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Papers by Gian-Luca Ferri
Cells, 2022
The authors want to notify that they have made the following changes to the author list of the pa... more The authors want to notify that they have made the following changes to the author list of the paper [...]
Italian journal of anatomy and embryology, 2017
APECED (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Distrophy) is a rare autosomal reces... more APECED (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Distrophy) is a rare autosomal recessive disorder. We previously found that sera samples from 9/14 patients revealed autoantibodies (Auto-Abs) reacting with cerebellum (GABAergic cells, n=5) and substantia nigra (SN; dopaminergic cells, n=5) [1]. Follow-up of the large majority of these patients was perfomed at least 10 years after the previous investigation. Indeed, on these patients, and on control age-matched subjects (n=14), we performed brain examinations using an MRI scanner. Obtained images were used to evaluate the volumes of white and gray matter (W.M and G.M., respectively) as well as the ventricles (III and IV). In addition, we used immunohistochemistry (IHC) on tissues from rat brain (after perfusion with 4% paraformaldehyde) in order to confirm the previous immunoreactivities or found new Auto-Abs cell targets. The brain MR revealed a reduction of G.M (p = 0.042) and cerebellum (p = 0.0012), and an increase of...
Italian journal of anatomy and embryology, 2012
VGF peptides are selectively expressed in neurons and endocrine cells, and were found to be modul... more VGF peptides are selectively expressed in neurons and endocrine cells, and were found to be modulated in the cerebrospinal fluid of patients affected by certain neurodegenerative diseases, as well as decreased in parietal cortex from Parkinson’s disease (PD) patients. We used Sprague-Dowley rats treated with 6-hydroxydopamine (6-OHDA) in the right hemisphere to destroy dopaminergic neurons. Samples of cortex, hypothalamus and substantia nigra (SN) were collected. Human blood samples were obtained from patients affected by PD (n=6) and age-matched controls (n=6, not affected by neurodegenerative disease/s). Specific ELISA were used, as appropriate for rat tissues and human plasma. These were set up with antibodies to: (i) the C- and N-terminal sequences of human / rat VGF precursor, and: (ii) the internal cleaved products: PGH-, TLQP-, and NERP-1 peptides. Preliminary immunohistochemical experiments (IHC) were carried out on control rats, using antibodies to the same VGF-peptides lis...
Development, 1996
During migration and for about 2 days after their arrival in the gonadal ridges, primordial germ ... more During migration and for about 2 days after their arrival in the gonadal ridges, primordial germ cells (the embryonic precursors of gametes of the adult animal) proliferate actively. Certain growth factors, such as stem cell factor and leukemia inhibitory factor, seem to be essential for survival, proliferation and possibly differentiation of mouse primordial germ cell in vivo and/or in vitro. Similarly, increase in intracellular cAMP is followed by a marked enhancement of primordial germ cell proliferation, at least in culture. In the present study, we show that pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP-38), two neuropeptides of the secretin-glucagon-vasoactive intestinal polypeptide-GH-releasing hormone family, stimulate in vitro proliferation of mouse primordial germ cells, bind to primordial germ cells and gonadal somatic cells (possibly to type I PACAP receptor) and activate adenylate cyclase in the same cells. Moreover, PACAP-like immunoreactivity...
Neuropsychopharmacology, 2020
BMJ Open, 2020
IntroductionSevere psychiatric disorders are typically associated with a significant reduction in... more IntroductionSevere psychiatric disorders are typically associated with a significant reduction in life expectancy compared with the general population. Among the different hypotheses formulated to explain this observation, accelerated ageing has been increasingly recognised as the main culprit. At the same time, telomere shortening is becoming widely accepted as a proxy molecular marker of ageing. The present study aims to fill a gap in the literature by better defining the complex interaction/s between inflammation, age-related comorbidities, telomere shortening and gut microbiota in psychiatric disorders.Methods and analysisA cross-sectional study is proposed, recruiting 40 patients for each of three different diagnostic categories (bipolar disorder, schizophrenia and major depressive disorder) treated at the Section of Psychiatry and at the Unit of Clinical Pharmacology of the University Hospital Agency of Cagliari (Italy), compared with 40 age-matched and sex-matched non-psychia...
