In situ hybridization reveals developmental regulation of ErbB1-4 mRNA expression in mouse midbrain: Implication of ErbB receptors for dopaminergic neurons

Abe, Yuichi; Namba, Hisaaki; Zheng, Yingjun; Nawa, Hiroyuki

doi:10.1016/j.neuroscience.2009.03.022

Cited by 85 publications

(89 citation statements)

References 72 publications

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“…20,21 Our in situ hybridization detected high levels of ErbB4 mRNA signals in almost all midbrain dopaminergic neurons. In particular, the expression is higher from the late embryonic stage to neonatal stage when these neurons are vigorously developing.…”

Section: Introductionmentioning

confidence: 73%

Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic states in adulthood: implication in neurodevelopmental hypothesis for schizophrenia

et al. 2010

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Neuregulin-1 (NRG1) is implicated in the etiology or pathology of schizophrenia, although its biological roles in this illness are not fully understood. Human midbrain dopaminergic neurons highly express NRG1 receptors (ErbB4). To test its neuropathological role in the neurodevelopmental hypothesis of schizophrenia, we administered type-1 NRG1 protein to neonatal mice and evaluated the immediate and subsequent effects on dopaminergic neurons and their associated behaviors. Peripheral NRG1 administration activated midbrain ErbB4 and elevated the expression, phosphorylation and enzyme activity of tyrosine hydroxylase (TH), which ultimately increased dopamine levels. The hyperdopaminergic state was sustained in the medial prefrontal cortex after puberty. There were marked increases in dopaminergic terminals and TH levels. In agreement, higher amounts of dopamine were released from this brain region of NRG1-treated mice following high potassium stimulation. Furthermore, NRG1-treated mice exhibited behavioral impairments in prepulse inhibition, latent inhibition, social behaviors and hypersensitivity to methamphetamine. However, there were no gross abnormalities in brain structures or other phenotypic features of neurons and glial cells. Collectively, our findings provide novel insights into neurotrophic contribution of NRG1 to dopaminergic maldevelopment and schizophrenia pathogenesis.

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Section: Introductionmentioning

confidence: 73%

Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic states in adulthood: implication in neurodevelopmental hypothesis for schizophrenia

et al. 2010

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“…In situ hybridization was performed as described previously (Abe et al, 2009). Mice at P18 were transcardially perfused with 4% paraformaldehyde in 0.1 M sodium phosphate buffer, pH 7.4.…”

Section: Methodsmentioning

confidence: 99%

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

Abe¹,

Namba²,

Kato³

et al. 2011

J. Neurosci.

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Neuregulin-1 (NRG1) signaling is thought to contribute to both neuronal development and schizophrenia neuropathology. Here, we describe the developmental effects of excessive peripheral NRG1 signals on synaptic activity and AMPA receptor expression of GABAergic interneurons in postnatal rodent neocortex. A core peptide common to all NRG1 variants (eNRG1) was subcutaneously administered to mouse pups. Injected eNRG1 penetrated the blood-brain barrier and activated ErbB4 NRG1 receptors in the neocortex, in which ErbB4 mRNA is predominantly expressed by parvalbumin-positive GABAergic interneurons. We prepared neocortical slices from juvenile mice that were receiving eNRG1 subchronically and recorded inhibitory synaptic activity from layer V pyramidal neurons. Postnatal eNRG1 treatment significantly enhanced polysynaptic IPSCs, although monosynaptic IPSCs were not affected. Examination of excitatory inputs to parvalbumin-containing GABAergic interneurons revealed that eNRG1 treatment significantly increased AMPA-triggered inward currents and the amplitudes and frequencies of miniature EPSCs (mEPSCs). Similar effects on mEPSCs were observed in mice treated with a soluble, full-length form of NRG1 type I. Consistent with the electrophysiologic data, expression of the AMPA receptor GluA1 (i.e., GluR1, GluRA) was upregulated in the postsynaptic density/cytoskeletal fraction prepared from eNRG1-treated mouse neocortices. Cortical GABAergic neurons cultured with eNRG1 exhibited a significant increase in surface GluA1 immunoreactivity at putative synaptic sites on their dendrites. These results indicate that NRG1 circulating in the periphery influences postnatal development of synaptic AMPA receptor expression in cortical GABAergic interneurons and may play a role in conditions characterized by GABA-associated neuropathologic processes.

