Differential expression of secretagogin immunostaining in the hippocampal formation and the entorhinal and perirhinal cortices of humans, rats, and mice

Abstract

Secretagogin (SCGN) is a recently discovered calcium‐binding protein belonging to the group of EF‐hand calcium‐binding proteins. SCGN immunostaining has been described in various regions of the human, rat and mouse brain. In these studies, it has been reported that, in general, the patterns of SCGN staining differ between rodents and human brains. These differences have been interpreted as uncovering phylogenetic differences in SCGN expression. Nevertheless, an important aspect that is not usually taken into account is that different methods are used for obtaining and processing brain tissue coming from humans and experimental animals. This is a critical issue since it has been shown that post‐mortem time delay and the method of fixation (i.e., perfused vs. nonperfused brains) may influence the results of the immunostaining. Thus, it is not clear whether differences found in comparative studies with the human brain are simply due to technical factors or species‐specific differences. In the present study, we analyzed the pattern of SCGN immunostaining in the adult human hippocampal formation (DG, CA1, CA2, CA3, subiculum, presubiculum, and parasubiculum) as well as in the entorhinal and perirhinal cortices. This pattern of immunostaining was compared with rat and mouse that were fixed either by perfusion or immersion and with different post‐mortem time delays (up to 5 hr) to mimic the way the human brain tissue is usually processed. We found a number of clear similarities and differences in the pattern of labeling among the human, rat, and mouse in these brain regions as well as between the different brain regions examined within each species. These differences were not due to the fixation.

Three-dimensional synaptic organization of the human hippocampal CA1 field

“…These values are much higher than the ones found in the present work for the human CA1 (Table 1). Such huge differences in synaptic density between humans and rodents -together with the above-mentioned divergences in the morphology and distribution of pyramidal cells in the SP of CA1 (18), as well as differences in other anatomical, genetic, molecular and physiological features (18,(21)(22)(23)(24)(25)-further support the notion that there are remarkable differences between the human and rodent CA1. These differences clearly need to be taken into consideration when making interpretations in translational studies comparing one species to another.…”

“…This great extent of SP represents a major difference with the rodent brain and other species. Indeed, important variances can be observed in the hippocampal neuroanatomy of humans compared to rodents (1,(18)(19)(20)(21). In the rat hippocampus, SP is around five cell bodies thick and neuronal somata are densely packed, being SR the layer that contributes the most to the total CA1 thickness.…”

“…The sampling procedure was approved by the Institutional Ethical Committee. Tissue from some of these human brains has been used in previous unrelated studies (18,21).…”

Three-dimensional synaptic organization of the human hippocampal CA1 field

“…This great extent of SP represents a major difference with the rodent brain and other species. Indeed, important variances can be observed in the hippocampal neuroanatomy of humans compared to rodents ( Amaral and Lavenex, 2007 ; Benavides-Piccione et al, 2020 ; Duvernoy, 2005 ; Slomianka et al, 2011 ; Tapia-González et al, 2020 ). In the rat hippocampus, SP is around five cell bodies thick and neuronal somata are densely packed, being SR the layer that contributes the most to the total CA1 thickness.…”

Multiple Origins of Secretagogin Expressing Cortical GABAergic Neuron Precursors in the Early Human Fetal Telencephalon

“…A ground-breaking study (Raju et al, 2018 ) demonstrated that expression of SCGN by cortical GABAergic neurons during development originating from the caudal and lateral ganglionic eminence (CGE and LGEs) at mid-gestation is a feature of human but not the mouse. Furthermore, SCGN expression is developmentally regulated and peaks before birth (Raju et al, 2018 ) with a very low density of interneuron-like SCGN+ cells detected in the neocortex of adult human post mortem brain by immunohistochemistry (Gartner et al, 2001 ; Tapia-González et al, 2020 ). However, a much higher density of both cell body and neuropil staining is observed in the human hippocampal and parahippocampal formations (Attems et al, 2007 ; Tapia-González et al, 2020 ).…”