Biology subjects

Mizukami, H.

Publications and source records attributed to Mizukami, H..

4 recordsLinked to original sources

bioRxiv2023

Epileptic responses in marmosets induced by knockdown of CREB Regulated Transcription Coactivator 1 (CRTC1)

Animal models have contributed greatly to the development of anticonvulsant drugs. However, 20-30% of epilepsy patients still do not achieve adequate seizure control. It is important to understand the biological mechanisms of epilepsy in order to develop treatments and novel anticonvulsant drugs. Here we report CRTC1 knockdown (KD) induced abnormal cFOS expression beyond the injection sites followed by epileptic response by three local injections of short hairpin RNA (shRNA) in marmoset V1. Longitudinal monitoring of cortical-wide neural activity revealed transient changes in high frequency oscillations by cortical electrocorticography throughout the cortex, and a lesion in the temporal lobe was observed by MRI and postmortem histology. shCRTC1 KD marmosets showed severe lesions surrounding the injection site several months after injection. Glial cell activation may occur simultaneously or prior to IEG induction after shCRTC1 injection. Thus, the epileptic process from seizure onset to remission can be studied in this animal model.

neuroscience↗

bioRxiv2022

Imbalance of circuit plasticity and consolidation in autism model marmosets is adjusted by oxytocin administration

Alterations in the experience-dependent and autonomous elaboration of neural circuits are assumed to underlie autism spectrum disorder (ASD), though it is unclear what synaptic traits are responsible. Here, we used a valproic acid-induced ASD marmoset model, which shares common molecular features with idiopathic ASD, to investigate the structural dynamics of tuft dendrites of upper-layer pyramidal neurons and adjacent axons in the dorsomedial prefrontal cortex using two-photon microscopy. In model marmosets, dendritic spine turnover was upregulated, and spines were actively generated in clusters and subsequently survived more often than in control marmosets. Presynaptic boutons in local axons but not in commissural long-range axons showed hyperdynamic turnover in model marmosets, suggesting alterations in projection-specific plasticity. Intriguingly, nasal administration of oxytocin reduced the clustered spine emergence. Enhanced clustered spine generation, possibly unique to certain presynaptic partners, may be associated with ASD and may be a potential therapeutic target.

neuroscience↗

bioRxiv2022

Connectional architecture of the prefrontal cortex in the marmoset brain

Prefrontal cortex (PFC) has dramatically expanded in primates, but its organization and interactions with other brain regions are only partially understood. We performed high-resolution connectomic mapping of marmoset PFC and found two contrasting corticocortical and corticostriatal projection patterns: "patchy" projections that formed many columns of submillimeter scale in nearby and distant regions and "diffuse" projections that spread widely across the cortex and striatum. Parcellation-free analyses revealed representations of PFC gradients in these projections local and global distribution patterns. We also demonstrated column-scale precision of reciprocal cortico-cortical connectivity, suggesting that PFC contains a mosaic of discrete columns. Diffuse projections showed considerable diversity in the laminar patterns of axonal spread. In mice, columnar projections were much less conspicuous, underscoring the importance of the primate model. Altogether, these fine-grained analyses reveal important principles of local and long-distance PFC circuits in marmosets and provide insights into the functional organization of the primate brain.

neuroscience↗

bioRxiv2020

The Effects of Inter-Individual Biological Differences and Taphonomic Alteration on Human Bone Protein Profiles: Implications for the Development of PMI/AAD Estimation Methods

Bone proteomics studies using animal proxies and skeletonized human remains have delivered encouraging results in the search for potential biomarkers for precise and accurate post-mortem interval (PMI) and the age-at-death (AAD) estimation in medico-legal investigations. At present, however, the effects of inter-individual biological differences and taphonomic alteration on recovered human bone protein profiles are not well understood. This study investigated the human bone proteome in four human body donors studied throughout decomposition outdoors. The effects of ageing phenomena (in vivo and post-mortem), and intrinsic and extrinsic variables on the variety and abundancy of the bone proteome were assessed. Results identified a new potential biomarker for PMI estimation, as well as three potential biomarkers for AAD estimation. The results also suggest that bone mineral density (BMD) may be an important variable affecting the survival and extraction of proteins. Highlights- CO3, CO9, COBA2, CO3A1, MGP, PGS2 and TTHY are potential biomarkers for post-mortem interval estimation in skeletonized human remains - FETUA, ALBU and OLFL3 are potential biomarkers for age-at-death estimation in human remains - Taphonomic and biological variables play a significant role in survival and extraction rates of proteins in bone - Bone mineral density may affect survival of proteins in bone, probably due to the effects of the mineral matrix on the movement of decomposer microbes - Higher bone mineral density may affect the survival and the extraction rate of collagen and mineral-binding proteins

biochemistry↗