Biology subjects

Horie, S.

Publications and source records attributed to Horie, S..

5 recordsLinked to original sources

bioRxiv2025

Age-related decline of synaptic plasticity is regulated by neuro-androgen and neuro-estrogen in normal aging of hippocampus

We revealed a good relationship between age-dependent decrease in the hippocampal dendritic spine density and age-dependent decrease in hippocampal androgen and estrogen levels with normal aging of male rats. Approximately 25% decrease in the spine density was observed in hippocampal CA1 region by going from 3 month-old (3m; young adult) to 24 month-old (24m; aged). We found a significant age-induced decrease in hippocampal neuro-androgen levels by going from 3m to 24 m using mass-spectrometric analysis. The hippocampal levels of testosterone (T) and dihydrotestosterone (DHT) dramatically decreased from 17 nM T and 7 nM DHT at 3 m to 17/100 nM T and 7/15 nM DHT at 24 m. On the other hand, hippocampal estradiol (E2) was moderately decreased with aging, from 8 nM at 3 m to 2 nM at 24m. Comprehensive analysis of mRNAs of hippocampal steroidogenic enzymes and receptors showed an age-dependent decrease in their expression levels by approximately 50% (P450(17)), 25% (17-hydroxysteroid dehydrogenase) and 0% (5-reductase and P450arom). Androgen receptor AR was moderately decreased but estrogen receptor ER was not decreased with aging. The 25% decrease in the spine density with aging may be due to a balance between considerably decreased T and DHT levels (spine decrease factor) and remained moderately high E2 level (spine increase factor) in the 24m hippocampus. Aged hippocampus still has moderate capacity of sex-steroid synthesis and their functions. Interestingly, DHT-supplementation and T-supplementation recovered the spine density at 24m.

neuroscience↗

bioRxiv2025

Rethinking synthesis and function of neuro-estrogen and neuro-androgen in the hippocampus: some methodological problems and possible solutions

Local synthesis and action of neuro-estrogen and neuro-androgen (including neuro-estradiol (nE2) and neuro-testosterone (nT) have become recognized as key mechanisms in modulation of neural plasticity and cognitive performance, in addition to the contribution of circulating sex steroids. However, still several methodological problems are left to be solved in order to get an better understanding of functions of neural sex steroids in the brain. Here we describe and discuss important improvements in the methods for determination of accurate concentrations of nE2 and nT in rat hippocampus (Section 1), and in methods for analysis of the dendritic spine density in castrated male rat hippocampus (Section 2). The improvements are discussed in order to solve the following two problems. One problem is that the previously reported nE2 concentrations in the hippocampus were widely distributed between [~]3 pg/g tissue and [~]2 ng/g tissue (i.e., between [~]11 pM and [~]7 nM) (Section 1). The other problem is that the degree of decrease in hippocampal spine density by castration in male rat hippocamps was strongly dependent on surgical skills of operators (surgeons) (Section 2).

neuroscience↗

bioRxiv2024

Inhibition of PDE5 induces rapid non-genomic increase in hippocampal dendritic spines via specific kinases

Cyclic guanosine monophosphate (cGMP) is a typical neuromodulator that is used in neuronal synapses. Inhibitor of phosphodiesterase 5 (PDE5) could regulates signaling pathways by elevating cGMP levels. In the current study, we found that the treatments with tadalafil, a PDE5 inhibitor, for 2 h rapidly and non-genomically increased the total density of dendritic spines, using confocal imaging of Lucifer Yellow-injected hippocampal CA1 pyramidal neurons. Since inhibition of PDE5 elevates cGMP levels at synapses, we analyzed downstream nongenomic signaling. We analyzed the involvement of kinase signaling, because rapid postsynaptic modulation often involves kinase networks as observed from many investigations of synaptic functions. Upon co-treatments of PKG inhibitor (KT5823) with tadalafil, the spine increase was considerably blocked. In addition, co-treatments of GSK-3 inhibitor (I8) also blocked the spine increase induced by tadalafil. However, inhibitors of other representative synaptic kinases, including LIMK, Erk/MAPK, PKA, PKC and PI3K, did not suppress the tadalafil-induced spine increases. PDE5 inhibitors have attracted attention on their recovery effects from pathological damages, including memory improvement from cognitive impairment by Stroke, Amyloid beta accumulation and tau phosphorylation. The current finding of tadalafil function about rapid modulation of neural plasticity may add new elemental steps of anti-aging capacity against cognitive decline.

