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Article ; Online: Emerging Lysosomal Functions for Photoreceptor Cell Homeostasis and Survival.

Santo, Manuela / Conte, Ivan

2021 Volume 11, Issue 1

Abstract: Lysosomes are membrane-bound cell organelles that respond to nutrient changes and are implicated in cell homeostasis and clearance mechanisms, allowing effective adaptation to specific cellular needs. The relevance of the lysosome has been elucidated in ... ...

Abstract	Lysosomes are membrane-bound cell organelles that respond to nutrient changes and are implicated in cell homeostasis and clearance mechanisms, allowing effective adaptation to specific cellular needs. The relevance of the lysosome has been elucidated in a number of different contexts. Of these, the retina represents an interesting scenario to appreciate the various functions of this organelle in both physiological and pathological conditions. Growing evidence suggests a role for lysosome-related mechanisms in retinal degeneration. Abnormal lysosomal activation or inhibition has dramatic consequences on photoreceptor cell homeostasis and impacts extensive cellular function, which in turn affects vision. Based on these findings, a series of therapeutic methods targeting lysosomal processes could offer treatment for blindness conditions. Here, we review the recent findings on membrane trafficking, subcellular organization, mechanisms by which lysosome/autophagy pathway impairment affects photoreceptor cell homeostasis and the recent advances on developing efficient lysosomal-based therapies for retinal disorders.
MeSH term(s)	Animals ; Autophagy ; Cell Survival ; Homeostasis ; Humans ; Lysosomes/metabolism ; Photoreceptor Cells/cytology ; Photoreceptor Cells/metabolism ; Retinal Diseases/pathology
Language	English
Publishing date	2021-12-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11010060
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Multidimensional Functional Profiling of Human Neuropathogenic

Frisari, Simone / Santo, Manuela / Hosseini, Ali / Manzati, Matteo / Giugliano, Michele / Mallamaci, Antonello

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: ... ...

Abstract	FOXG1
MeSH term(s)	Alleles ; Animals ; Brain/metabolism ; Cerebral Cortex/metabolism ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Gene Expression/genetics ; Gene Expression Regulation, Developmental/genetics ; Gene Frequency/genetics ; Humans ; Mice ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neurodevelopmental Disorders/genetics ; Neurogenesis ; Neurons/metabolism ; Primary Cell Culture ; Proof of Concept Study
Chemical Substances	FOXG1 protein, human ; Forkhead Transcription Factors ; Foxg1 protein, mouse ; Nerve Tissue Proteins
Language	English
Publishing date	2022-01-25
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/ijms23031343
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Intraventricular transplantation of engineered neuronal precursors for in vivo neuroarchitecture studies

Chiola, Simone / Santo, Manuela / Mallamaci, Antonello

Journal of visualized experiments. 2019 May 11, , no. 147

2019

Abstract: Gene control of neuronal cytoarchitecture is currently the subject of intensive investigation. Described here is a simple method developed to study in vivo gene control of neocortical projection neuron morphology. This method is based on (1) in vitro ... ...

Abstract	Gene control of neuronal cytoarchitecture is currently the subject of intensive investigation. Described here is a simple method developed to study in vivo gene control of neocortical projection neuron morphology. This method is based on (1) in vitro lentiviral engineering of neuronal precursors as "test" and "control" cells, (2) their co-transplantation into wild-type brains, and (3) paired morphometric evaluation of their neuronal derivatives. Specifically, E12.5 pallial precursors from panneuronal, genetically labeled donors, are employed for this purpose. They are engineered to take advantage of selected promoters and tetON/OFF technology, and they are free-hand transplanted into neonatal lateral ventricles. Later, upon immunofluorescence profiling of recipient brains, silhouettes of transplanted neurons are fed into NeurphologyJ open source software, their morphometric parameters are extracted, and average length and branching index are calculated. Compared to other methods, this one offers three main advantages: it permits achieving of fine control of transgene expression at affordable costs, it only requires basic surgical skills, and it provides statistically reliable results upon analysis of a limited number of animals. Because of its design, however, it is not adequate to address non cell-autonomous control of neuroarchitecture. Moreover, it should be preferably used to investigate neurite morphology control after completion of neuronal migration. In its present formulation, this method is exquisitely tuned to investigate gene control of glutamatergic neocortical neuron architecture. Taking advantage of transgenic lines expressing EGFP in other specific neural cell types, it can be re-purposed to address gene control of their architecture.
Keywords	animal use reduction ; animals ; brain ; branching ; computer software ; fluorescent antibody technique ; gene expression ; genes ; genetically modified organisms ; morphometry ; neurites
Language	English
Dates of publication	2019-0511
Size	p. e59242.
Publishing place	Journal of Visualized Experiments
Document type	Article
ISSN	1940-087X
DOI	10.3791/59242
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Intraventricular Transplantation of Engineered Neuronal Precursors for In Vivo Neuroarchitecture Studies.

