Biology subjects

Shautidze, G.

Publications and source records attributed to Shautidze, G..

3 recordsLinked to original sources

bioRxiv2026

Sex-specific effects of exercise on motor coordination and extended basal ganglia physiology.

Exercise broadly affects the basal ganglia, brain structures involved in motor coordination. Exercise-induced changes in these regions can improve pathological conditions such as Parkinsons disease and substance use disorders. Importantly, biological sex is a significant factor in the effects of exercise and in the presentation of these basal ganglia-related conditions. Here, we find surprising sex differences in exercises influence over motor coordination and neural activity across three extended basal ganglia structures: dorsomedial striatum cholinergic interneurons (CINs), substantia nigra pars compacta (SNc) dopaminergic neurons, and caudal pedunculopontine nucleus (PPN) cholinergic neurons. Using voluntary wheel running, accelerating rotarod, ex vivo electrophysiology, and morphological reconstructions, we found that exercise enhances motor coordination, increases SNc excitability, and strengthens excitatory input onto the PPN selectively in female mice. By contrast, exercise increases spontaneous firing rate and reduces dendritic complexity selectively in male CINs. These data reveal sex-specific exercise effects correlated across behavioral and cellular levels. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=192 SRC="FIGDIR/small/720719v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@d0f755org.highwire.dtl.DTLVardef@11e2335org.highwire.dtl.DTLVardef@199a591org.highwire.dtl.DTLVardef@44e4d9_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIOne week of exercise enhances motor coordination in females but not males C_LIO_LIExercise increases SNc excitability and excitatory input onto the PPN in females C_LIO_LIExercise increases dorsomedial striatal cholinergic neurons activity in males C_LIO_LIBaseline sex differences in morphology of striatal cholinergic and SNc neurons C_LI

neuroscience↗

bioRxiv2026

Intravenous anti-abeta immunotherapy acutely increases cerebral amyloid angiopathy and vascular damages in APOE4 mice

Anti-A{beta} immunotherapies for Alzheimers Disease (AD) have high rates of amyloid-related imaging abnormalities (ARIA), an adverse side effect with markedly higher rates in APOE4 carriers. We developed a mouse model of ARIA centered on human APOE3 and APOE4 genotypes with amyloidosis (5xFAD transgene) and microglia tagged with green fluorescent protein (from the CX3CR1 promoter). We measured acute changes following a single intravenous treatment with 3D6 anti-A{beta} immunotherapy. Across 82 mice, APOE4 mice showed stepwise reductions in the number of plaques from one to ten days, with significant reductions in the subiculum (48%) and thalamus (40%) at ten days. There was no significant reduction in APOE3 mice. There was a concomitant significant increase in deposition of cerebral amyloid angiopathy (CAA) in APOE4 mice at one (76%) and three (51%) days in leptomeningeal vessels. The increased CAA correlated with a significant 189% increase in A{beta} within microglia of APOE4 (but not APOE3) mice at one day. Smooth muscle actin staining showed significant 58% reduction near CAA. MRI analysis revealed a significant 32% increase in microhemorrhages ten days following treatment. These data demonstrate an APOE4-specific redistribution of parenchymal amyloid to CAA by 3D6 within days, leading to increased vascular damages associated with ARIA.

neuroscience↗

bioRxiv2025

Varied monoamine reuptake inhibitors reduce parvalbumin expression; implications for pyramidal cell disinhibition and enhanced neuroplasticity

First-line antidepressants are effective in a significant percent of individuals but a full understanding of how these therapeutics target specific endpoints is lacking. Prior work has shown that depression is associated with hippocampal atrophy and that antidepressants can increase neurotrophin levels to increase hippocampal neurogenesis as well as hippocampal pyramidal cell (PC) spine density and arbor. These effects likely contribute to amelioration of symptoms. A less well-explored possibility is that antidepressants concomitantly disinhibit hippocampal PC activity, which could also facilitate increased PC arbor, spinogenesis and/or activity. In accordance, previous studies have shown antidepressants can attenuate stress-induced upregulation of perineuronal nets (PNNs). PNNs are predominantly localized to parvalbumin (PV) expressing GABAergic interneurons and increase PV expression and neuronal activity. Though specific antidepressants have been explored for effects on regional PNN expression, the question of whether hippocampal PNN/ECM remodeling is a shared feature of varied antidepressant drugs and more importantly, of whether it is associated with significant hippocampal PV inhibition, has not been well-addressed. Herein we examine three monoamine reuptake inhibitors, fluoxetine, venlafaxine and viloxazine, in animal models for effects on PNN remodeling and PV expression, a proxy for PV activity. We observe shared effects of these therapeutics including the ability to increase PNN degrading effectors that can downregulate PV activity. Consistent with this, we observe shared effects of these drugs in terms of their ability to significantly reduce PV levels. These findings highlight the possibility that ECM remodeling and associated hippocampal PC disinhibition represent a shared feature of varied antidepressant medications.

neuroscience↗