Alteration of Neuregulin 1/Erbb4 in Absence Epilepsy: Regulatory Effect on TRPV1 Expression

The footprint of Neuregulin 1 (NRG1) / ERbB4 in the pathophysiology of some neurological disorders and TRPV1 regulation has been indicated. The alterations of NRG1 and ErbB4 as well as TRPV1 signaling pathway was investigated during development of absence epilepsy in the genetic animal model of absence epilepsy. Male WAG/Rij and Wistar rats were divided into four experimental groups of 2 and 6 months of age. The protein level of NRG1, ERbB4 and TRPV1 were measured in the somatosensory cortex and hippocampus. The cortical protein level of NRG1 and ErbB4 in the 6-month-old WAG/Rij rats was lower than Wistar rats. Protein level of TRPV1 was lower in 2- and 6-month-old WAG/Rij rats compared to age-matched Wistar rats. Hippocampal protein level of NRG1 in 6-month-old WAG/Rij rats was lower than 2-month-old WAG/Rij rats. Low level of ErbB4 protein in 2-month-old and high level in 6-month-old WAG/Rij rats was shown compared to Wistar rats. Protein level of TRPV1 was lower in the 2-month-old and higher in 6-month- old WAG/Rij rats compared to age-matched Wistar rats. Furthermore, high correlation between NRG1/ERbB4 and TRPV1 expressions in the cortex and hippocampus was indicated. The expression of NRG1/ERbB4 and TRPV1 followed a similar pattern during life span of Wistar and WAG/Rij rats.Our findings indicated the potential role of NRG1/ErbB4 pathway as well as TRPV1 in the pathogenesis of absence epilepsy. The regulatory effect of ERbB4 receptor on the TRPV1 expression has been suggested following by the similarity pattern of expression.

Neuregulin signaling mediates the acute and sustained antidepressant effects of subanesthetic ketamine

Subanesthetic ketamine evokes rapid antidepressant effects in human patients that persist long past ketamine’s chemical half-life of ~2 h. Ketamine’s sustained antidepressant action may be due to modulation of cortical plasticity. We find that ketamine ameliorates depression-like behavior in the forced swim test in adult mice, and this depends on parvalbumin-expressing (PV) neuron-directed neuregulin-1 (NRG1)/ErbB4 signaling. Ketamine rapidly downregulates NRG1 expression in PV inhibitory neurons in mouse medial prefrontal cortex (mPFC) following a single low-dose ketamine treatment. This NRG1 downregulation in PV neurons co-tracks with the decreases in synaptic inhibition to mPFC excitatory neurons for up to a week. This results from reduced synaptic excitation to PV neurons, and is blocked by exogenous NRG1 as well as by PV targeted ErbB4 receptor knockout. Thus, we conceptualize that ketamine’s effects are mediated through rapid and sustained cortical disinhibition via PV-specific NRG1 signaling. Our findings reveal a novel neural plasticity-based mechanism for ketamine’s acute and long-lasting antidepressant effects.

ErbB4 Receptors in the Medial Habenula Regulate Contextual Fear Memory

The Medial Habenular (MHb) and the Lateral Habenular nuclei are 2 main parts of the habenular complex (Hb). Recent studies showed that MHb plays an important role in memory, and in the expression of ErbB4. However, the expression of MHb ErbB4 receptor and its role in fear memory is not well understood. In this study, western blotting and quantitative real-time polymerase chain reaction were used to assess the protein and mRNA levels of ErbB4 in the process of contextual fear conditioning. A pharmacological approach was used to block and stimulate the ErbB4 receptor. Contextual fear conditioning tests induced a significant increase on the expression of ErbB4 at various times in the Hb and the MHb. Moreover, the blockade and stimulation of MHb ErbB4 receptors did not affect the fear formation but impaired and improved the contextual-dependent fear expression. Furthermore, in vitro electrophysiological recordings showed that the blockade of the MHb ErbB4 receptor reduced the presynaptic gamma-amino butyric acid release. ErbB4 is a susceptible gene for schizophrenia and the above findings may provide new insights into the mechanisms of fear-related responses.

Neuregulin-1 exerts molecular control over axolotl lung regeneration through ErbB family receptors

ABSTRACTThe induction of new lung tissue after disease or trauma has the potential to save lives and transform patient outcomes. Ambystoma mexicanum, the axolotl salamander, is a classic model organism used to study vertebrate regeneration, primarily after limb amputation. While it is hypothesized that axolotls regenerate all of their tissues, exploration of lung regeneration has not been performed until now. Proliferation after lung injury was observed to be a global response, suggesting that regeneration utilizes a compensatory mechanism, in contrast to limb regeneration’s epimorphic response. ErbB signaling is crucial for the proliferative response during lung regeneration, likely through the ErbB2:ErbB4 receptor heterodimer. ErbB4 mRNA was found to be highly upregulated at both one and three weeks post amputation. Neuregulin-1p (NRG1) can induce proliferation in the lung and likely exerts molecular control over lung regeneration. Inhibition of ErbB2 was sufficient to both block regeneration and the proliferative response observed after NRG1 treatment.