Chiola, Simone / Santo, Manuela / Mallamaci, Antonello

Journal of visualized experiments : JoVE

2019 , Issue 147

Abstract	Gene control of neuronal cytoarchitecture is currently the subject of intensive investigation. Described here is a simple method developed to study in vivo gene control of neocortical projection neuron morphology. This method is based on (1) in vitro lentiviral engineering of neuronal precursors as "test" and "control" cells, (2) their co-transplantation into wild-type brains, and (3) paired morphometric evaluation of their neuronal derivatives. Specifically, E12.5 pallial precursors from panneuronal, genetically labeled donors, are employed for this purpose. They are engineered to take advantage of selected promoters and tetON/OFF technology, and they are free-hand transplanted into neonatal lateral ventricles. Later, upon immunofluorescence profiling of recipient brains, silhouettes of transplanted neurons are fed into NeurphologyJ open source software, their morphometric parameters are extracted, and average length and branching index are calculated. Compared to other methods, this one offers three main advantages: it permits achieving of fine control of transgene expression at affordable costs, it only requires basic surgical skills, and it provides statistically reliable results upon analysis of a limited number of animals. Because of its design, however, it is not adequate to address non cell-autonomous control of neuroarchitecture. Moreover, it should be preferably used to investigate neurite morphology control after completion of neuronal migration. In its present formulation, this method is exquisitely tuned to investigate gene control of glutamatergic neocortical neuron architecture. Taking advantage of transgenic lines expressing EGFP in other specific neural cell types, it can be re-purposed to address gene control of their architecture.
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Cell Movement ; Cerebral Ventricles/cytology ; Female ; Male ; Mice ; Neural Stem Cells/transplantation ; Neurites ; Neurons/physiology ; Tissue Engineering
Language	English
Publishing date	2019-05-11
Publishing country	United States
Document type	Journal Article ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/59242
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Spatial control of astrogenesis progression by cortical arealization genes.

Santo, Manuela / Rigoldi, Laura / Falcone, Carmen / Tuccillo, Mariacarmine / Calabrese, Michela / Martínez-Cerdeño, Verónica / Mallamaci, Antonello

Cerebral cortex (New York, N.Y. : 1991)

2022 Volume 33, Issue 6, Page(s) 3107–3123

Abstract: Sizes of neuronal, astroglial and oligodendroglial complements forming the neonatal cerebral cortex largely depend on rates at which pallial stem cells give rise to lineage-committed progenitors and the latter ones progress to mature cell types. Here, we ...

