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Article: Estimation of cAMP binding in hippocampus CA1 field by a fluorescent probe.

Mucignat-Caretta, Carla / Caretta, Antonio

Frontiers in cell and developmental biology

2023 Volume 11, Page(s) 1267956

Abstract: The hippocampus is an allocortex structure involved in many complex processes, from memory formation to spatial navigation. It starts developing during prenatal life but acquires its adult functional properties around the peripubertal age, in both humans ...

Abstract	The hippocampus is an allocortex structure involved in many complex processes, from memory formation to spatial navigation. It starts developing during prenatal life but acquires its adult functional properties around the peripubertal age, in both humans and mice. Such prolonged maturation is accompanied by structural changes in microcircuitry and functional changes involving biochemical and electrophysiological events. Moreover, hippocampus undergoes plasticity phenomena throughout life. In murine rodents, the most relevant maturation steps in Cornu Ammonis 1 (CA1) hippocampal subfield occur during the third-fourth weeks of life. During this period, also the expression and localization of cAMP-dependent protein kinases (PKA) refines: many regulatory (R1A) PKA clusters appear, bound to the cytoskeleton. Here the binding characteristics of R1A are determined in CA1 by using confocal microscopy. Apparently, two binding sites are present with no evidence of cooperativity. Equilibrium dissociation constant is estimated around 22.9 nM. This value is lower from that estimated for R1A in soluble form, suggesting a different binding site conformation or accessibility in the tissue. The method described here may be useful to track the developmental changes in binding activity, which affects cAMP availability at selected intracellular microzones. Possible relations with functional consequences are discussed.
Language	English
Publishing date	2023-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2023.1267956
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Positive or negative environmental modulations on human brain development: the morpho-functional outcomes of music training or stress.

Mucignat-Caretta, Carla / Soravia, Giulia

Frontiers in neuroscience

2023 Volume 17, Page(s) 1266766

Abstract: In the last couple of decades, the study of human living brain has benefitted of neuroimaging and non-invasive electrophysiological techniques, which are particularly valuable during development. A number of studies allowed to trace the usual stages ... ...

Abstract	In the last couple of decades, the study of human living brain has benefitted of neuroimaging and non-invasive electrophysiological techniques, which are particularly valuable during development. A number of studies allowed to trace the usual stages leading from pregnancy to adult age, and relate them to functional and behavioral measurements. It was also possible to explore the effects of some interventions, behavioral or not, showing that the commonly followed pathway to adulthood may be steered by external interventions. These events may result in behavioral modifications but also in structural changes, in some cases limiting plasticity or extending/modifying critical periods. In this review, we outline the healthy human brain development in the absence of major issues or diseases. Then, the effects of negative (different stressors) and positive (music training) environmental stimuli on brain and behavioral development is depicted. Hence, it may be concluded that the typical development follows a course strictly dependent from environmental inputs, and that external intervention can be designed to positively counteract negative influences, particularly at young ages. We also focus on the social aspect of development, which starts
Language	English
Publishing date	2023-11-03
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2023.1266766
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Article ; Online: Processing of intraspecific chemical signals in the rodent brain.

Mucignat-Caretta, Carla

Cell and tissue research

2021 Volume 383, Issue 1, Page(s) 525–533

Abstract: In the rodent brain, the central processing of ecologically relevant chemical stimuli involves many different areas located at various levels within the neuraxis: the main and accessory olfactory bulbs, some nuclei in the amygdala, the hypothalamus, and ... ...

Abstract	In the rodent brain, the central processing of ecologically relevant chemical stimuli involves many different areas located at various levels within the neuraxis: the main and accessory olfactory bulbs, some nuclei in the amygdala, the hypothalamus, and brainstem. These areas allow the integration of the chemosensory stimuli with other sensory information and the selection of the appropriate neurohormonal and behavioral response. This review is a brief introduction to the processing of intraspecific chemosensory stimuli beyond the secondary projection, focusing on the activity of the relevant amygdala and hypothalamic nuclei, namely the medial amygdala and ventromedial hypothalamus. These areas are involved in the appropriate interpretation of chemosensory information and drive the selection of the proper response, which may be behavioral or hormonal and may affect the neural activity of other areas in the telencephalon and brainstem.Recent data support the notion that the processing of intraspecific chemical signals is not unique to one chemosensory system and some molecules may activate both the main and the accessory olfactory system. Moreover, both these systems have mixed projections and cooperate for the correct identification of the stimuli and selection of relevant responses.
MeSH term(s)	Animals ; Brain/physiology ; Rodentia
Language	English
Publishing date	2021-01-06
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	125067-x
ISSN	1432-0878 ; 0302-766X
ISSN (online)	1432-0878
ISSN	0302-766X
DOI	10.1007/s00441-020-03383-7
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Article ; Online: Not Only COVID-19: Involvement of Multiple Chemosensory Systems in Human Diseases.

