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581 results on '"Mathé, Aleksander A."'

27. Relationship between dopamine D 2 receptor occupancy, clinical response, and drug and monoamine metabolites levels in plasma and cerebrospinal fluid. A pilot study in patients suffering from first-episode schizophrenia treated with quetiapine

Author

Nikisch, Georg, Baumann, Pierre, Kießling, Bernhard, Reinert, Michael, Wiedemann, Georg, Kehr, Jan, Mathé, Aleksander A., Piel, Markus, Roesch, Frank, Weisser, Heike, Schneider, Peter, and Hertel, Andreas

Published
2010
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33. Non-dopaminergic Alterations in Depression-Like FSL Rats in Experimental Parkinsonism and L-DOPA Responses

Author

Schintu, Nicoletta, Zhang, Xiaoqun, Stroth, Nikolas, Mathé, Aleksander A., Andrén, Per E., and Svenningsson, Per

Subjects
Pharmacology, Neurologi, Parkinson's disease, Neurosciences, L-DOPA, tremor, dyskinesia, Neurology, GRASP, flinders sensitive line, Parkinson’s disease, Pharmacology (medical), Neurovetenskaper, Original Research, tamalin
Abstract

Depression is a common comorbid condition in Parkinson's disease (PD). Patients with depression have a two-fold increased risk to develop PD. Further, depression symptoms often precede motor symptoms in PD and are frequent at all stages of the disease. However, the influence of a depressive state on the responses to antiparkinson treatments is largely unknown. In this study, the genetically inbred depression-like flinders sensitive line (FSL) rats and control flinders resistant line (FRL) rats were studied in models of experimental parkinsonism. FSL rats showed a potentiated tremorgenic response to tacrine, a cholinesterase inhibitor used experimentally to induce 6 Hz resting tremor reminiscent of parkinsonian tremor. We also studied rats lesioned with 6-OHDA to induce hemiparkinsonism. No baseline differences in dopaminergic response to acute apomorphine or L-DOPA was found. However, following chronic treatment with L-DOPA, FRL rats developed sensitization of turning and abnormal involuntary movements (AIMs); these effects were counteracted by the anti-dyskinetic 5-HT1A agonist/D-2 partial agonist sarizotan. In contrast, FSL rats did not develop sensitization of turning and only minor AIMs in response to L-DOPA treatment. The roles of several non-dopamine systems underlying this discrepancy were studied. Unexpectedly, no differences of opioid neuropeptides or serotonin markers were found between FRL and FSL rats. The marked behavioral difference between the FRL and FSL rats was paralleled with the striatal expression of the established marker, c-fos, but also the GABAergic transporter (vGAT), and a hitherto unknown marker, tamalin, that is known to regulate mGluR5 receptor function and postsynaptic organization. This study demonstrates that behavioral and transcriptional responses of non-dopaminergic systems to experimental parkinsonism and L-DOPA are modified in a genetic rat model of depression.

Published
2020
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35. Depression-Associated Gene Negr1-Fgfr2 Pathway Is Altered by Antidepressant Treatment

Author

Carboni, L, Pischedda, F, Piccoli, G, Lauria, M, Musazzi, L, Popoli, M, Mathé, A, Domenici, E, Carboni, Lucia, Pischedda, Francesca, Piccoli, Giovanni, Lauria, Mario, Musazzi, Laura, Popoli, Maurizio, Mathé, Aleksander A., Domenici, Enrico, Carboni, L, Pischedda, F, Piccoli, G, Lauria, M, Musazzi, L, Popoli, M, Mathé, A, Domenici, E, Carboni, Lucia, Pischedda, Francesca, Piccoli, Giovanni, Lauria, Mario, Musazzi, Laura, Popoli, Maurizio, Mathé, Aleksander A., and Domenici, Enrico

Abstract

The Negr1 gene has been significantly associated with major depression in genetic studies. Negr1 encodes for a cell adhesion molecule cleaved by the protease Adam10, thus activating Fgfr2 and promoting neuronal spine plasticity. We investigated whether antidepressants modulate the expression of genes belonging to Negr1-Fgfr2 pathway in Flinders sensitive line (FSL) rats, in a corticosterone-treated mouse model of depression, and in mouse primary neurons. Negr1 and Adam10 were the genes mostly affected by antidepressant treatment, and in opposite directions. Negr1 was down-regulated by escitalopram in the hypothalamus of FSL rats, by fluoxetine in the hippocampal dentate gyrus of corticosterone-treated mice, and by nortriptyline in hippocampal primary neurons. Adam10 mRNA was increased by nortriptyline administration in the hypothalamus, by escitalopram in the hippocampus of FSL rats, and by fluoxetine in mouse dorsal dentate gyrus. Similarly, nortriptyline increased Adam10 expression in hippocampal cultures. Fgfr2 expression was increased by nortriptyline in the hypothalamus of FSL rats and in hippocampal neurons. Lsamp, another IgLON family protein, increased in mouse dentate gyrus after fluoxetine treatment. These findings suggest that Negr1-Fgfr2 pathway plays a role in the modulation of synaptic plasticity induced by antidepressant treatment to promote therapeutic efficacy by rearranging connectivity in corticolimbic circuits impaired in depression.

