;Tuomisto and Panula, 1991), whereafter the concentration decreases to that of adult levels during the first postnatal weeks.…”

“…At the same time, from E14 until E18, histamine-immunoreactive (ir) cell bodies and nerve fibers form a relatively large population in the developing mesencephalon and rhombencephalon reminiscent of the developing serotonergic system in the spatiotemporal distribution (Wallace and Lauder, 1983;Vanhala et al, 1994). Histamine concentration remains high throughout E14-17 (Pearce and Schanberg, 1969;Tuomisto and Panula, 1991;Vanhala et al, 1994) but gradually decreases toward the birth. This phenomenon reflects a dramatic decrease of histamine concentration in the pontine region and the disappearance of the transient histamine system by E20 (Vanhala et al, 1994).…”

“…Between E14 and E18, histamine-ir nerve fibers originating from the transient histamine-ir cell group in the raphe nuclei can be transiently detected in the pons, traversing through the ventral tegmental area and within the median forebrain bundle and prominently in the optic tract (Auvinen and Panula, 1988;Vanhala et al, 1994). The first histaminergic nerve fibers reach the frontal and the parietal cortex also very early, at E15 (Auvinen and Panula, 1988), which is earlier than in other monoaminergic systems (Specht et al, 1981;Lidov and Molliver, 1982).…”

“…Very high concentrations of histamine can be measured in the developing rat mesencephalon and rhombencephalon prenatally, at embryonic day (E) 13-17 (Vanhala et al, 1994) with a sensitive fluorometric high pressure liquid chromatography (HPLC) method (Yamatodani et al, 1985;Yamatodani, 1991). At the same time, from E14 until E18, histamine-immunoreactive (ir) cell bodies and nerve fibers form a relatively large population in the developing mesencephalon and rhombencephalon reminiscent of the developing serotonergic system in the spatiotemporal distribution (Wallace and Lauder, 1983;Vanhala et al, 1994).…”