Caretta, Antonio / Mucignat-Caretta, Carla

Frontiers in neural circuits

2022 Volume 16, Page(s) 862005

Abstract: Chemosensory systems are deemed marginal in human pathology. In appraising their role, we aim at suggesting a paradigm shift based on the available clinical and experimental data that will be discussed. Taste and olfaction are polymodal sensory systems, ... ...

Abstract	Chemosensory systems are deemed marginal in human pathology. In appraising their role, we aim at suggesting a paradigm shift based on the available clinical and experimental data that will be discussed. Taste and olfaction are polymodal sensory systems, providing inputs to many brain structures that regulate crucial visceral functions, including metabolism but also endocrine, cardiovascular, respiratory, and immune systems. Moreover, other visceral chemosensory systems monitor different essential chemical parameters of "milieu intérieur," transmitting their data to the brain areas receiving taste and olfactory inputs; hence, they participate in regulating the same vital functions. These chemosensory cells share many molecular features with olfactory or taste receptor cells, thus they may be affected by the same pathological events. In most COVID-19 patients, taste and olfaction are disturbed. This may represent only a small portion of a broadly diffuse chemosensory incapacitation. Indeed, many COVID-19 peculiar symptoms may be explained by the impairment of visceral chemosensory systems, for example, silent hypoxia, diarrhea, and the "cytokine storm". Dysregulation of chemosensory systems may underlie the much higher mortality rate of COVID-19 Acute Respiratory Distress Syndrome (ARDS) compared to ARDSs of different origins. In chronic non-infectious diseases like hypertension, diabetes, or cancer, the impairment of taste and/or olfaction has been consistently reported. This may signal diffuse chemosensory failure, possibly worsening the prognosis of these patients. Incapacitation of one or few chemosensory systems has negligible effects on survival under ordinary life conditions but, under stress, like metabolic imbalance or COVID-19 pneumonia, the impairment of multiple chemosensory systems may lead to dire consequences during the course of the disease.
MeSH term(s)	COVID-19 ; Humans ; Olfaction Disorders/diagnosis ; Smell ; Taste/physiology ; Taste Disorders/diagnosis
Language	English
Publishing date	2022-04-25
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2452968-0
ISSN	1662-5110 ; 1662-5110
ISSN (online)	1662-5110
ISSN	1662-5110
DOI	10.3389/fncir.2022.862005
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Article: Tumors of the Central Nervous System: An Update.

Mucignat-Caretta, Carla

Cancers

2020 Volume 12, Issue 9

Abstract: The brain may be affected by a variety of tumors of different grade, which originate from different cell types at distinct locations, thus impacting on the brain structure and function [ ... ]. ...

Abstract	The brain may be affected by a variety of tumors of different grade, which originate from different cell types at distinct locations, thus impacting on the brain structure and function [...].
Language	English
Publishing date	2020-09-03
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12092507
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Article: Are Multiple Chemosensory Systems Accountable for COVID-19 Outcome?

Caretta, Antonio / Mucignat-Caretta, Carla

Journal of clinical medicine

2021 Volume 10, Issue 23

Abstract: Chemosensory systems (olfaction, taste, trigeminus nerve, solitary chemoreceptor cells, neuroendocrine pulmonary cells, and carotid body, etc.) detect molecules outside or inside our body and may share common molecular markers. In addition to the ... ...

