Proceedings of the 32nd National Conference of the Italian Group for the Study of Neuromorphology... more Proceedings of the 32nd National Conference of the Italian Group for the Study of Neuromorphology “Gruppo Italiano per lo Studio della Neuromorfologia” G.I.S.N., Naples, November 25-26, 2022
Age-related macular degeneration is an incurable chronic neurodegenerative disease, which causes ... more Age-related macular degeneration is an incurable chronic neurodegenerative disease, which causes progressive loss of the central vision and even blindness. All current treatments aim at slowing down the progression of the disease. In the present paper we provide in vitro evidence for the feasibility of layered biohybrid retinas built with silk silkworm fibroin and cultures of different types of cells: retinal pigment epithelium, retinal neurons, Müller and mesenchymal stem cells. The layers of the biohybrid retina are glued together with silk fibroin hydrogel. In vitro tests show primary culture neurons grow and develop neurites on silk fibroin biofilms alone, or in presence of other cells cultivated on the same biomaterial, the organization of the cells and the cellular phenotypes, are maintained during the 7 days of the experiment.
Remodeling of neural networks in the anterior forebrain of an animal model of hyperactivity and a... more Remodeling of neural networks in the anterior forebrain of an animal model of hyperactivity and attention deficits as monitored by molecular imaging probes. These studies report on the remodeling of neural networks which are likely to be the consequences of the segmental defect in the anterior forebrain of an animal model of hyperactivity and attention-deficit, the juvenile prehypertensive male spontaneously hypertensive rat (SHR). Molecular biology and microscope imaging techniques were used such as: (i) dopamine (DA) D-1 and D-2 receptors by radioligand binding studies; (ii) the Ca2+/Calmodulin-dependent protein kinase II (CaMKII); (iii) transcription factors (TF) such as c-FOS by Immunocytochemistry; and (iv) the respiratory chain enzyme cytochrome-oxidase (C.O.), as markers of neuronal activity in the anterior forebrain of SHR and Wistar Kyoto normotensive (WKY) controls rats. Microcomputer-assisted high-resolution image analysis using DA receptor binding and C.O., as probes revealed by cross-correlations among different regions within brain an altered cross-talk in the anterior forebrain of the SHR as compared to the controls. In particular, an altered cross-talk was also observed within the amygdala complex in the SHR by CaMKII and c-FOS expression. Therefore, the hypothesized segmental defect in the anterior forebrain of the SHR produces network consequences leading to behavioral alteration in the attentional activity and emotional domains. Subchronic treatment with metilphenidate (MP) that is known to block the reuptake of biogenic amines (mainly DA) produced network remodeling which are known to be paralleled by behavioral modifications in the attentive activity and emotional domains. Imperspective, the results from this model system that features the main aspects of attention-deficit hyperactivity disorder (ADHD), can be useful for the understanding of the neural substrates of hyperactivity and attention deficits and possibly for an early diagnosis and appropriate treatment of ADHD children.
Annals of the New York Academy of Sciences, Dec 17, 2006
The role of nitric oxide in learning and memory processes has been tested in the albino rat by a ... more The role of nitric oxide in learning and memory processes has been tested in the albino rat by a histochemical and a behavioral study, following behavioral habituation to spatial novelty. Histochemically, the neural consequences of behavioral testing were mapped in the brain by staining for NADPH-d, known to be a NOS, whereas behaviorally the formation of LTH has been interfered with by posttrial NOS-inhibition. In the histochemical study, adult male Sprague-Dawley rats were tested in a Làt-maze and sacrificed at different time intervals thereafter. Handled unexposed rats served as controls. The brains were perfused with aldheide and processed for NADPH-d staining. In unexposed control rats the basal expression of NADPH-d was low and scattered. It pertained to few cells in the neostriatum, cerebral cortex, and CA1 hippocampal regions. In contrast, rats that had been exposed for the first time to the maze (spatial novelty) showed NADPH-d activity in the dorsal hippocampus (granule cells, few hilar neurons, and some CA1 pyramidal cells), the caudate-putamen complex, the cerebellum, and in all layers of somatosensory cortex. The positivity was not due to activity per se, since immediately after exposure it was not different from baseline. In contrast, it was present by 2 h and decreased significantly 24 h later. In addition, a strong neuronal discharge induced by the convulsant pentylentetrazol did not induce NADPH-d 2 h afterwards. The staining was prevented by pretreatment with the NMDA receptor antagonist CPP (5 mg/kg) or with the NOS inhibitor L-NOARG (10 mg/kg). In the behavioral study, rats were given an intraperitoneal injection of 1-10 mg/kg (L-NOARG) or vehicle immediately following exposure to a Làt-maze. The highest dose used (10 mg/kg) disrupted habituation of the vertical component only, known to be mainly of emotional meaning. Conversely, both doses disrupted emotional habituation based on defecation scores. The data indicate that the formation of LTH to novelty triggers a cascade of neurochemical events also involving NOS neurons. Further, the widespread induction of NADPH-d by exposure to novelty suggests that spatial and emotional information processing activate neural networks across different organizational levels of the CNS.
