Progetto comune di ricerca

Metodi di microtomografia a raggi X in assorbimento e contrasto di fase per studiare il sistema limbico del cervello umano (ex-vivo)

Responsabili di progetto
Michela Fratini, Victor Asadchikov
Accordo
RUSSIA - RFBR-suspended - Russian Foundation for Basic Research
Bando
CNR/RFBR triennio 2018-2020 2018-2020
Dipartimento
Scienze fisiche e tecnologie della materia
Area tematica
Scienze fisiche e tecnologie della materia
Stato del progetto
Nuovo

Proposta di ricerca

Alzheimer's disease (AD) and presenile and senile dementia have conventionally been associated as a degeneration of the cerebral cortex; however, it is clear that other areas of the brain, notably the hippocampus and amygdala, are involved as well. These structures, together with others such as the fornix, cingulate gyrus, septal nuclei, and mammillary bodies, constitute the limbic system, which has been recognized as the anatomic substrate of memory, emotion, and learning. In this framework we propose to develop a multimodal approach, in collaboration with the Laboratory of X-ray reflectometry and small angle scattering, FSRC "Crystallography and Photonics" RAS, Moscow, based on advanAed X-ray 3D imaging technique and methods to study ex vivo human brain (HB) pineal glands (or epiphyses) and olfactory bulbs in subjects of different age (from 20 to 75). This study will allow for finding out more about the role of the human epiphysis and of human olfactory bulbs in the development of neural degenerative disorders, such as AD. The pineal gland, composed by pinealocytes (neurosecretory cells that secrete serotonin and melatonin), is a central structure in the circadian system, which produces melatonin under the control of the central clock, the suprachiasmatic nucleus (SCN) [1-4]. In addition, pineal calcications have been found in numerous animals and in humans [5]. Two major forms of pineal calcications have been observed: (i) polycrystalline complexes with dimensions of the order of hundreds of micrometers, often called mulberry-like structures hydroxyapatite or concretions, and (ii) small, well dened crystals having long dimensions of the order of 10-20 micron [5]. In addition, a new form of biomineralization has been studied in the pineal gland of the HD. It consists of small crystals that are less than 20 micron in length and that are completely distinct from the often observed mulberry-type hydroxyapatite concretions [5]. Calcium content and pineal concretions were studied in young and old Wistar rats [6]. This study suggested that pineal calcifications in rats could thus be an indicator of aging and/or of a degenerating state. In this framework, we want to investigate the neuronal network in different samples of a different age, looking for hydroxyapatite crystals in the pineal gland of the HB as an indicator of a degenerating state, using high resolution Synchrotron X-ray Phase contrast Tomography (XrPCT) (CNR group), X-ray absorption mode and topography mode (Russian team laboratory). In addition, we want to correlate the quantity of crystals both with the age of the subject and with pathological details. The olfactory bulb of the human brain is the primary olfactory nucleus of the brain. It terminates the processes of receptor neurons located in the olfactory epithelium. Recently, olfactory dysfunction has attracted the renewed interest of scientists, because olfactory dysfunction has the potential to be an early marker of neurodegenerative conditions, such as AD. Some studies confirmed that olfactory dysfunction was possibly one of the earliest clinical symptoms of AD [7]. However, the exact pathophysiological mechanism of olfactory dysfunction in AD is not fully understood [8]. In this framework, we want to study with high resolution XrPCT the spatial arrangement of neurons in the olfactory bulb, both in control samples and in samples with a reduced ability to perceive odors at different ages (20-75 years old). In particular, we have olfactory bulbs control samples and samples with loss ability to perceive odors. Because of the potentiality of XrPCT, it is possible to study and quantify the changes in the neuronal networks arrangements, as described in Bukreeva et al. [9]. This study will allow us to approach the advanced diagnosis of the development of AD, which is preceded by anosmia (loss of the ability to perceive odors). The results obtained by XrPC¼T will allow us to understand the role of human epiphysis and of human olfactory bulbs in the development and early diagnosis of a neural degenerative disease, like the AD. In addition we want to correlate our results with the results obtained by the absorption and topo-tomographic measurements, that will be carry out at the tomographic set-ups in the X-ray reflectometry and small angle scattering Lab, FSRC (Moscow).
ineal calcifications have been found in numerous
animals and in humans. They have been given numerous
names in the literature, including corpora arenacea,
acervuli, psammoma bodies, and brain sand [Welsh,
1985; Vigh et al., 1998]. Two major forms of pineal
calcifications have been observed: (i) polyc The samples will be provided by the collection of Institute of Human Morphology Russian Academy of Science. Samples are fixed in ethanol and will be embedded in agar-agar. We propose to perform the XRPCT experiment, to achieve an ex-vivo imaging of human olfactory bulbs and epiphyses at ESRF (ID17 beamline). We will collect 3D images of the neuronal network in the human olfactory bulbs. In addition, we expect to investigate the hydroxyapatite crystals and structure of soft tissue in human pineal glands at different ages, as an indicator of a degenerating state, using high resolution XrPCT. Furthermore, we want to correlate the quantity of crystals with the age of the subject and with pathological details.
1. Stephanie S. Erlich et al. Journal of Neurosurgery, 63, 321 (1985).
2. Wu, Y.-H. et al. Journal of Pineal Research, 38, 145 (2005).
3. Fokin E.I., et al . Arkh Patol. 68, 20 (2006)
4. Savel'ev SV, et al.. Arkh Patol.66(4):13, (2004).
5. Baconnier, S. et al. Bioelectromagnetics, 23: 488 (2002).
6. W. Humber et al, Cell and Tissue Research 263 , 593 (1991)
7. Serby M, Larson P, et al. Am J Psychiatry. 148(3), 357 (1991); & Devanand DP, et al. Am J Psychiatry. 157(9):1399 (2000).
8. Yong-ming Zou et al. Neuropsychiatr Dis Treat. 12: 869 (2016)
9. I. Brukreeva et al, Scientific Reports 7, 41054 (2017)

Obiettivi della ricerca

The aim of the project is the investigation of the human limbic system by means of X-ray imaging and tomography methods. For this goal we intend to develop a multimodal method based on a theoretical and experimental approach for preclinical applications. It is expected that at the end of the Project the results obtained will allow us to understand the role of the human epiphysis and of human olfactory bulbs in the development and early diagnosis of neural degenerative diseases, like the AD.
On these issues the collaboration between our group and the Institute of Laboratory of X-ray reflectometry and small angle scattering, FSRC "Crystallography and Photonics" RAS, Moscow, Russia, is at its first stage. This project would allow for its consolidation and would give the essential support the project needs. The collaboration with this Institute will allow us to profit from their experience in finding solutions for different imaging problems, which could greatly help our project.

Ultimo aggiornamento: 29/03/2024