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“…RBANS is composed of 12 subtests used to calculate five age-adjusted index scores and a total score [39]. Test indices are: immediate memory (composed of list learning and story memory tasks); visuospatial/constructional (composed of figure copy and line orientation tasks); language (composed of picture naming and semantic fluency tasks); attention (composed of digit span and coding tasks); and delayed memory (composed of list recall, story recall, figure recall, and list recognition tasks).…”

Section: Cognitive Measuresmentioning

confidence: 99%

Gender differences in cognitive deficits in schizophrenia with and without diabetes

Zhang

Han

Zhang

et al. 2015

Comprehensive Psychiatry

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This study investigated gender differences in cognition in schizophrenia with and without diabetes. Cognition was assessed in 263 individuals with schizophrenia with age range (40-68): 67 males and 34 females with schizophrenia with diabetes; and 125 males and 37 females with schizophrenia without diabetes according to the repeatable battery for the assessment of neuropsychological status (RBANS). Fasting glucose, hemoglobin A1c (HbA1c) and lipid levels were measured. Results showed that male individuals performed worse on most cognitive tasks, especially attention, in schizophrenia with than without diabetes. This result was not observed in female individuals. Also, individuals of both genders showed higher fasting glucose and HbA1c in schizophrenia with than without diabetes. In schizophrenia with diabetes, males had significantly worse cognition than females in all cognitive domains. Higher HbA1c, lower high-density lipoprotein, and an earlier age of onset of schizophrenia were found in males compared with female individuals. HbA1c was negatively associated with attention and the RBANS total score for males but not for females. In schizophrenia without diabetes, males showed worse performance in immediate and delayed memory than females. This study support cognition was worse for males with schizophrenia irrespective of whether they have diabetes or not. However, diabetes exemplified the gender differences, especially in attention. Disciplines Medicine and Health Sciences Publication DetailsZhang, B., Han, M., Zhang, X., Hui, L., Jiang, S., Yang, F., Tan 1 Both authors contributed equally to this work.Running title: Gender differences in cognition in schizophrenia ABSTRACTThis study investigated gender differences in cognition in schizophrenia with and without diabetes. Cognition was assessed in 263 individuals with schizophrenia with age range (40-68): 67 males and 34 females with schizophrenia with diabetes; and 125 males and 37 females with schizophrenia without diabetes according to the repeatable battery for the assessment of neuropsychological status (RBANS). Fasting glucose, hemoglobin A1c(HbA1c) and lipid levels were measured. Results showed that male individuals performed worse on most cognitive tasks, especially attention, in schizophrenia with than without diabetes. This result was not observed in female individuals. Also, individuals of both genders showed higher fasting glucose and HbA1c in schizophrenia with than without diabetes. In schizophrenia with diabetes, males had significantly worse cognition than females in all cognitive domains. Higher HbA1c, lower high-density lipoprotein, and an earlier age of onset of schizophrenia were found in males compared with female individuals.HbA1c was negatively associated with attention and the RBANS total score for males but not for females. In schizophrenia without diabetes, males showed worse performance in immediate and delayed memory than females. This study support cognition was worse for males with schizophrenia irrespective of whether the...

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In situ hybridization reveals developmental regulation of ErbB1-4 mRNA expression in mouse midbrain: Implication of ErbB receptors for dopaminergic neurons

Cited by 85 publications

References 72 publications

Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic states in adulthood: implication in neurodevelopmental hypothesis for schizophrenia

Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic states in adulthood: implication in neurodevelopmental hypothesis for schizophrenia

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

Gender differences in cognitive deficits in schizophrenia with and without diabetes

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