In the central nervous system (CNS), the Na(+)-Ca(2+) exchanger plays a fundamental role in contr... more In the central nervous system (CNS), the Na(+)-Ca(2+) exchanger plays a fundamental role in controlling the changes in the intracellular concentrations of Na(+) and Ca(2+) ions. These cations are known to regulate neurotransmitter release, cell migration and differentiation, gene expression, and neurodegenerative processes. In the present study, nonradioactive in situ hybridization and light immunohistochemistry were carried out to map the regional and cellular distribution for both transcripts and proteins encoded by the three known Na(+)-Ca(2+) exchanger genes NCX1, NCX2, and NCX3. NCX1 transcripts were particularly expressed in layers III-V of the motor cortex, in the thalamus, in CA3 and the dentate gyrus of the hippocampus, in several hypothalamic nuclei, and in the cerebellum. NCX2 transcripts were strongly expressed in all hippocampal subregions, in the striatum, and in the paraventricular thalamic nucleus. NCX3 mRNAs were mainly detected in the hippocampus, in the thalamus, in the amygdala, and in the cerebellum. Immunohistochemical analysis revealed that NCX1 protein was mainly expressed in the supragranular layers of the cerebral cortex, in the hippocampus, in the hypothalamus, in the substantia nigra and ventral tegmental area, and in the granular layer of the cerebellum. The NCX2 protein was predominantly expressed in the hippocampus, in the striatum, in the thalamus, and in the hypothalamus. The NCX3 protein was particularly found in the CA3 subregion, and in the oriens, radiatum, and lacunoso-moleculare layers of the hippocampus, in the ventral striatum, and in the cerebellar molecular layer. Collectively, these results suggest that the different Na(+)-Ca(2+) exchanger isoforms appear to be selectively expressed in several CNS regions where they might underlie different functional roles.
Progress in Molecular Biology and Translational Science, 2017
The functionality and stability of the central nervous system (CNS) pabulum, called neural extrac... more The functionality and stability of the central nervous system (CNS) pabulum, called neural extracellular matrix (nECM), is paramount for the maintenance of a healthy network. The loosening or the damage of the scaffold disrupts synaptic transmission with the consequent imbalance of the neurotransmitters, reactive cells invasion, astrocytosis, new matrix deposition, digestion of the previous structure and ultimately, maladaptive plasticity with the loss of neuronal viability. nECM is constantly affected by CNS disorders, particularly in chronic modifying such as neurodegenerative disease, or in acute/subacute with chronic sequelae, like cerebrovascular and inflammatory pathology. Matrix metalloproteinases (MMPs) are the main interfering agent of nECM, guiding the balance of degradation and new deposition of proteins such as proteoglycans and glycoproteins, or glycosaminoglycans, such as hyaluronic acid. Activation of these enzymes is modulated by their physiologic inhibitors, the tissue inhibitors of MMPs or via other proteases inhibitors, as well as genetic or epigenetic up- or downregulation through molecular interaction or receptor activation. The appropriate understanding of the pathways underlying nECM modifications in CNS pathology is probably one of the pivotal future directions to identify the healthy brain network and subsequently design new therapies to interfere with the progression of the CNS disease and eventually find appropriate therapies.
Nell’uomo, la maggior parte della superficie mediale degli emisferi cerebrali è occupata dalla ne... more Nell’uomo, la maggior parte della superficie mediale degli emisferi cerebrali è occupata dalla neocortex notevolmente espansa. Comunque, su questo lato dell’encefalo, sono presenti anche numerose strutture che non sono neocorticali. Due di queste, il sistema olfattorio centrale e il setto, occupano una posizione superficiale, mentre altre due, il complesso amigdaloideo e la formazione ippocampale, sono per la maggior parte nascoste
Herrick [9, 10] ha diviso il diencefalo in quattro zone longitudinali: l’epitalamo, il talamo dor... more Herrick [9, 10] ha diviso il diencefalo in quattro zone longitudinali: l’epitalamo, il talamo dorsale, il talamo ventrale e l’ipotalamo. Questa suddivisione è stata ampiamente condivisa dalla comunità scientifica ed è stato asserito che poteva essere applicata a tutte le classi di vertebrati, inclusi i mammiferi [3, 27] e l’uomo [5, 11, 12, 26]. Sebbene attualmente sia noto (vedi Cap.
