Neudesin is involved in anxiety behavior: structural and neurochemical correlates

Novais, Ashley Cruz; Ferreira, Ana Catarina; Marques, Fernanda; Pêgo, José M.; Cerqueira, João José; David-Pereira, Ana; Campos, Filipa; Dalla, Christina; Kokras, Nikolaos; Sousa, Nuno; Palha, Joana Almeida; Sousa, João Carlos

doi:10.3389/fnbeh.2013.00119

Cited by 27 publications

(24 citation statements)

References 46 publications

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“…Turnover rates of 5-HT and DA (5-HIAA/5-HT as well as HVA/DA and DOPAC/DA, respectively) were calculated as indices of serotonergic and dopaminergic activity, respectively. Monoamine turnover rates are more reliable indices of neurotransmission activity than absolute levels of monoamine, as they integrate synthesis, release, reuptake, and metabolism of neurotransmitters in the synapse (56 (95% O 2 , 5% CO 2 )]. Both extracellular recordings [Multiclamp 700B amplifier (Axon Instruments) and borosilicate glass pipettes with saline (3-5 MΩ)] and stimulation (bipolar tungsten electrode) were performed in the middle of the stratum radiatum of CA1.…”

Section: Methodsmentioning

confidence: 99%

“…Reverse-phase ion pairing chromatography was used to assay monoamines and their metabolites using an Aquasil C18HPLC column (250 × 4.6 mm, 5 μm; ThermoElectron). Samples were quantified by comparison of the area under the curve against known external reference standards using a PC-compatible HPLC software package (Chromatography Station) as previously described (56). The limit of detection was 1 pg/20 μL (injection volume).…”

Section: Methodsmentioning

confidence: 99%

“…Dorsal hippocampi were homogenized and deproteinized (0.1 N perchloric acid solution, 7.9 mM Na 2 S 2 O 5 , 1.3 mM Na 2 EDTA). After centrifugation (20,000 × g, 45 min), supernatant was analyzed using a GBC LC 1150 HPLC pump (GBC Scientific Equipment) coupled with a BAS-LC4C (Bioanalytical Systems Inc.) electrochemical detector (+800 mV), as previously described (56). Reverse-phase ion pairing chromatography was used to assay monoamines and their metabolites using an Aquasil C18HPLC column (250 × 4.6 mm, 5 μm; ThermoElectron).…”

Section: Methodsmentioning

confidence: 99%

“…Trials were captured on a video-tracking system (Viewpoint). The distance that animals swam to reach the hidden platform was recorded and used to evaluate learning and memory performances (11,56). NOR.…”

Section: Methodsmentioning

confidence: 99%

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Tau protein is essential for stress-induced brain pathology

