• 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • BGB324 synthesis While more detailed molecular studies on


    While more-detailed molecular studies on the mechanistic basis for heightened H3 receptor function in PAE rats are underway, we have also been exploring whether PAE alters other markers of histaminergic neurotransmission in affected brain regions. One question is whether PAE affected the number of histaminergic neurons or their projections to various brain regions. Prior studies in other laboratories have shown that PAE reduces the number of serotonergic neurons in the brainstem raphe nucleus (Sari and Zhou, 2004, Tajuddin and Druse, 1999, Zhou et al., 2002), as well as the innervation of serotonergic fibers to target brain regions (Sari et al., 2001, Zhou et al., 2002, Zhou et al., 2005, Zhou et al., 2001) and serotonin levels (Druse, Kuo, & Tajuddin, 1991). As histamine and serotonin are both indoleamine transmitters whose neural projection systems are developing during the prenatal period, we speculated that PAE might reduce the number of histamine neurons or the density of histaminergic projections to terminal fields in PAE-affected brain regions, such as the dentate gyrus or cerebral cortex. Central histaminergic neuron cell somata reside primarily in the tuberomammillary nucleus (TMN) of the ventral hypothalamus (Panula et al., 1984, Watanabe et al., 1984) and project throughout the entire central nervous system (Inagaki et al., 1988, Panula et al., 1989). These neurons reside in five clusters known as groups E1–E5, as described by Inagaki et al. (1990). Transmitter histamine is synthesized from the amino BGB324 synthesis precursor l-histidine by the rate-limiting enzyme histidine decarboxylase (HDC) (Lee, Fitzpatrick, Meier, & Fisher, 1981). HDC exists in multiple isoforms. A 74-kDa isoform is thought to be the proenzyme which undergoes caspase-dependent C-terminal modification to more active isoforms (Dartsch et al., 1998, Fennell and Fleming, 2014, Fleming et al., 2002), including a 54-kDa form. We have also questioned whether, in addition to histamine H3 receptors, PAE affected other histamine receptor subtypes in a manner that could diminish excitatory neurotransmission or synaptic plasticity at the perforant path-dentate granule cell synapse. Histamine H2 receptors are G-protein coupled receptors that activate adenylate cyclase (Baudry, Martres, & Schwartz, 1975). H2 receptors are present in many brain regions, including the dentate gyrus (Visuete et al., 1997). While there remains a limited understanding of the manner and extent to which H2 receptors modulate dentate granule cell responsiveness, H2 receptors do facilitate excitatory neurotransmission in hippocampal CA1 (Selbach, Brown, & Haas, 1997), as well as hippocampal CA3 pyramidal neurons (Diewald, Heimrich, Büsselberg, Watanabe, & Haas, 1997; Yanovsky & Haas, 1996). Further, dentate gyrus LTP is reduced in H2 receptor knockout mice (Dai et al., 2007). These studies provide reasoned speculation for a putative PAE-induced reduction in postsynaptic H2 receptor-mediated facilitation of granule cell responsiveness in PAE rats as another mechanistic consequence of PAE. In the present study, we employed immunohistochemical, biochemical, and radiohistochemical approaches to investigate whether PAE reduces: 1) histamine neuron number in the ventral hypothalamus, or 2) HDC protein expression levels; 3) histamine H2 receptor density, or 4) H2 receptor-effector coupling in nerve terminal regions.
    Materials and methods
    Discussion An earlier report characterizing voluntary drinking in our rat dams had examined 5% ethanol consumption at 1-h intervals (Savage et al., 2010). The results from this study suggested that ethanol consumption was relatively stable over the 4-h period each day. In the present study, we examined consumption during shorter intervals of time. The data in Fig. 1 confirmed that drinking was relatively stable during the last 3 h of a 4-h session, when measured at 30-min intervals. However, when measuring drinking at 15-min intervals during the first hour after the drinking tubes were introduced, we observed 3- to 4-fold greater ethanol consumption during the first 15 min of the 4-h session than in any subsequent interval. Importantly, this observation suggested to us that the best time to sample for peak maternal serum ethanol consumption in our paradigm was within 30 min of that peak ethanol consumption window. Accordingly, we have employed the 45-min time point after introduction of the ethanol drinking tubes when periodically measuring peak maternal serum ethanol concentration. This observation highlights the importance of knowing the ethanol consumption pattern when employing either voluntary or forced drinking paradigms to maximize the prospects of determining peak maternal serum ethanol concentration.