European Neuropsychopharmacology, 2019
International Journal of Molecular Sciences, 2019
In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential ... more In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential biomarker for dementia with Lewy bodies (DLB). Here, we extended the study of VGF by comparing levels in cerebrospinal fluid (CSF) from 44 DLB patients, 20 Alzheimer’s disease (AD) patients, and 22 cognitively normal controls selected from the Amsterdam Dementia Cohort. CSF was analyzed using two orthogonal analytical methods: (1) In-house-developed quantitative ELISA and (2) selected reaction monitoring (SRM). We further addressed associations of VGF with other CSF biomarkers and cognition. VGF levels were lower in CSF from patients with DLB compared to either AD patients or controls. VGF was positively correlated with CSF tau and α-synuclein (0.55 < r < 0.75), but not with Aβ1-42. In DLB patients, low VGF levels were related to a more advanced cognitive decline at time of first presentation, whereas high levels of VGF were associated with steeper subsequent longitudinal cognitive...
The TLQP-21 peptide peripherally potentiates glucose-stimulated insulin secretion. The aim of thi... more The TLQP-21 peptide peripherally potentiates glucose-stimulated insulin secretion. The aim of this study was to investigate a possible endocrine mechanism through which TLQP-21 increases the insulin secretion. Using an antibody specific for the common N-terminal portion of the TLQP peptides, we studied pancreas and plasma of mice subjected to intraperitoneal glucose load, by immunohistochemistry and immunosorbent assay (ELISA), alone or coupled to High Performance Liquid Chromatography (HLPC). Mice underwent a period of starvation hence have received a glucose load, or saline, and were sacrificed 30 or 120 minutes later. In normal endocrine pancreas, the TLQP-antiserum stained either peripheral or central cells. Interestingly, 30 min after a glucose load, TLQP immunostaining was disappeared in pancreas and, when analysed by ELISA, the TLQP-levels started to increase in plasma reaching peak concentration at 120 min. (controls vs. 30 and 120 min.: p<0.05 and…
International journal of molecular sciences, Jan 3, 2017
This review summarized different studies reporting the presence of autoantibodies reacting agains... more This review summarized different studies reporting the presence of autoantibodies reacting against cells of the pituitary (APAs) and/or hypothalamus (AHAs). Both APAs and AHAs have been revealed through immunofluorescence using different kinds of substrates. Autoantibodies against gonadotropic cells were mainly found in patients affected by cryptorchidism and hypogonadotropic hypogonadism while those against prolactin cells were found in different kinds of patients, the majority without pituitary abnormalities. APAs to growth hormone (GH) cells have been associated with GH deficiency while those against the adrenocorticotropic cells have distinguished central Cushing's disease patients at risk of incomplete cure after surgical adenoma removal. AHAs to vasopressin cells have identified patients at risk of developing diabetes insipidus. APAs have been also found together with AHAs in patients affected by idiopathic hypopituitarism, but both were also present in different kinds of ...
Frontiers in cellular neuroscience, 2017
From the VGF precursor protein originate several low molecular weight peptides, whose distributio... more From the VGF precursor protein originate several low molecular weight peptides, whose distribution in the brain and blood circulation is not entirely known. Among the VGF peptides, those containing the N-terminus portion were altered in the cerebro-spinal fluid (CSF) and hypothalamus of schizophrenia patients. "Hence, we aimed to better investigate the involvement of the VGF peptides in schizophrenia by studying their localization in the brain regions relevant for the disease, and revealing their possible modulations in response to certain neuronal alterations occurring in schizophrenia". We produced antibodies against different VGF peptides encompassing the N-terminus, but also C-terminus-, TLQP-, GGGE- peptide sequences, and the so named NERP-3 and -4. These antibodies were used to carry out specific ELISA and immunolocalization studies while mass spectrometry (MS) analysis was also performed to recognize the intact brain VGF fragments. We used a schizophrenia rat model,...
PloS one, 2016
VGF mRNA is widely expressed in areas of the nervous system known to degenerate in Amyotrophic La... more VGF mRNA is widely expressed in areas of the nervous system known to degenerate in Amyotrophic Lateral Sclerosis (ALS), including cerebral cortex, brainstem and spinal cord. Despite certain VGF alterations are reported in animal models, little information is available with respect to the ALS patients. We addressed VGF peptide changes in fibroblast cell cultures and in plasma obtained from ALS patients, in parallel with spinal cord and plasma samples from the G93A-SOD1 mouse model. Antisera specific for the C-terminal end of the human and mouse VGF proteins, respectively, were used in immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), while gel chromatography and HPLC/ESI-MS/MS were used to identify the VGF peptides present. Immunoreactive VGF C-terminus peptides were reduced in both fibroblast and plasma samples from ALS patients in an advanced stage of the disease. In the G93A-SOD1 mice, the same VGF peptides were also decreased in plasma in the late-symptomatic st...
