Effect of transient blockade of <i>N</i>‐methyl‐<scp>D</scp>‐aspartate receptors at neonatal stage on stress‐induced lactate metabolism in the medial prefrontal cortex of adult rats: Role of 5‐HT1A receptor agonism

Uehara, Takashi; Itoh, Hiroko; Matsuoka, Tadasu; Rujescu, Dan; Genius, Just; T, Seo; Sumiyoshi, Tomiki

doi:10.1002/syn.21529

Cited by 13 publications

(19 citation statements)

References 77 publications

(107 reference statements)

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“…A correct balance between glucose (low level) and lactate (high level) reveals a correct energy metabolism of neurons. On the contrary, an insufficient lactate production indicates poor metabolic neuronal function and reduced protection against insult (Uehara et al, 2012;Wyss et al, 2011;Newman et al, 2011).…”

Section: Glucose and Lactate Levels In Str Hip And Mpfcmentioning

confidence: 99%

Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

et al. 2013

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a b s t r a c tPesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases. Previous studies investigated the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present study was designed to characterize the cognitive deficits in the current animal model. When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls. No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task. Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus. The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls. The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h after the last treatment was 41.50 g/L and it was completely eliminated after 96 h.

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Section: Glucose and Lactate Levels In Str Hip And Mpfcmentioning

confidence: 99%

Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

et al. 2013

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“…did not suppress FS-induced eLAC elevation in the mPFC of saline-treated rats, in contrast to our previous observation with tandospirone at 2.0 mg/kg (Uehara et al, 2006). Moreover, the drug at 0.1, 1.0, or 5.0 mg/kg attenuated FS-induced eLAC increment (Uehara et al, 2012a), although last injection was 24 h before eLAC measurement.…”

Section: Discussionmentioning

confidence: 99%

“…We previously reported that the long-term effect of transient MK-801 treatment in neonatal periods on lactate metabolism in the mPFC of young adult rats (Uehara et al, 2012a). According to the study, transient MK-801 treatment in neonatal stage suppressed FS stress-induced eLAC elevation in the mPFC without changes in the basal levels.…”

Section: Discussionmentioning

confidence: 99%

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Tandospirone, a 5-HT1A partial agonist, ameliorates aberrant lactate production in the prefrontal cortex of rats exposed to blockade of N-methy-D-aspartate receptors; Toward the therapeutics of cognitive impairment of schizophrenia

Uehara

Matsuoka²,

Sumiyoshi

2014

Front. Behav. Neurosci.

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Rationale: Augmentation therapy with serotonin-1A (5-HT1A) receptor partial agonists has been suggested to improve cognitive impairment in patients with schizophrenia. Decreased activity of prefrontal cortex may provide a basis for cognitive deficits of the disease. Lactate plays a significant role in the supply of energy to the brain, and glutamatergic neurotransmission contributes to lactate production.Objectives and methods: The purposes of this study were to examine the effect of repeated administration (once a daily for 4 days) of tandospirone (0.05 or 5 mg/kg) on brain energy metabolism, as represented by extracellular lactate concentration (eLAC) in the medial prefrontal cortex (mPFC) of a rat model of schizophrenia.Results: Four-day treatment with MK-801, an NMDA-R antagonist, prolonged eLAC elevation induced by foot-shock stress (FS). Co-administration with the high-dose tandospirone suppressed prolonged FS-induced eLAC elevation in rats receiving MK-801, whereas tandospirone by itself did not affected eLAC increment.Conclusions: These results suggest that stimulation of 5-HT1A receptors ameliorates abnormalities of energy metabolism in the mPFC due to blockade of NMDA receptors. These findings provide a possible mechanism, based on brain energy metabolism, by which 5-HT1A agonism improve cognitive impairment of schizophrenia and related disorders.

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“…Lactate metabolism was hypothesized to reflect energy supply in the brain areas crucial for cognitive functions, e.g., PFC. Figure 8 describes the effect of tandospirone on extracellular lactate concentrations in a rat model of schizophrenia (Uehara et al, 2012). At the neonatal stage (postnatal days 7–10), rats were transiently administered MK-801, an antagonist at the NMDA receptor.…”

Section: Role For Energy Metabolismmentioning

confidence: 99%

Neural Basis for the Ability of Atypical Antipsychotic Drugs to Improve Cognition in Schizophrenia

Sumiyoshi¹,

Higuchi²,

Uehara³

2013

Front. Behav. Neurosci.

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Cognitive impairments are considered to largely affect functional outcome in patients with schizophrenia, other psychotic illnesses, or mood disorders. Specifically, there is much attention to the role of psychotropic compounds acting on serotonin (5-HT) receptors in ameliorating cognitive deficits of schizophrenia. It is noteworthy that atypical antipsychotic drugs (AAPDs), e.g., clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole, perospirone, blonanserin, and lurasidone, have variable affinities for these receptors. Among the 5-HT receptor subtypes, the 5-HT1A receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence. The neural network underlying the ability of 5-HT1A agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and gamma-aminobutyric acid neurons. A novel strategy for cognitive enhancement in psychosis may be benefited by focusing on energy metabolism in the brain. In this context, lactate plays a major role, and has been shown to protect neurons against oxidative and other stressors. In particular, our data indicate chronic treatment with tandospirone, a partial 5-HT1A agonist, recover stress-induced lactate production in the prefrontal cortex of a rat model of schizophrenia. Recent advances of electrophysiological measures, e.g., event-related potentials, and their imaging have provided insights into facilitative effects on cognition of some AAPDs acting directly or indirectly on 5-HT1A receptors. These findings are expected to promote the development of novel therapeutics for the improvement of functional outcome in people with schizophrenia.

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Effect of transient blockade of N‐methyl‐D‐aspartate receptors at neonatal stage on stress‐induced lactate metabolism in the medial prefrontal cortex of adult rats: Role of 5‐HT1A receptor agonism

Cited by 13 publications

References 77 publications

Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

Tandospirone, a 5-HT1A partial agonist, ameliorates aberrant lactate production in the prefrontal cortex of rats exposed to blockade of N-methy-D-aspartate receptors; Toward the therapeutics of cognitive impairment of schizophrenia

Neural Basis for the Ability of Atypical Antipsychotic Drugs to Improve Cognition in Schizophrenia

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