Neuropeptides and oligopeptidases in schizophrenia

Rodríguez, Benjamín; Nani, João V.; Almeida, Priscila G. C.; Brietzke, Elisa; Lee, Richard S.; Hayashi, Mirian A. F.

doi:10.1016/j.neubiorev.2019.11.024

Cited by 32 publications

(21 citation statements)

References 230 publications

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“…On the other hand, a study evaluating the enzyme activity of another peptidase, namely Angiotensin I-converting enzyme (ACE), which shares common substrates with NDEL1 such as neurotensin (NT), also showed region-specific alterations in the rat brain after chronic treatment with different neuroleptic drugs 39 , 56 . This specificity may be directly related to the neuropeptide system 57 , or it may possibly be a response to the demonstrated increase in neuronal activity in the nucleus accumbens due to chronic treatment with neuroleptics such as haloperidol 58 . Moreover, antipsychotic-induced dopamine supersensitivity, which decreased serotonin 5-HT2A receptor density in the nucleus accumbens (whereas it increased in other brain regions such as the caudate putamen) and enhanced ability of 5-HT2/5-HT2A receptors to modulate dopamine-dependent behaviors, could also be linked to observed changes in 5-HT2A receptor density in the prefrontal cortex and striatum 59 .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics

Nani

Lee

Yonamine

et al. 2020

Sci Rep

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Nuclear distribution element-like 1 (NDEL1) enzyme activity is important for neuritogenesis, neuronal migration, and neurodevelopment. We reported previously lower NDEL1 enzyme activity in blood of treated first episode psychosis and chronic schizophrenia (SCZ) compared to healthy control subjects, with even lower activity in treatment resistant chronic SCZ patients, implicating NDEL1 activity in SCZ. Herein, higher NDEL1 activity was observed in the blood and several brain regions of a validated animal model for SCZ at baseline. In addition, long-term treatment with typical or atypical antipsychotics, under conditions in which SCZ-like phenotypes were reported to be reversed in this animal model for SCZ, showed a significant NDEL1 activity reduction in blood and brain regions which is in line with clinical data. Importantly, these results support measuring NDEL1 enzyme activity in the peripheral blood to predict changes in NDEL1 activity in the CNS. Also, acute administration of psychostimulants, at levels reported to induce SCZ-like phenotype in normal rat strains, increased NDEL1 enzyme activity in blood. Therefore, alterations in NDEL1 activity after treatment with antipsychotics or psychostimulants may suggest a possible modulation of NDEL1 activity secondary to neurotransmission homeostasis and provide new insights into the role of NDEL1 in SCZ pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics

Nani

Lee

Yonamine

et al. 2020

Sci Rep

Self Cite

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“…Such OS is a potential factor in brain deterioration and loss of gray matter, which lead to issues with cognition and daily functioning [ 9 , 10 , 11 , 12 ]; furthermore, OS has been associated with a plethora of psychiatric disorders [ 13 , 14 , 15 , 16 , 17 ]. One such disorder, schizophrenia is characterized by emotional, cognitive, and behavioral disturbances, as well as inaccurate perceptions of reality and high mortality and morbidity [ 18 , 19 , 20 , 21 , 22 ]. Understanding the etiology and pathophysiology of schizophrenia is a prerequisite for developing more effective treatments.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Reactive Oxygen Species-Mediated Damage in the Pathogenesis of Schizophrenia

Madireddy

2020

Brain Sciences

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The biochemical integrity of the brain is paramount to the function of the central nervous system, and oxidative stress is a key contributor to cerebral biochemical impairment. Oxidative stress, which occurs when an imbalance arises between the production of reactive oxygen species (ROS) and the efficacy of the antioxidant defense mechanism, is believed to play a role in the pathophysiology of various brain disorders. One such disorder, schizophrenia, not only causes lifelong disability but also induces severe emotional distress; however, because of its onset in early adolescence or adulthood and its progressive development, consuming natural antioxidant products may help regulate the pathogenesis of schizophrenia. Therefore, elucidating the functions of ROS and dietary antioxidants in the pathogenesis of schizophrenia could help formulate improved therapeutic strategies for its prevention and treatment. This review focuses specifically on the roles of ROS and oxidative damage in the pathophysiology of schizophrenia, as well as the effects of nutrition, antipsychotic use, cognitive therapies, and quality of life on patients with schizophrenia. By improving our understanding of the effects of various nutrients on schizophrenia, it may become possible to develop nutritional strategies and supplements to treat the disorder, alleviate its symptoms, and facilitate long-term recovery.

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“…The most accepted theory to explain the neurobiology of SCZ is based on abnormalities in neurotransmission, as for instance, the alterations in dopaminergic, serotoninergic, glutamatergic, among other signaling pathways [1,4]. The main drugs used to treat SCZ symptoms are antipsychotic drugs, which are usually employed to normalize the dysfunctions in neurotransmission.…”

Section: Introductionmentioning

confidence: 99%

Effects of Psychostimulants and Antipsychotics on Serum Lipids in an Animal Model for Schizophrenia

et al. 2021

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Schizophrenia (SCZ) treatment is essentially limited to the use of typical or atypical antipsychotic drugs, which suppress the main symptoms of this mental disorder. Metabolic syndrome is often reported in patients with SCZ under long-term drug treatment, but little is known about the alteration of lipid metabolism induced by antipsychotic use. In this study, we evaluated the blood serum lipids of a validated animal model for SCZ (Spontaneously Hypertensive Rat, SHR), and a normal control rat strain (Normotensive Wistar Rat, NWR), after long-term treatment (30 days) with typical haloperidol (HAL) or atypical clozapine (CLZ) antipsychotics. Moreover, psychostimulants, amphetamine (AMPH) or lisdexamfetamine (LSDX), were administered to NWR animals aiming to mimic the human first episode of psychosis, and the effects on serum lipids were also evaluated. Discrepancies in lipids between SHR and NWR animals, which included increased total lipids and decreased phospholipids in SHR compared with NWR, were similar to the differences previously reported for SCZ patients relative to healthy controls. Administration of psychostimulants in NWR decreased omega-3, which was also decreased in the first episode of psychosis of SCZ. Moreover, choline glycerophospholipids allowed us to distinguish the effects of CLZ in SHR. Thus, changes in the lipid metabolism in SHR seem to be reversed by the long-term treatment with the atypical antipsychotic CLZ, which was under the same condition described to reverse the SCZ-like endophenotypes of this validated animal model for SCZ. These data open new insights for understanding the potential influence of the treatment with typical or atypical antipsychotics on circulating lipids. This may represent an outcome effect from metabolic pathways that regulate lipids synthesis and breakdown, which may be reflecting a cell lipids dysfunction in SCZ.

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Neuropeptides and oligopeptidases in schizophrenia

Cited by 32 publications

References 230 publications

Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics

Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics

Regulation of Reactive Oxygen Species-Mediated Damage in the Pathogenesis of Schizophrenia

Effects of Psychostimulants and Antipsychotics on Serum Lipids in an Animal Model for Schizophrenia

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