Abstract	Chemosensory systems (olfaction, taste, trigeminus nerve, solitary chemoreceptor cells, neuroendocrine pulmonary cells, and carotid body, etc.) detect molecules outside or inside our body and may share common molecular markers. In addition to the impairment of taste and olfaction, the detection of the internal chemical environment may also be incapacitated by COVID-19. If this is the case, different consequences can be expected. (1) In some patients, hypoxia does not trigger distressing dyspnea ("silent" hypoxia): Long-term follow-up may determine whether silent hypoxia is related to malfunctioning of carotid body chemoreceptors. Moreover, taste/olfaction and oxygen chemoreceptors may be hit simultaneously: Testing olfaction, taste, and oxygen chemoreceptor functions in the early stages of COVID-19 allows one to unravel their connections and trace the recovery path. (2) Solitary chemosensory cells are also involved in the regulation of the innate mucosal immune response: If these cells are affected in some COVID-19 patients, the mucosal innate immune response would be dysregulated, opening one up to massive infection, thus explaining why COVID-19 has lethal consequences in some patients. Similar to taste and olfaction, oxygen chemosensory function can be easily tested with a non-invasive procedure in humans, while functional tests for solitary chemosensory or pulmonary neuroendocrine cells are not available, and autoptic investigation is required to ascertain their involvement.
Language	English
Publishing date	2021-11-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10235601
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Article ; Online: Protein Kinase A Catalytic and Regulatory Subunits Interact Differently in Various Areas of Mouse Brain.

Mucignat-Caretta, Carla / Caretta, Antonio

International journal of molecular sciences

2020 Volume 21, Issue 9

Abstract: Protein kinase A (PKA) are tetramers of two catalytic and two regulatory subunits, docked at precise intracellular sites to provide localized phosphorylating activity, triggered by cAMP binding to regulatory subunits and subsequent dissociation of ... ...

Abstract	Protein kinase A (PKA) are tetramers of two catalytic and two regulatory subunits, docked at precise intracellular sites to provide localized phosphorylating activity, triggered by cAMP binding to regulatory subunits and subsequent dissociation of catalytic subunits. It is unclear whether in the brain PKA dissociated subunits may also be found. PKA catalytic subunit was examined in various mouse brain areas using immunofluorescence, equilibrium binding and western blot, to reveal its location in comparison to regulatory subunits type RI and RII. In the cerebral cortex, catalytic subunits colocalized with clusters of RI, yet not all RI clusters were bound to catalytic subunits. In stria terminalis, catalytic subunits were in proximity to RI but separated from them. Catalytic subunits clusters were also present in the corpus striatum, where RII clusters were detected, whereas RI clusters were absent. Upon cAMP addition, the distribution of regulatory subunits did not change, while catalytic subunits were completely released from regulatory subunits. Unpredictably, catalytic subunits were not solubilized; instead, they re-targeted to other binding sites within the tissue, suggesting local macromolecular reorganization. Hence, the interactions between catalytic and regulatory subunits of protein kinase A consistently vary in different brain areas, supporting the idea of multiple interaction patterns.
MeSH term(s)	Animals ; Brain/enzymology ; Cerebral Cortex/enzymology ; Corpus Striatum/enzymology ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinase Type I/genetics ; Cyclic AMP-Dependent Protein Kinase Type I/metabolism ; Cyclic AMP-Dependent Protein Kinase Type II/genetics ; Cyclic AMP-Dependent Protein Kinase Type II/metabolism ; Female ; Male ; Mice ; Organ Specificity ; Septal Nuclei/enzymology
Chemical Substances	Cyclic AMP (E0399OZS9N) ; Cyclic AMP-Dependent Protein Kinase Type I (EC 2.7.11.11) ; Cyclic AMP-Dependent Protein Kinase Type II (EC 2.7.11.11)
Language	English
Publishing date	2020-04-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21093051
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Age-Related In Vivo Structural Changes in the Male Mouse Olfactory Bulb and Their Correlation with Olfactory-Driven Behavior

Bontempi, Pietro / Ricatti, Maria Jimena / Sandri, Marco / Nicolato, Elena / Mucignat-Caretta, Carla / Zancanaro, Carlo

Biology (Basel). 2023 Feb. 28, v. 12, no. 3

2023

Abstract: Olfactory areas in mammalian brains are linked to centers that modulate behavior. During aging, sensitivity to odors decreases and structural changes are described in olfactory areas. We explored, in two groups of male mice (young and elderly, 6 and 19 ... ...

