Amyloban, extracted from Hericium erinaceus, ameliorates social deficits and suppresses the enhanced dopaminergic system in social defeat stress mice.

Social dysfunctions are common in various psychiatric disorders, including depression, schizophrenia, and autism, and are long-lasting and difficult to treat. The development of treatments for social impairment is critical for the treatment of several psychiatric disorders. "Amyloban 3399," a product extracted from the mushroom Hericium erinaceus, markedly improves social dysfunctions in patients with treatment-resistant schizophrenia and depression. However, the molecular mechanism(s) through which amyloban ameliorates social impairment remains unclear. To clarify this mechanism, in this study, we aimed to establish a mouse model of social defeat stress (SDS) and investigate the effects of amyloban on social deficits. Amyloban administration ameliorated social deficits and the dopamine system activity in SDS mice. These findings suggest that there is a possibility that amyloban may improve social deficits by suppressing the hyperactivation of the dopaminergic system. Amyloban may be an effective treatment for social dysfunctions associated with various psychiatric disorders.

Involvement of Denervated Midbrain-Derived Factors in the Formation of Ectopic Cortico-Mesencephalic Projection after Hemispherectomy.

Neuronal remodeling after brain injury is essential for functional recovery. After unilateral cortical lesion, axons from the intact cortex ectopically project to the denervated midbrain, but the molecular mechanisms remain largely unknown. To address this issue, we examined gene expression profiles in denervated and intact mouse midbrains after hemispherectomy at early developmental stages using mice of either sex, when ectopic contralateral projection occurs robustly. The analysis showed that various axon growth-related genes were upregulated in the denervated midbrain, and most of these genes are reportedly expressed by glial cells. To identify the underlying molecules, the receptors for candidate upregulated molecules were knocked out in layer 5 projection neurons in the intact cortex, using the CRISPR/Cas9-mediated method, and axonal projection from the knocked-out cortical neurons was examined after hemispherectomy. We found that the ectopic projection was significantly reduced when integrin subunit ß three or neurotrophic receptor tyrosine kinase 2 (also known as TrkB) was knocked out. Overall, the present study suggests that denervated midbrain-derived glial factors contribute to lesion-induced remodeling of the cortico-mesencephalic projection via these receptors.SIGNIFICANCE STATEMENT After brain injury, compensatory neural circuits are established that contribute to functional recovery. However, little is known about the intrinsic mechanism that underlies the injury-induced remodeling. We found that after unilateral cortical ablation expression of axon-growth promoting factors is elevated in the denervated midbrain and is involved in the formation of ectopic axonal projection from the intact cortex. Evidence further demonstrated that these factors are expressed by astrocytes and microglia, which are activated in the denervated midbrain. Thus, our present study provides a new insight into the mechanism of lesion-induced axonal remodeling and further therapeutic strategies after brain injury.