Published
2020

36. Gene expression signature of antidepressant treatment response/non-response in Flinders Sensitive Line rats subjected to maternal separation

Author

Marchetti, L, Lauria, M, Caberlotto, L, Musazzi, L, Popoli, M, Mathé, A, Domenici, E, Carboni, L, Marchetti, Luca, Lauria, Mario, Caberlotto, Laura, Musazzi, Laura, Popoli, Maurizio, Mathé, Aleksander A, Domenici, Enrico, Carboni, Lucia, Marchetti, L, Lauria, M, Caberlotto, L, Musazzi, L, Popoli, M, Mathé, A, Domenici, E, Carboni, L, Marchetti, Luca, Lauria, Mario, Caberlotto, Laura, Musazzi, Laura, Popoli, Maurizio, Mathé, Aleksander A, Domenici, Enrico, and Carboni, Lucia

Abstract

Neurobiological underpinnings of treatment-resistant depression, a debilitating condition associated with significant functional impairment, have not been elucidated. Consequently, the aim of this study was to use animal models of response and resistance to antidepressant treatment, in an attempt to identify differences in associated transcriptional responses. Flinders Sensitive Line rats were subjected to maternal separation (MS) and chronically treated with Escitalopram or Nortriptyline. Antidepressants reduced immobility time in the forced swim test in non-MS rats, while lack of antidepressant behavioural response was observed in MS animals. We developed a novel bioinformatic algorithm that enabled identification of transcriptional signatures in hippocampus and pre-frontal cortex that discriminate vehicle- and antidepressant-treated subjects in both MS and non-MS rats. Functional annotation analysis showed that in antidepressant-responder rats the most enriched pathways included IQGAPs activation, toll-like receptor trafficking, energy metabolism, and regulation of endopeptidase activity. The analysis of interacting proteins implicated synaptic vesicles and neurotransmitter release, ubiquitin regulation, cytoskeleton organisation and carbohydrate metabolism. In contrast, in treatment-resistant MS rats, main expression changes were revealed in ribosomal proteins, inflammatory responses, transcriptional/epigenetic regulation, and small GTPases. Susceptibility signature shared Rtn1, Zdhhc5, Igsf6, and Sim1 genes with the latest depression GWAS meta-analysis, while antidepressant resistance signature shared Ctnnd1, Rbms3, Atp1a3, and Pla2r1 genes. In conclusion, this study demonstrated that distinct transcriptional signatures are associated with behavioural response or non-response to antidepressant treatment. The identification of genes involved in antidepressant response will increase the comprehension of the neurobiological underpinnings of treatment-resistant dep

Published
2020

43. Sirtuins and neuropeptide y downregulation in Flinders Sensitive Line rat model of depression.

Author

Stiernborg, Miranda, Efstathopoulos, Paschalis, Lennartsson, Andreas, Lavebratt, Catharina, and Mathé, Aleksander A.

Subjects
NEUROPEPTIDE Y, SIRTUINS, ANIMAL disease models, DEACETYLASES, PREFRONTAL cortex
Abstract

Since the NAD+-dependent histone deacetylases sirtuin-1 (SIRT1) and sirtuin-2 (SIRT2) are critically involved in epigenetics, endocrinology and immunology and affect the longevity in model organisms, we investigated their expression in brains of 3-month-old and 14–15 months old rat model of depression Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats. In view of the dysregulated NPY system in depression, we also studied NPY in young and old FSL to explore the temporal trajectory of depressive-like–ageing interaction. Sirt1, Sirt2 and Npy mRNA were determined using qRT-PCR in prefrontal cortex (PFC) from young and old FSL and FRL, and in hippocampi from young FSL and FRL. PFC: Sirt1 expression was decreased in FSL (p = 0.001). An interaction between age and genotype was found (p = 0.032); young FSL had lower Sirt1 with respect to both age (p = 0.026) and genotype (p = 0.001). Sirt2 was lower in FSL (p = 0.003). Npy mRNA was downregulated in FSL (p = 0.001) but did not differ between the young and old rat groups. Hippocampus: Sirt1 was reduced in young FSL compared to young FRL (p = 0.005). There was no difference in Sirt2 between FSL and FRL. Npy levels were decreased in hippocampus of young FSL compared to young FRL (p = 0.003). Effects of ageing could not be investigated due to loss of samples. To conclude, i this is the first demonstration that SIRT1 and SIRT2 are changed in brain of FSL, a rat model of depression; ii the changes are age-dependent; iii sirtuins are potential targets for treatment of age-related neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Published
2022
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47. Synaptoproteomics of Existing and new Animal Models of Depression

Author

Mallei, Alessandra, primary, Giambelli, Roberto, additional, Khoury, Aram El, additional, Gruber, Susanne H. M., additional, Musazzi, Laura, additional, Barbiero, Valentina S., additional, Tardito, Daniela, additional, Vollmayr, Barbara, additional, Gass, Peter, additional, Mathé, Aleksander A., additional, Racagni, Giorgio, additional, and Popoli, Maurizio, additional

Published
2008
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