Proceedings of the 32nd National Conference of the Italian Group for the Study of Neuromorphology... more Proceedings of the 32nd National Conference of the Italian Group for the Study of Neuromorphology “Gruppo Italiano per lo Studio della Neuromorfologia” G.I.S.N., Naples, November 25-26, 2022
Age-related macular degeneration is an incurable chronic neurodegenerative disease, which causes ... more Age-related macular degeneration is an incurable chronic neurodegenerative disease, which causes progressive loss of the central vision and even blindness. All current treatments aim at slowing down the progression of the disease. In the present paper we provide in vitro evidence for the feasibility of layered biohybrid retinas built with silk silkworm fibroin and cultures of different types of cells: retinal pigment epithelium, retinal neurons, Müller and mesenchymal stem cells. The layers of the biohybrid retina are glued together with silk fibroin hydrogel. In vitro tests show primary culture neurons grow and develop neurites on silk fibroin biofilms alone, or in presence of other cells cultivated on the same biomaterial, the organization of the cells and the cellular phenotypes, are maintained during the 7 days of the experiment.
Remodeling of neural networks in the anterior forebrain of an animal model of hyperactivity and a... more Remodeling of neural networks in the anterior forebrain of an animal model of hyperactivity and attention deficits as monitored by molecular imaging probes. These studies report on the remodeling of neural networks which are likely to be the consequences of the segmental defect in the anterior forebrain of an animal model of hyperactivity and attention-deficit, the juvenile prehypertensive male spontaneously hypertensive rat (SHR). Molecular biology and microscope imaging techniques were used such as: (i) dopamine (DA) D-1 and D-2 receptors by radioligand binding studies; (ii) the Ca2+/Calmodulin-dependent protein kinase II (CaMKII); (iii) transcription factors (TF) such as c-FOS by Immunocytochemistry; and (iv) the respiratory chain enzyme cytochrome-oxidase (C.O.), as markers of neuronal activity in the anterior forebrain of SHR and Wistar Kyoto normotensive (WKY) controls rats. Microcomputer-assisted high-resolution image analysis using DA receptor binding and C.O., as probes revealed by cross-correlations among different regions within brain an altered cross-talk in the anterior forebrain of the SHR as compared to the controls. In particular, an altered cross-talk was also observed within the amygdala complex in the SHR by CaMKII and c-FOS expression. Therefore, the hypothesized segmental defect in the anterior forebrain of the SHR produces network consequences leading to behavioral alteration in the attentional activity and emotional domains. Subchronic treatment with metilphenidate (MP) that is known to block the reuptake of biogenic amines (mainly DA) produced network remodeling which are known to be paralleled by behavioral modifications in the attentive activity and emotional domains. Imperspective, the results from this model system that features the main aspects of attention-deficit hyperactivity disorder (ADHD), can be useful for the understanding of the neural substrates of hyperactivity and attention deficits and possibly for an early diagnosis and appropriate treatment of ADHD children.
Annals of the New York Academy of Sciences, Dec 17, 2006
The role of nitric oxide in learning and memory processes has been tested in the albino rat by a ... more The role of nitric oxide in learning and memory processes has been tested in the albino rat by a histochemical and a behavioral study, following behavioral habituation to spatial novelty. Histochemically, the neural consequences of behavioral testing were mapped in the brain by staining for NADPH-d, known to be a NOS, whereas behaviorally the formation of LTH has been interfered with by posttrial NOS-inhibition. In the histochemical study, adult male Sprague-Dawley rats were tested in a Làt-maze and sacrificed at different time intervals thereafter. Handled unexposed rats served as controls. The brains were perfused with aldheide and processed for NADPH-d staining. In unexposed control rats the basal expression of NADPH-d was low and scattered. It pertained to few cells in the neostriatum, cerebral cortex, and CA1 hippocampal regions. In contrast, rats that had been exposed for the first time to the maze (spatial novelty) showed NADPH-d activity in the dorsal hippocampus (granule cells, few hilar neurons, and some CA1 pyramidal cells), the caudate-putamen complex, the cerebellum, and in all layers of somatosensory cortex. The positivity was not due to activity per se, since immediately after exposure it was not different from baseline. In contrast, it was present by 2 h and decreased significantly 24 h later. In addition, a strong neuronal discharge induced by the convulsant pentylentetrazol did not induce NADPH-d 2 h afterwards. The staining was prevented by pretreatment with the NMDA receptor antagonist CPP (5 mg/kg) or with the NOS inhibitor L-NOARG (10 mg/kg). In the behavioral study, rats were given an intraperitoneal injection of 1-10 mg/kg (L-NOARG) or vehicle immediately following exposure to a Làt-maze. The highest dose used (10 mg/kg) disrupted habituation of the vertical component only, known to be mainly of emotional meaning. Conversely, both doses disrupted emotional habituation based on defecation scores. The data indicate that the formation of LTH to novelty triggers a cascade of neurochemical events also involving NOS neurons. Further, the widespread induction of NADPH-d by exposure to novelty suggests that spatial and emotional information processing activate neural networks across different organizational levels of the CNS.