Cells, 2022
The authors want to notify that they have made the following changes to the author list of the pa... more The authors want to notify that they have made the following changes to the author list of the paper [...]
Italian journal of anatomy and embryology, 2017
APECED (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Distrophy) is a rare autosomal reces... more APECED (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Distrophy) is a rare autosomal recessive disorder. We previously found that sera samples from 9/14 patients revealed autoantibodies (Auto-Abs) reacting with cerebellum (GABAergic cells, n=5) and substantia nigra (SN; dopaminergic cells, n=5) [1]. Follow-up of the large majority of these patients was perfomed at least 10 years after the previous investigation. Indeed, on these patients, and on control age-matched subjects (n=14), we performed brain examinations using an MRI scanner. Obtained images were used to evaluate the volumes of white and gray matter (W.M and G.M., respectively) as well as the ventricles (III and IV). In addition, we used immunohistochemistry (IHC) on tissues from rat brain (after perfusion with 4% paraformaldehyde) in order to confirm the previous immunoreactivities or found new Auto-Abs cell targets. The brain MR revealed a reduction of G.M (p = 0.042) and cerebellum (p = 0.0012), and an increase of...
Italian journal of anatomy and embryology, 2012
VGF peptides are selectively expressed in neurons and endocrine cells, and were found to be modul... more VGF peptides are selectively expressed in neurons and endocrine cells, and were found to be modulated in the cerebrospinal fluid of patients affected by certain neurodegenerative diseases, as well as decreased in parietal cortex from Parkinson’s disease (PD) patients. We used Sprague-Dowley rats treated with 6-hydroxydopamine (6-OHDA) in the right hemisphere to destroy dopaminergic neurons. Samples of cortex, hypothalamus and substantia nigra (SN) were collected. Human blood samples were obtained from patients affected by PD (n=6) and age-matched controls (n=6, not affected by neurodegenerative disease/s). Specific ELISA were used, as appropriate for rat tissues and human plasma. These were set up with antibodies to: (i) the C- and N-terminal sequences of human / rat VGF precursor, and: (ii) the internal cleaved products: PGH-, TLQP-, and NERP-1 peptides. Preliminary immunohistochemical experiments (IHC) were carried out on control rats, using antibodies to the same VGF-peptides lis...
Development, 1996
During migration and for about 2 days after their arrival in the gonadal ridges, primordial germ ... more During migration and for about 2 days after their arrival in the gonadal ridges, primordial germ cells (the embryonic precursors of gametes of the adult animal) proliferate actively. Certain growth factors, such as stem cell factor and leukemia inhibitory factor, seem to be essential for survival, proliferation and possibly differentiation of mouse primordial germ cell in vivo and/or in vitro. Similarly, increase in intracellular cAMP is followed by a marked enhancement of primordial germ cell proliferation, at least in culture. In the present study, we show that pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP-38), two neuropeptides of the secretin-glucagon-vasoactive intestinal polypeptide-GH-releasing hormone family, stimulate in vitro proliferation of mouse primordial germ cells, bind to primordial germ cells and gonadal somatic cells (possibly to type I PACAP receptor) and activate adenylate cyclase in the same cells. Moreover, PACAP-like immunoreactivity...
Neuropsychopharmacology, 2020
BMJ Open, 2020
IntroductionSevere psychiatric disorders are typically associated with a significant reduction in... more IntroductionSevere psychiatric disorders are typically associated with a significant reduction in life expectancy compared with the general population. Among the different hypotheses formulated to explain this observation, accelerated ageing has been increasingly recognised as the main culprit. At the same time, telomere shortening is becoming widely accepted as a proxy molecular marker of ageing. The present study aims to fill a gap in the literature by better defining the complex interaction/s between inflammation, age-related comorbidities, telomere shortening and gut microbiota in psychiatric disorders.Methods and analysisA cross-sectional study is proposed, recruiting 40 patients for each of three different diagnostic categories (bipolar disorder, schizophrenia and major depressive disorder) treated at the Section of Psychiatry and at the Unit of Clinical Pharmacology of the University Hospital Agency of Cagliari (Italy), compared with 40 age-matched and sex-matched non-psychia...