neuroscience↗

bioRxiv2024

Synaptic targets and cellular sources of CB1 cannabinoid receptor and vesicular glutamate transporter-3 expressing nerve terminals in relation to GABAergic neurons in the human cerebral cortex

Cannabinoid receptor 1 (CB1) regulates synaptic transmission through presynaptic receptors in nerve terminals, and its physiological roles are of clinical relevance. The cellular sources and synaptic targets of CB1-expressing terminals in the human cerebral cortex are undefined. We demonstrate a variable laminar pattern of CB1-immunorective axons and electron microscopically show that CB1-positive GABAergic terminals make type-2 synapses innervating dendritic shafts (69%), dendritic spines (20%) and somata (11%) in neocortical layers 2-3. Of the CB1-immunopositive GABAergic terminals, 25% were vesicular-glutamate-transporter-3 (VGLUT3)-immunoreactive, suggesting GABAergic/glutamatergic co-transmission on dendritic shafts. In vitro recorded and labelled VGLUT3 or CB1-positive GABAergic interneurons expressed cholecystokinin, vasoactive-intestinal-polypeptide and calretinin, had diverse firing, axons and dendrites, and included rosehip, neurogliaform and basket cells, but not double bouquet or axo-axonic cells. CB1-positive interneurons innervated pyramidal cells and GABAergic interneurons. Most glutamatergic synaptic terminals formed type-1 synapses and some were positive for CB1 receptor concentrated in the presynaptic active zone, unlike in GABAergic terminals. From the sampled VGLUT3-positive terminals, 60% formed type-1 synapses with dendritic spines (80%) or shafts (20%) and 52% were also positive for VGLUT1, suggesting intracortical origin. Some VGLUT3-positive terminals were immunopositive for vesicular-monoamine-transporter-2, suggesting 5-HT/glutamate co-transmission. Overall, the results show that CB1 regulates GABA release mainly to dendritic shafts of both pyramidal cells and interneurons, and predict CB1-regulated co-release of GABA and glutamate from single cortical interneurons. We also demonstrate the co-existence of multiple vesicular glutamate transporters in a select population of terminals probably originating from cortical neurons and innervating dendritic spines in the human cerebral cortex.

neuroscience↗

bioRxiv2022

Differential effects of group III metabotropic glutamate receptors on spontaneous inhibitory synaptic currents in spine-innervating double bouquet and parvalbumin-expressing dendrite-targeting GABAergic interneurons in human neocortex

Diverse neocortical GABAergic neurons specialise in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III mGluRs by L-AP4 changes GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in two distinct dendritic spine-innervating GABAergic interneurons recorded in vitro in human neocortex. Calbindin-positive double bouquet cells (DBC) had columnar "horsetail" axons descending through layers II-V innervating dendritic spines (48%) and shafts, but not somata of pyramidal and non-pyramidal neurons. Parvalbumin-expressing dendrite-targeting cell (PV-DTC) axons extended in all directions innervating dendritic spines (22%), shafts (65%) and somata (13%). As measured, 20% of GABAergic neuropil synapses innervate spines, hence DBCs, but not PV-DTCs, preferentially select spine targets. Group III mGluR activation paradoxically increased the frequency of sIPSCs in DBCs (to median 137% of baseline), but suppressed it in PV-DTCs (median 92%), leaving the amplitude unchanged. The facilitation of sIPSCs in DBCs may result from their unique GABAergic input being disinhibited via network effect. We conclude that dendritic spines receive specialised, diverse GABAergic inputs, and group III mGluRs differentially regulate GABAergic synaptic transmission to distinct GABAergic cell types in human cortex.

neuroscience↗