Abstract	Sizes of neuronal, astroglial and oligodendroglial complements forming the neonatal cerebral cortex largely depend on rates at which pallial stem cells give rise to lineage-committed progenitors and the latter ones progress to mature cell types. Here, we investigated the spatial articulation of pallial stem cells' (SCs) commitment to astrogenesis as well as the progression of committed astroglial progenitors (APs) to differentiated astrocytes, by clonal and kinetic profiling of pallial precursors. We found that caudal-medial (CM) SCs are more prone to astrogenesis than rostro-lateral (RL) ones, while RL-committed APs are more keen to proliferate than CM ones. Next, we assessed the control of these phenomena by 2 key transcription factor genes mastering regionalization of the early cortical primordium, Emx2 and Foxg1, via lentiviral somatic transgenesis, epistasis assays, and ad hoc rescue assays. We demonstrated that preferential CM SCs progression to astrogenesis is promoted by Emx2, mainly via Couptf1, Nfia, and Sox9 upregulation, while Foxg1 antagonizes such progression to some extent, likely via repression of Zbtb20. Finally, we showed that Foxg1 and Emx2 may be implicated-asymmetrically and antithetically-in shaping distinctive proliferative/differentiative behaviors displayed by APs in hippocampus and neocortex.
MeSH term(s)	Humans ; Infant, Newborn ; Astrocytes/metabolism ; Astrocytes/physiology ; Cell Differentiation/genetics ; Cell Differentiation/physiology ; COUP Transcription Factor I/genetics ; Gene Expression Regulation, Developmental/genetics ; Hippocampus/metabolism ; Hippocampus/physiology ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Neocortex/metabolism ; Neurogenesis/genetics ; Neurogenesis/physiology ; Neurons/metabolism ; Neurons/physiology ; Oligodendroglia/metabolism ; Oligodendroglia/physiology
Chemical Substances	COUP Transcription Factor I ; empty spiracles homeobox proteins ; FOXG1 protein, human ; Homeodomain Proteins ; NFIA protein, human ; SOX9 protein, human ; ZBTB20 protein, human ; NR2F1 protein, human
Language	English
Publishing date	2022-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhac264
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Covid-19 and the impacts on mental health: a sample from Rio Grande do Sul, Brazil.

Duarte, Michael de Quadros / Santo, Manuela Almeida da Silva / Lima, Carolina Palmeiro / Giordani, Jaqueline Portella / Trentini, Clarissa Marceli

Ciencia & saude coletiva

2020 Volume 25, Issue 9, Page(s) 3401–3411

Abstract: Pandemics such as that of COVID-19 affect a relatively large number of people and impose new rules and social habits on the world population. Information about the pandemic is constant in the media. Moreover, social distancing has been adopted in Brazil ... ...

Title translation	COVID-19 e os impactos na saúde mental: uma amostra do Rio Grande do Sul, Brasil.
Abstract	Pandemics such as that of COVID-19 affect a relatively large number of people and impose new rules and social habits on the world population. Information about the pandemic is constant in the media. Moreover, social distancing has been adopted in Brazil to prevent the spread of COVID-19, which may have economic and psychosocial consequences. This study aimed to verify the factors associated with indicators of mental disorders symptoms in residents of Rio Grande do Sul during the initial period of the social distancing policy. The study was approved by CONEP. There were 799 participants, aged between 18 and 75 years (M = 36.56; SD = 12.88); 82.7% were women, who answered a sociodemographic questionnaire of social distancing and the Self-Report Questionnaire (SRQ-20). The results indicated that having decreased income in the period, being part of the risk group and being more exposed to information about deaths and infected, are factors that can significantly harm mental health in this pandemic period. Investigating social determinants that contribute to greater vulnerability to the mental illness of the population is vital in the field of collective health for the planning of public actions and policies.
MeSH term(s)	Adolescent ; Adult ; Aged ; Brazil/epidemiology ; COVID-19 ; Coronavirus Infections/epidemiology ; Coronavirus Infections/psychology ; Female ; Health Policy ; Humans ; Income ; Male ; Mental Disorders/epidemiology ; Mental Health ; Middle Aged ; Pandemics ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/psychology ; Risk Factors ; Social Isolation/psychology ; Young Adult
Keywords	covid19
Language	Portuguese
Publishing date	2020-08-28
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	2078799-6
ISSN	1678-4561 ; 1413-8123
ISSN (online)	1678-4561
ISSN	1413-8123
DOI	10.1590/1413-81232020259.16472020
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: COVID-19 e os impactos na saúde mental

Duarte, Michael de Quadros / Santo, Manuela Almeida da Silva / Lima, Carolina Palmeiro / Giordani, Jaqueline Portella / Trentini, Clarissa Marceli

Ciência & Saúde Coletiva v.25 n.9 2020

uma amostra do Rio Grande do Sul, Brasil

2020

Abstract: Resumo As pandemias, como a da COVID-19, afetam uma quantidade relativamente grande de pessoas e impõem novas regras e hábitos sociais para a população mundial. As informações sobre a pandemia são constantes na mídia. Além disso, o distanciamento social ... ...

