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

Abstract

Serotonin receptor 1A and 2A positive cells in postmortem brainstems were demonstrated via immunohistochemistry in eight control age-matched elderly individuals and eight Alzheimer patients. The 5-HT1A positive cells were found in substantia nigra, pontile nucleus, and vagal as well as dorsal raphe nucleus, while 5-HT2A receptor positive cells were found in motor, sensory and spinal trigeminal nuclei, pontile nucleus, substantia nigra, and nucleus solitarius. A comparison in density of positive cells per unit area was made between control age-matched and Alzheimer individuals. Statistically significant differences (p ≤ 0.01) in density were observed in 5-HT1A cells in pontile, dorsal raphe, and vagal nuclei between control age-matched and Alzheimer, and in 5-HT2A positive cells in the sensory trigeminal nucleus, between control and Alzheimer. This de novo study indicated the presence of 5-HT1A and 5-HT2A receptor positive cells in the above nuclei of human brainstem and revealed differences in density between control age-matched and Alzheimer, indicating possible functional derangements in Alzheimer patients in these areas. In addition, colocalization studies indicated that 5-HT1A receptors were in cholinergic cells and gamma-aminobutyric acid positive fibers were linked to 5-HT2A receptor positive cells. It is hoped that understanding these two important 5-HT receptors and their localization might lead to advances in future therapeutic development.

Serotonin and its Receptors in the Human CNS with New Findings - A Mini Review

“…In human brainstem, 5-HT 1A and 5-HT 2A positive neurons were found mainly in the substantia nigra, pontine nucleus, the motor vagal and dorsal raphé nucleus, in the sensory, spinal V nuclei, and nucleus solitarius [22]. This strengthens the view that serotonergic related interactions are apparent in the motor, reticular, and sensory nuclei of the brainstem.…”

“…It has been recorded that at least some of these serotonergic neurons have -aminobutyric acid (GABA) and cholinergic inputs on their cell bodies or dendrites [22]. In our laboratory, we have found that a small percentage of serotonin neurons (no more than 30% of total neurons) also bear its own type of (serotonergic) receptors (1A and 2A) (Fig.…”

Repeated Clozapine Increases the Level of Serotonin 5-HT1AR Heterodimerization with 5-HT2A or Dopamine D2 Receptors in the Mouse Cortex

“…All required positive and negative controls were done indicating that used antibodies are specific (data not shown). Antibodies were chosen based on literature (Ramírez et al, 2009 ; Noga et al, 2009 ; Yeung et al, 2010 ; Merlo et al, 2011 ; Hooper et al, 2016 ; Xiao et al, 2016 ). Moreover, we checked the specificity of antibodies by Western Blot, where different levels of receptors protein in different mouse brain structures were observed (data not shown).…”

The role of serotonin in respiratory function and dysfunction

“…Autopsy of dementia patients reveal normal numbers of 5-HT neurons in the dorsal raphe nuclei (Hendricksen et al, 2004) but abnormal density of 5-HT 1A and 5-HT 2A R (Yeung et al, 2010) in pons and medulla. In the cortex of AD patients 5-HT 1A R alteration was found in correlation with aggressive behaviours (Lai et al, 2003) and a reduced density of 5-HT 4 R expression connected to hyperphagia (Tsang et al, 2010).…”