In the central nervous system (CNS), the Na(+)-Ca(2+) exchanger plays a fundamental role in contr... more In the central nervous system (CNS), the Na(+)-Ca(2+) exchanger plays a fundamental role in controlling the changes in the intracellular concentrations of Na(+) and Ca(2+) ions. These cations are known to regulate neurotransmitter release, cell migration and differentiation, gene expression, and neurodegenerative processes. In the present study, nonradioactive in situ hybridization and light immunohistochemistry were carried out to map the regional and cellular distribution for both transcripts and proteins encoded by the three known Na(+)-Ca(2+) exchanger genes NCX1, NCX2, and NCX3. NCX1 transcripts were particularly expressed in layers III-V of the motor cortex, in the thalamus, in CA3 and the dentate gyrus of the hippocampus, in several hypothalamic nuclei, and in the cerebellum. NCX2 transcripts were strongly expressed in all hippocampal subregions, in the striatum, and in the paraventricular thalamic nucleus. NCX3 mRNAs were mainly detected in the hippocampus, in the thalamus, in the amygdala, and in the cerebellum. Immunohistochemical analysis revealed that NCX1 protein was mainly expressed in the supragranular layers of the cerebral cortex, in the hippocampus, in the hypothalamus, in the substantia nigra and ventral tegmental area, and in the granular layer of the cerebellum. The NCX2 protein was predominantly expressed in the hippocampus, in the striatum, in the thalamus, and in the hypothalamus. The NCX3 protein was particularly found in the CA3 subregion, and in the oriens, radiatum, and lacunoso-moleculare layers of the hippocampus, in the ventral striatum, and in the cerebellar molecular layer. Collectively, these results suggest that the different Na(+)-Ca(2+) exchanger isoforms appear to be selectively expressed in several CNS regions where they might underlie different functional roles.
Progress in Molecular Biology and Translational Science, 2017
The functionality and stability of the central nervous system (CNS) pabulum, called neural extrac... more The functionality and stability of the central nervous system (CNS) pabulum, called neural extracellular matrix (nECM), is paramount for the maintenance of a healthy network. The loosening or the damage of the scaffold disrupts synaptic transmission with the consequent imbalance of the neurotransmitters, reactive cells invasion, astrocytosis, new matrix deposition, digestion of the previous structure and ultimately, maladaptive plasticity with the loss of neuronal viability. nECM is constantly affected by CNS disorders, particularly in chronic modifying such as neurodegenerative disease, or in acute/subacute with chronic sequelae, like cerebrovascular and inflammatory pathology. Matrix metalloproteinases (MMPs) are the main interfering agent of nECM, guiding the balance of degradation and new deposition of proteins such as proteoglycans and glycoproteins, or glycosaminoglycans, such as hyaluronic acid. Activation of these enzymes is modulated by their physiologic inhibitors, the tissue inhibitors of MMPs or via other proteases inhibitors, as well as genetic or epigenetic up- or downregulation through molecular interaction or receptor activation. The appropriate understanding of the pathways underlying nECM modifications in CNS pathology is probably one of the pivotal future directions to identify the healthy brain network and subsequently design new therapies to interfere with the progression of the CNS disease and eventually find appropriate therapies.
Nell’uomo, la maggior parte della superficie mediale degli emisferi cerebrali è occupata dalla ne... more Nell’uomo, la maggior parte della superficie mediale degli emisferi cerebrali è occupata dalla neocortex notevolmente espansa. Comunque, su questo lato dell’encefalo, sono presenti anche numerose strutture che non sono neocorticali. Due di queste, il sistema olfattorio centrale e il setto, occupano una posizione superficiale, mentre altre due, il complesso amigdaloideo e la formazione ippocampale, sono per la maggior parte nascoste
Herrick [9, 10] ha diviso il diencefalo in quattro zone longitudinali: l’epitalamo, il talamo dor... more Herrick [9, 10] ha diviso il diencefalo in quattro zone longitudinali: l’epitalamo, il talamo dorsale, il talamo ventrale e l’ipotalamo. Questa suddivisione è stata ampiamente condivisa dalla comunità scientifica ed è stato asserito che poteva essere applicata a tutte le classi di vertebrati, inclusi i mammiferi [3, 27] e l’uomo [5, 11, 12, 26]. Sebbene attualmente sia noto (vedi Cap.
Uploads
Papers by Michele Papa