European Neuropsychopharmacology, 2019
International Journal of Molecular Sciences, 2019
In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential ... more In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential biomarker for dementia with Lewy bodies (DLB). Here, we extended the study of VGF by comparing levels in cerebrospinal fluid (CSF) from 44 DLB patients, 20 Alzheimer’s disease (AD) patients, and 22 cognitively normal controls selected from the Amsterdam Dementia Cohort. CSF was analyzed using two orthogonal analytical methods: (1) In-house-developed quantitative ELISA and (2) selected reaction monitoring (SRM). We further addressed associations of VGF with other CSF biomarkers and cognition. VGF levels were lower in CSF from patients with DLB compared to either AD patients or controls. VGF was positively correlated with CSF tau and α-synuclein (0.55 < r < 0.75), but not with Aβ1-42. In DLB patients, low VGF levels were related to a more advanced cognitive decline at time of first presentation, whereas high levels of VGF were associated with steeper subsequent longitudinal cognitive...
The TLQP-21 peptide peripherally potentiates glucose-stimulated insulin secretion. The aim of thi... more The TLQP-21 peptide peripherally potentiates glucose-stimulated insulin secretion. The aim of this study was to investigate a possible endocrine mechanism through which TLQP-21 increases the insulin secretion. Using an antibody specific for the common N-terminal portion of the TLQP peptides, we studied pancreas and plasma of mice subjected to intraperitoneal glucose load, by immunohistochemistry and immunosorbent assay (ELISA), alone or coupled to High Performance Liquid Chromatography (HLPC). Mice underwent a period of starvation hence have received a glucose load, or saline, and were sacrificed 30 or 120 minutes later. In normal endocrine pancreas, the TLQP-antiserum stained either peripheral or central cells. Interestingly, 30 min after a glucose load, TLQP immunostaining was disappeared in pancreas and, when analysed by ELISA, the TLQP-levels started to increase in plasma reaching peak concentration at 120 min. (controls vs. 30 and 120 min.: p<0.05 and…
International journal of molecular sciences, Jan 3, 2017
This review summarized different studies reporting the presence of autoantibodies reacting agains... more This review summarized different studies reporting the presence of autoantibodies reacting against cells of the pituitary (APAs) and/or hypothalamus (AHAs). Both APAs and AHAs have been revealed through immunofluorescence using different kinds of substrates. Autoantibodies against gonadotropic cells were mainly found in patients affected by cryptorchidism and hypogonadotropic hypogonadism while those against prolactin cells were found in different kinds of patients, the majority without pituitary abnormalities. APAs to growth hormone (GH) cells have been associated with GH deficiency while those against the adrenocorticotropic cells have distinguished central Cushing's disease patients at risk of incomplete cure after surgical adenoma removal. AHAs to vasopressin cells have identified patients at risk of developing diabetes insipidus. APAs have been also found together with AHAs in patients affected by idiopathic hypopituitarism, but both were also present in different kinds of ...
Frontiers in cellular neuroscience, 2017
From the VGF precursor protein originate several low molecular weight peptides, whose distributio... more From the VGF precursor protein originate several low molecular weight peptides, whose distribution in the brain and blood circulation is not entirely known. Among the VGF peptides, those containing the N-terminus portion were altered in the cerebro-spinal fluid (CSF) and hypothalamus of schizophrenia patients. "Hence, we aimed to better investigate the involvement of the VGF peptides in schizophrenia by studying their localization in the brain regions relevant for the disease, and revealing their possible modulations in response to certain neuronal alterations occurring in schizophrenia". We produced antibodies against different VGF peptides encompassing the N-terminus, but also C-terminus-, TLQP-, GGGE- peptide sequences, and the so named NERP-3 and -4. These antibodies were used to carry out specific ELISA and immunolocalization studies while mass spectrometry (MS) analysis was also performed to recognize the intact brain VGF fragments. We used a schizophrenia rat model,...
PloS one, 2016
VGF mRNA is widely expressed in areas of the nervous system known to degenerate in Amyotrophic La... more VGF mRNA is widely expressed in areas of the nervous system known to degenerate in Amyotrophic Lateral Sclerosis (ALS), including cerebral cortex, brainstem and spinal cord. Despite certain VGF alterations are reported in animal models, little information is available with respect to the ALS patients. We addressed VGF peptide changes in fibroblast cell cultures and in plasma obtained from ALS patients, in parallel with spinal cord and plasma samples from the G93A-SOD1 mouse model. Antisera specific for the C-terminal end of the human and mouse VGF proteins, respectively, were used in immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), while gel chromatography and HPLC/ESI-MS/MS were used to identify the VGF peptides present. Immunoreactive VGF C-terminus peptides were reduced in both fibroblast and plasma samples from ALS patients in an advanced stage of the disease. In the G93A-SOD1 mice, the same VGF peptides were also decreased in plasma in the late-symptomatic st...