Direct Enhancement Effect of Hippocampal Cholinergic Neurostimulating Peptide on Cholinergic Activity in the Hippocampus

• Published in: International journal of molecular sciences Vol. 24; no. 10; p. 8916
• Main Authors: Madokoro, Yuta, Kato, Daisuke, Tsuda, Yo, Arakawa, Itsumi, Suzuki, Kengo, Sato, Toyohiro, Mizuno, Masayuki, Uchida, Yuto, Ojika, Kosei, Matsukawa, Noriyuki
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.05.2023; MDPI
• Subjects: Acetyltransferase; Alzheimer's disease; Animals; Choline; choline acetyltransferase; Choline O-acetyltransferase; Choline O-Acetyltransferase - genetics; Choline O-Acetyltransferase - metabolism; Cholinergic Agents - metabolism; Cholinergics; Communication; Dementia; Dementia disorders; Electrophysiological recording; Growth factors; hippocampal cholinergic neurostimulating peptide; hippocampal cholinergic neurostimulating peptide precursor protein; hippocampal HCNP-pp conditional KO mouse model; Hippocampus; Hippocampus - metabolism; Lewy bodies; local field potential; Memory; Mice; Nerve growth factor; Nerve Growth Factor - metabolism; Neurological diseases; Neuropeptides - metabolism; Peptides; theta oscillation; TrkA protein; TrkA receptors; Ventricle; Ventricles (cerebral); Japan; local field potential; theta oscillation; choline acetyltransferase; nerve growth factor; hippocampal HCNP-pp conditional KO mouse model; hippocampal cholinergic neurostimulating peptide precursor protein; hippocampal cholinergic neurostimulating peptide
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24108916

The cholinergic efferent network from the medial septal nucleus to the hippocampus is crucial for learning and memory. This study aimed to clarify whether hippocampal cholinergic neurostimulating peptide (HCNP) has a rescue function in the cholinergic dysfunction of HCNP precursor protein (HCNP-pp) conditional knockout (cKO). Chemically synthesized HCNP or a vehicle were continuously administered into the cerebral ventricle of HCNP-pp cKO mice and littermate floxed (control) mice for two weeks via osmotic pumps. We immunohistochemically measured the cholinergic axon volume in the stratum oriens and functionally evaluated the local field potential in the CA1. Furthermore, choline acetyltransferase (ChAT) and nerve growth factor (NGF) receptor (TrkA and p75NTR) abundances were quantified in wild-type (WT) mice administered HCNP or the vehicle. As a result, HCNP administration morphologically increased the cholinergic axonal volume and electrophysiological theta power in HCNP-pp cKO and control mice. Following the administration of HCNP to WT mice, TrkA and p75NTR levels also decreased significantly. These data suggest that extrinsic HCNP may compensate for the reduced cholinergic axonal volume and theta power in HCNP-pp cKO mice. HCNP may function complementarily to NGF in the cholinergic network in vivo. HCNP may represent a therapeutic candidate for neurological diseases with cholinergic dysfunction, e.g., Alzheimer's disease and Lewy body dementia.