Postnatal changes in the expressions of serotonin 1A, 1B, and 2A receptors in ten brain stem nuclei of the rat: implication for a sensitive period

Abstract

A critical period in respiratory network development occurs in the rat around postnatal days (P)12–13, when abrupt neurochemical, metabolic, and physiological changes were evident. As serotonin (5-HT) and its receptors are involved in respiratory modulation, and serotonergic abnormality is implicated in Sudden Infant Death Syndrome, we hypothesized that 5-HT receptors are significantly down-regulated during the critical period. This was documented recently for 5-HT2AR in several respiratory nuclei. The present study represents a comprehensive analysis of postnatal development of 5-HT1AR and 5-HT1BR in ten brain stem nuclei and 5-HT2AR in six nuclei not previously examined. Optical densitometric analysis of immunohistochemically-reacted neurons from P2 to P21 indicated four developmental patterns of expression: 1) Pattern I: a high level of expression at P2–P11, an abrupt and significant reduction at P12, followed by a plateau until P21 (5-HT1AR and 5-HT1BR in raphé magnus [RM], raphé obscurus [ROb], raphé pallidus [RP], pre-Bötzinger complex [PBC], nucleus ambiguus [Amb], and hypoglossal nucleus [XII; 5-HT1AR only]). 2) Pattern II: a high level at P2–P9, a gradual decline from P9 to P12, followed by a plateau until P21 (5-HT1AR and 5-HT1BR in the retrotrapezoid nucleus [RTN]/parafacial respiratory group [pFRG]). 3) Pattern III: a high level at P2–P11, followed by a gradual decline until P21 (5-HT1AR in the ventrolateral subnucleus of solitary tract nucleus [NTSVL] and the non-respiratory cuneate nucleus [CN]). 4) Pattern IV: a relatively constant level maintained from P2 to P21 (5-HT1AR in the commissural subnucleus of solitary tract nucleus [NTSCOM]; 5-HT1BR in XII, NTSVL, NTSCOM, and CN; and 5-HT2AR in RM, ROb, RP, RTN/pFRG, NTSVL, and NTSCOM). Thus, a significant reduction in the expression of 5-HT1AR, 5-HT1BR, and 5-HT2AR in multiple respiratory-related nuclei at P12 is consistent with reduced serotonergic transmission during the critical period, thereby rendering the animals less able to respond adequately to ventilatory distress.

Localization of 5-HT1A and 5-HT2A positive cells in the brainstems of control age-matched and Alzheimer individuals

“…This is something we should note with care. Related studies on receptors 5-HT1A and 1B on the brainstem nuclei have been documented in the postnatal rat: The positive sites were mainly in the raphe nucleus, nucleus ambiguus, hypoglossal nucleus, and the reticular, and solitary nucleus (Liu and Wong-Riley 2010). In this adult human study, we have additional positive locations, e.g., pontile nucleus, vagal nucleus, and trigeminal nucleus.…”

Salt sensitivity of the morphometry of Artemia franciscana during development: A demonstration of 3-D critical windows

“…For example, during development, periods may exist when the emerging phenotype of an animal is particularly plastic or susceptible to an environmental stressor -these periods are often termed 'critical windows' or 'sensitive periods' (Pinkerton and Joad, 2000;Rice and Barone, 2000;van Aerle et al, 2002;Chan and Burggren, 2005;Hogan et al, 2008;Burggren and Reyna, 2011;Burggren et al, 2014;Burggren and Mueller, 2015). Across a range of animal taxa, from invertebrates to mammals, exposure to environmental, chemical or pharmacological stressors at certain time points of development is utilized to detect and understand critical windows during development (Green et al, 1986;Dzialowski et al, 2002;Maack and Segner, 2004;Chan and Burggren, 2005;Liu and Wong-Riley, 2010;Yuan et al, 2011;Tate et al, 2015). Phenotypic changes during critical windows have potential long-term implications for the animal's biology, ranging from molecular to morphological and physiological levels.…”

Developmental nicotine exposure adversely effects respiratory patterning in the barbiturate anesthetized neonatal rat

“…This age range encompasses both preterm and very early post-natal periods of the human infant. Although the risk for respiratory instability and SIDS is predicted to peak at P12-13, corresponding to the "critical period" in rat brainstem development (Liu et al, 2006;Liu and Wong-Riley, 2010;Wong-Riley and Liu, 2008), the present findings serve as proof of concept and demonstrate the potential to apply ACF in detection of respiratory disturbances at the very earliest development stages.…”