Abstract	Resumo As pandemias, como a da COVID-19, afetam uma quantidade relativamente grande de pessoas e impõem novas regras e hábitos sociais para a população mundial. As informações sobre a pandemia são constantes na mídia. Além disso, o distanciamento social foi adotado no Brasil como medida de prevenção da disseminação da COVID-19, o que pode ter consequências econômicas e psicossociais. Nesse contexto, o objetivo deste estudo foi verificar os fatores associados a indicadores de sintomas de transtornos mentais em residentes do Rio Grande do Sul, durante o período inicial da política de distanciamento social decorrente da pandemia da COVID-19. O estudo foi aprovado pelo CONEP. Participaram 799 pessoas, com idades entre 18 e 75 anos (M = 36,56; DP = 12,88), 82,7% mulheres, que responderam um questionário sociodemográfico, de distanciamento social e ao Self-Report Questionnaire (SRQ-20). Os resultados indicaram que ter renda diminuída no período, fazer parte do grupo de risco e estar mais exposto a informações sobre mortos e infectados, são fatores que podem provocar maior prejuízo na saúde mental nesse período pandemia. Investigar determinantes sociais que contribuem para maior vulnerabilidade ao adoecimento mental da população é importante no campo da saúde coletiva para o planejamento de ações e políticas públicas.
Keywords	Covid-19 ; Saúde mental ; Mídia ; Fatores de risco ; Pandemia ; covid19
Language	Portuguese
Publishing date	2020-09-01
Publisher	ABRASCO - Associação Brasileira de Saúde Coletiva
Publishing country	br
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: COVID-19 e os impactos na saúde mental: uma amostra do Rio Grande do Sul, Brasil./ COVID-19 e os impactos na saúde mental: uma amostra do Rio Grande do Sul, Brasil./ Covid-19 and the impacts on mental health: a sample from Rio Grande do Sul, Brazil

Duarte, Michael de Quadros / Santo, Manuela Almeida da Silva / Lima, Carolina Palmeiro / Giordani, Jaqueline Portella / Trentini, Clarissa Marceli

Cien Saude Colet

Abstract	Pandemics such as that of COVID-19 affect a relatively large number of people and impose new rules and social habits on the world population. Information about the pandemic is constant in the media. Moreover, social distancing has been adopted in Brazil to prevent the spread of COVID-19, which may have economic and psychosocial consequences. This study aimed to verify the factors associated with indicators of mental disorders symptoms in residents of Rio Grande do Sul during the initial period of the social distancing policy. The study was approved by CONEP. There were 799 participants, aged between 18 and 75 years (M = 36.56; SD = 12.88); 82.7% were women, who answered a sociodemographic questionnaire of social distancing and the Self-Report Questionnaire (SRQ-20). The results indicated that having decreased income in the period, being part of the risk group and being more exposed to information about deaths and infected, are factors that can significantly harm mental health in this pandemic period. Investigating social determinants that contribute to greater vulnerability to the mental illness of the population is vital in the field of collective health for the planning of public actions and policies.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #740429
Database	COVID19

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Article ; Online: Foxg1 Antagonizes Neocortical Stem Cell Progression to Astrogenesis.

Falcone, Carmen / Santo, Manuela / Liuzzi, Gabriele / Cannizzaro, Noemi / Grudina, Clara / Valencic, Erica / Peruzzotti-Jametti, Luca / Pluchino, Stefano / Mallamaci, Antonello

Cerebral cortex (New York, N.Y. : 1991)

2019 Volume 29, Issue 12, Page(s) 4903–4918

Abstract: Neocortical astrogenesis follows neuronogenesis and precedes oligogenesis. Among key factors dictating its temporal articulation, there are progression rates of pallial stem cells (SCs) towards astroglial lineages as well as activation rates of astrocyte ...