Abstract	Olfactory areas in mammalian brains are linked to centers that modulate behavior. During aging, sensitivity to odors decreases and structural changes are described in olfactory areas. We explored, in two groups of male mice (young and elderly, 6 and 19 months old, respectively), the link between the changes in olfactory bulb structure, detected with magnetic resonance imaging, and behavioral changes in a battery of tests on motor, olfactory, cognitive performance, and emotional reactivity. The behavioral pattern of elderly mice appears less anxious, being less scared by new situations. Additionally, the olfactory bulb of young and elderly mice differed in two variables derived from magnetic resonance imaging (fractional anisotropy and T2 maps). A random forest approach allowed to select the variables most predictive of the differences between young and elderly mice, and correlations were found between three behavioral variables indicative of anxious behavior and the two magnetic resonance variables mentioned above. These data suggest that in the living mouse, it is possible to describe co-occurring age-related behavioral and structural changes in the olfactory bulb. These data serve as a basis for studies on normal and pathological aging in the mouse, but also open new opportunities for in vivo human aging studies.
Keywords	anisotropy ; cognition ; elderly ; humans ; magnetism ; males ; mice ; olfactory bulb
Language	English
Dates of publication	2023-0228
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12030381
Database	NAL-Catalogue (AGRICOLA)

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Article: Cell Differentiation and Replication during Postnatal Development of the Murine First Molar

Balzano, Rudi / Stellini, Edoardo / Mucignat-Caretta, Carla

Biology. 2021 Aug. 14, v. 10, no. 8

2021

Abstract: Various signaling molecular pathways are involved in odontogenesis to promote cellular replication and differentiation. Tooth formation is controlled mainly by epithelial–mesenchymal interactions. The aim of this work was to investigate how cellular ... ...

Abstract	Various signaling molecular pathways are involved in odontogenesis to promote cellular replication and differentiation. Tooth formation is controlled mainly by epithelial–mesenchymal interactions. The aim of this work was to investigate how cellular replication and differentiation ensue during the formation of the murine first molar in postnatal ages until eruption, focusing on morphogenesis, odontoblast differentiation and cellular replication. Wild-type CD1 mice were examined from birth to weaning. Morphogenesis and interaction between developing epithelial and mesenchymal tissues were evaluated in hematoxylin–eosin and Gomori trichome stained sections. Immunohistochemistry for nestin, which mediates the differentiation of odontoblasts, especially their polarization and elongation, showed that this intermediate filament was apparent already at postnatal day P1 in the apical region of odontoblasts and progressed apically from cusp tips, while it was not present in epithelial tissues. The expression of nuclear antigen Ki-67 highlighted dividing cells in both epithelial and mesenchymal tissues at P1, while one week later they were restricted to the cementoenamel junction, guiding root elongation. The link between odontoblast maturation and cellular replication in the different tooth tissues is essential to understand the development of tooth shape and dimension, to outline mechanisms of tooth morphogenesis and possibly eruption.
Keywords	antigens ; cell differentiation ; epithelium ; immunohistochemistry ; mice ; morphogenesis ; postnatal development ; root growth ; trichomes
Language	English
Dates of publication	2021-0814
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology10080776
Database	NAL-Catalogue (AGRICOLA)

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Article: Cell Differentiation and Replication during Postnatal Development of the Murine First Molar.

Balzano, Rudi / Stellini, Edoardo / Mucignat-Caretta, Carla

Biology

2021 Volume 10, Issue 8

Abstract: Various signaling molecular pathways are involved in odontogenesis to promote cellular replication and differentiation. Tooth formation is controlled mainly by epithelial-mesenchymal interactions. The aim of this work was to investigate how cellular ... ...

Abstract	Various signaling molecular pathways are involved in odontogenesis to promote cellular replication and differentiation. Tooth formation is controlled mainly by epithelial-mesenchymal interactions. The aim of this work was to investigate how cellular replication and differentiation ensue during the formation of the murine first molar in postnatal ages until eruption, focusing on morphogenesis, odontoblast differentiation and cellular replication. Wild-type CD1 mice were examined from birth to weaning. Morphogenesis and interaction between developing epithelial and mesenchymal tissues were evaluated in hematoxylin-eosin and Gomori trichome stained sections. Immunohistochemistry for nestin, which mediates the differentiation of odontoblasts, especially their polarization and elongation, showed that this intermediate filament was apparent already at postnatal day P1 in the apical region of odontoblasts and progressed apically from cusp tips, while it was not present in epithelial tissues. The expression of nuclear antigen Ki-67 highlighted dividing cells in both epithelial and mesenchymal tissues at P1, while one week later they were restricted to the cementoenamel junction, guiding root elongation. The link between odontoblast maturation and cellular replication in the different tooth tissues is essential to understand the development of tooth shape and dimension, to outline mechanisms of tooth morphogenesis and possibly eruption.
Language	English
Publishing date	2021-08-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology10080776
Database	MEDical Literature Analysis and Retrieval System OnLINE

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