The cholinergic efferent network from the medial septal nucleus to the hippocampus has an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to efficiently encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP) induces acetylcholine synthesis in medial septal nuclei. HCNP is processed from the N-terminal region of a 186 amino acid, 21 kD HCNP precursor protein called HCNP-pp (also known as Raf kinase inhibitory protein (RKIP) and phosphatidylethanolamine-binding protein 1 (PEBP1)). In this study, we generated HCNP-pp knockout (KO) mice and assessed their cholinergic septo-hippocampal projection, local field potentials in CA1, and behavioral phenotypes. No significant behavioral phenotype was observed in HCNP-pp KO mice. However, theta power in the CA1 of HCNP-pp KO mice was significantly reduced because of fewer cholineacetyltransferase-positive axons in the CA1 stratum oriens. These observations indicated disruption of cholinergic activity in the septo-hippocampal network. Our study demonstrates that HCNP may be a cholinergic regulator in the septo-hippocampal network.

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Although several studies have demonstrated correlation between white matter hyperintensities (WMH) and impairment of executive functions, the underlying anatomical-functional relationships are not fully understood. The present study sought to investigate the correlations between the volume of WMH and medial temporal lobe atrophy (MTA) using quantitative magnetic resonance image (MRI) and a variety of executive function assessments. A total of 91 patients ranging in age from 58 to 90 years with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) or early phase AD were recruited from the outpatient clinic at the Department of Neurology of Nagoya City University Hospital. We administered neuropsychological batteries evaluating verbal memory, orientation, spatial ability, sustained attention, and a variety of executive functions, including verbal fluency, flexibility, inhibition, and working memory. Quantitative MRI analyses were performed using Dr. View/Linux software and a voxel-based specific regional analysis system. Significant correlations were observed between WMH, as well as MTA, and some executive function scores. Regression analysis revealed that MTA was the strongest predictor of flexibility and verbal fluency. These findings provide new insight into the relationship between quantitative MRI analyses and various types of executive dysfunction in elderly people with MCI due to AD and/or early phase AD. When cognitive function is examined in elderly patients with MCI due to AD or early phase AD, it is important to consider the involvement of WMH and MTA, which is indicative of AD pathology in cognitive dysfunction, particularly executive function.

BackgroundsIntramuscular injection of the SARS-CoV-2 vaccine has raised concerns about its use in patients with neuromuscular disorders (NMDs). We evaluated the response of patients with NMDs to the BNT162b2 vaccine.MethodsHealthy subjects, patients with spinal muscular atrophy (SMA), and patients with Duchenne muscular dystrophy (DMD) were included. All participants received two BNT162b2 doses. SARS-CoV-2 antibody titers at baseline and 2 weeks after each vaccination were compared between groups. Residual muscle volume was evaluated in NMDs group. A questionnaire documented adverse reactions.ResultsEleven patients with NMDs (9 with SMA, 2 with DMD; 7 males; aged 32.7 ± 19.3 years) and 346 healthy subjects (60 males, aged 40.0 ± 12.4 years) were included. Antibody titers (U/mL) were similar between groups (baseline: <0.40 vs. <0.40, first vaccination, 145 ± 258 vs. 103 ± 1192, and second vaccination, 1528 ± 1265 vs. 1429 ± 944; p = 1.000, 0.909, and 0.736, respectively). A negative correlation was found between antibody titers and residual muscle volume but was not significant (Mercuri scale, r = −0.429, p = 0.249; fat infiltration rate, r = −0.194, p = 0.618). The adverse reactions were comparable between groups.ConclusionThe BNT162b2 vaccine is safe and effective in patients with NMDs.