Lopes

Vaz‐Silva

Pinto

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Exposure to chronic stress is frequently accompanied by cognitive and affective disorders in association with neurostructural adaptations. Chronic stress was previously shown to trigger Alzheimer's-like neuropathology, which is characterized by Tau hyperphosphorylation and missorting into dendritic spines followed by memory deficits. Here, we demonstrate that stress-driven hippocampal deficits in wild-type mice are accompanied by synaptic missorting of Tau and enhanced Fyn/GluN2B-driven synaptic signaling. In contrast, mice lacking Tau [Tau knockout (Tau-KO) mice] do not exhibit stress-induced pathological behaviors and atrophy of hippocampal dendrites or deficits of hippocampal connectivity. These findings implicate Tau as an essential mediator of the adverse effects of stress on brain structure and function.Tau | stress | hippocampus | depression | memory deficits T he cytoskeletal protein Tau is implicated in the establishment of Alzheimer's disease (AD) (1) as well as excitotoxicity (1) and, more recently, epilepsy (2, 3). Exposure to stressful conditions induces depressive behavior and memory deficits in both rodents and humans (4-8). Studies in rodents have shown that chronic stress triggers Tau hyperphosphorylation, a key pathogenic mechanism in AD, and results in cognitive and mood deficits (9-13); however, those studies do not provide direct evidence for a role of Tau in stress-evoked brain pathology. Given that Tau plays an important role in regulating neuronal architecture and function through its interaction with various cellular targets (e.g., tubulin and Fyn) (14), we hypothesized that Tau mediates the deleterious actions of stress on brain structure and function.To test the above hypothesis, we compared the impact of chronic unpredictable stress (CUS) (11, 15) in mice carrying a null mutation of the mapt gene [Tau knockout (Tau-KO) mice] (16) with their wild-type (WT) littermates. Three well-characterized behavioral endpoints (cognition, coping styles, and anxiety) that are disrupted by CUS served as the primary assay endpoints; these were complemented with measures of hippocampal structural and functional integrity. The hippocampus is a central component of the neurocircuitries that control these behaviors and displays overt lesions in both stress-and Tau-related pathologies; in the latter, the hippocampus is one of the earliest brain regions to show signs of neurodegeneration (1,4,7,(10)(11)(12)(13)17). ResultsDeleterious Effects of Stress on Memory and Mood Are Abrogated in the Absence of Tau Protein. Cognition, mood, and anxiety are interdependent behavioral domains that exhibit complex interactions (5). Different forms of memory were assessed after exposure of WT and Tau-KO mice to the CUS paradigm; the test battery included the Y-maze, Morris water maze (MWM), and the novel object recognition test (NOR). Anxiety was evaluated using the elevated plus maze (EPM), and coping styles and anhedonia were assessed using the forced swim test (FST) and the sucrose consumption test (SCT).Two-way ANOVA ...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Tau protein is essential for stress-induced brain pathology

Lopes

Vaz‐Silva

Pinto

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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125

111

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“…Byerly et al reported that the administration of recombinant neudesin to the hypothalamus repressed appetite. Novais et al generated neudesin knockout (KO) mice and reported that deletion of the neudesin gene resulted in increased anxious-like behavior caused by insufficient development of hippocampal neurons 21) . These results showed that neudesin is crucial for neuronal development and function.…”

Section: Introductionmentioning

confidence: 99%

Role of the secretory protein neudesin in energy metabolism

Ohta

2016

JPFSM

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The epidemic of obesity has become a serious health challenge in both developed and developing countries. Since the identification of leptin, a secretory protein from the white adipose tissue, secretory proteins have become recognized as important regulators of energy metabolism. We previously identified neudesin as a novel secretory protein. We also showed that neudesin was strongly expressed in central the nervous system of embryonic and adult mice, and was expressed in various peripheral tissues of adult mice. Thus, in this review, we discuss the physiological roles of neudesin and focus on its involvement in energy metabolism. We generated neudesin knockout (KO) mice, and showed that they were resistant to highfat diet (HFD)-induced obesity. Neudesin KO mice were protected from HFD-induced insulin resistance and hepatic steatosis. Furthermore, neudesin KO mice showed increased energy expenditure due to enhanced sympathetic nervous activity (SNA). Thus, resistance to HFDinduced obesity in neudesin KO mice was the result of increased energy expenditure. Neudesin KO mice also showed increased heat production and fatty acid oxidation in the adipose tissue. These results suggest that neudesin might act on neurons and adipocytes to suppress SNA. In conclusion, we establish the role of neudesin as a supressor of energy expenditure via regulating SNA. Neudesin is a novel regulator of energy metabolism and might be a target for the treatment of obesity and obesity-related metabolic syndrome.

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Neurochemical Effects of Long Term Consumption of High Fat Diet

Farooqui¹

2015

High Calorie Diet and the Human Brain

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Neudesin is involved in anxiety behavior: structural and neurochemical correlates

Cited by 27 publications

References 46 publications

Tau protein is essential for stress-induced brain pathology

Tau protein is essential for stress-induced brain pathology

Role of the secretory protein neudesin in energy metabolism

Neurochemical Effects of Long Term Consumption of High Fat Diet

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