Abstract	Neocortical astrogenesis follows neuronogenesis and precedes oligogenesis. Among key factors dictating its temporal articulation, there are progression rates of pallial stem cells (SCs) towards astroglial lineages as well as activation rates of astrocyte differentiation programs in response to extrinsic gliogenic cues. In this study, we showed that high Foxg1 SC expression antagonizes astrocyte generation, while stimulating SC self-renewal and committing SCs to neuronogenesis. We found that mechanisms underlying this activity are mainly cell autonomous and highly pleiotropic. They include a concerted downregulation of 4 key effectors channeling neural SCs to astroglial fates, as well as defective activation of core molecular machineries implementing astroglial differentiation programs. Next, we found that SC Foxg1 levels specifically decline during the neuronogenic-to-gliogenic transition, pointing to a pivotal Foxg1 role in temporal modulation of astrogenesis. Finally, we showed that Foxg1 inhibits astrogenesis from human neocortical precursors, suggesting that this is an evolutionarily ancient trait.
MeSH term(s)	Animals ; Astrocytes/cytology ; Astrocytes/metabolism ; Cell Differentiation/physiology ; Forkhead Transcription Factors/metabolism ; Humans ; Mice ; Neocortex/embryology ; Neocortex/metabolism ; Nerve Tissue Proteins/metabolism ; Neural Stem Cells/cytology ; Neural Stem Cells/metabolism ; Neurogenesis/physiology
Chemical Substances	FOXG1 protein, human ; Forkhead Transcription Factors ; Foxg1 protein, mouse ; Nerve Tissue Proteins
Language	English
Publishing date	2019-02-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhz031
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Foxg1 Upregulation Enhances Neocortical Activity.

Tigani, Wendalina / Rossi, Moira Pinzan / Artimagnella, Osvaldo / Santo, Manuela / Rauti, Rossana / Sorbo, Teresa / Ulloa Severino, Francesco Paolo / Provenzano, Giovanni / Allegra, Manuela / Caleo, Matteo / Ballerini, Laura / Bozzi, Yuri / Mallamaci, Antonello

Cerebral cortex (New York, N.Y. : 1991)

2020 Volume 30, Issue 9, Page(s) 5147–5165

Abstract: Foxg1 is an ancient transcription factor gene orchestrating a number of neurodevelopmental processes taking place in the rostral brain. In this study, we investigated its impact on neocortical activity. We found that mice overexpressing Foxg1 in ... ...

Abstract	Foxg1 is an ancient transcription factor gene orchestrating a number of neurodevelopmental processes taking place in the rostral brain. In this study, we investigated its impact on neocortical activity. We found that mice overexpressing Foxg1 in neocortical pyramidal cells displayed an electroencephalography (EEG) with increased spike frequency and were more prone to kainic acid (KA)-induced seizures. Consistently, primary cultures of neocortical neurons gain-of-function for Foxg1 were hyperactive and hypersynchronized. That reflected an unbalanced expression of key genes encoding for ion channels, gamma aminobutyric acid and glutamate receptors, and was likely exacerbated by a pronounced interneuron depletion. We also detected a transient Foxg1 upregulation ignited in turn by neuronal activity and mediated by immediate early genes. Based on this, we propose that even small changes of Foxg1 levels may result in a profound impact on pyramidal cell activity, an issue relevant to neuronal physiology and neurological aberrancies associated to FOXG1 copy number variations.
MeSH term(s)	Animals ; DNA Copy Number Variations ; Electroencephalography ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Mice ; Neocortex/physiology ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Pyramidal Cells/metabolism ; Seizures/genetics ; Seizures/metabolism ; Up-Regulation
Chemical Substances	Forkhead Transcription Factors ; Foxg1 protein, mouse ; Nerve Tissue Proteins
Language	English
Publishing date	2020-05-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhaa107
Database	MEDical Literature Analysis and Retrieval System OnLINE

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