Biology subjects

Bradshaw, H.

Publications and source records attributed to Bradshaw, H..

5 recordsLinked to original sources

bioRxiv2026

Perinatal cannabidiol exposure reshapes astrocyte morphology and tripartite synapse organization in a sex-dependent manner

Cannabidiol (CBD) has recently gained significant public acceptance as a safe therapeutic, contributing to increased use during pregnancy. However, little is known about how maternal CBD exposure impacts fetal brain development. Here, we established a preclinical CBD perinatal exposure (CBD-PCE) model to examine the impacts of CBD on astrocyte morphology in the medial prefrontal cortex (mPFC), a brain region critical for working memory and affective behaviors. Astrocytes play critical roles in maintaining ionic/metabolic homeostasis, neurotransmission, and neurovascular coupling in the CNS. They exhibit highly ramified processes with endfeet surrounding synapses, forming tripartite synapses. We quantitatively assessed the impact of CBD-PCE on astrocyte morphology and the composition of tripartite synapses in mPFC using high-resolution three-dimensional (3D) imaging. Our morphometric analyses revealed that CBD-PCE reduced astrocyte density and increased the number of major branches and whole-cell volume in the mPFC of male, but not female, progenies. Using high-magnification 3D analysis, we found that mPFC astrocytes after CBD-PCE exhibited increased neuropil infiltration volume and reduced surface-to-volume ratios in males but not in females. Moreover, the levels of aquaporin-4 (AQP4) and Kir4.1 inwardly rectifying potassium channel, two key components in regulating ionic homeostasis, are elevated on the membranes of male CBD-PCE astrocytes. We also analyzed mPFC tripartite synapses and observed significant increases in thalamocortical tripartite synapse density in both sexes, whereas intracortical excitatory synapses were reduced only in females. Collectively, these findings demonstrate that CBD-PCE induces sex-specific changes in astrocyte morphology and in the composition of tripartite synapses in the mPFC of the progenys brains.

neuroscience↗

bioRxiv2025

Acetaminophen inhibits diacylglycerol lipase synthesis of 2-arachidonoyl glycerol: implications for nociception

SUMMARYThough acetaminophen is a ubiquitous analgesic, its mechanism of action remains unknown. Thus, even though acetaminophen causes ∼500 deaths each year in the US it has not been possible to design safer alternatives. Because endocannabinoids may have a role in acetaminophen action, we examined interactions between the two. We now report that acetaminophen inhibits the activity of diacylglycerol lipase α (DAGLα), but not DAGLβ, decreasing production of the endocannabinoid 2-arachidonoyl glycerol. This gave rise to the counterintuitive hypothesis that decreasing endocannabinoid production by DAGLαinhibitionmay be antinociceptive in certain settings. Supporting this hypothesis, we find that DAGL inhibition by RHC80267 is antinociceptive in wildtype but not CB1 knockout mice in the hotplate test. We propose 1) that activation of DAGLα may exacerbate some forms of nociception and 2) a novel mechanism for the antinociceptive actions of acetaminophen whereby acetaminophen inhibits a DAGLα/CB1-based circuit that plays a permissive role in at least one form of nociception.

neuroscience↗

bioRxiv2025

Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats.

Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of psilocybin in fully awake, drug naive rats. Female and male rats were given IP injections of vehicle or psilocybin in doses of 0.03 mg/kg, 0.3 mg/kg, and 3.0 mg/kg while fully awake during the imaging session. Changes in BOLD signal were recorded over a 20 min window. Data for resting state functional connectivity were collected approximately 35 min post injection All data were registered to rat 3D MRI atlas with 173 brain regions providing site-specific changes in global brain activity and changes in functional connectivity. Treatment with psilocybin resulted in a significant dose-dependent increase in positive BOLD signal. The areas most affected by the acute presentation of psilocybin were the somatosensory cortex, basal ganglia and thalamus. Females were significantly more sensitive to the 0.3 mg/kg dose of psilocybin than males. There was a significant dose-dependent global increase in functional connectivity, highlighted by hyperconnectivity to the cerebellum. Brain areas hypothesized to be involved in loss of sensory filtering and organization of sensory motor stimuli such as the claustrum and the cortico-basal ganglia-thalamic-cortical loop were all affected by psilocybin in a dose-dependent manner. Indeed, the general neuroanatomical circuitry associated with the psychedelic experience was affected but the direction of the BOLD signal and pattern of activity between neural networks was inconsistent with the human literature.

neuroscience↗

bioRxiv2019

Long-Term Aberrations To Cerebellar Endocannabinoids Induced By Early-Life Stress

Studies of early-life stress traditionally focus on glucocorticoid signaling as a modulator of neurodevelopmental risk, but emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling. Existing studies on stress-induced endocannabinoid dysregulation have focused on changes to cerebrum that are temporally proximal to stressors, but little is known about temporally distal effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Further, sex-specific effects of stress on cerebellar endocannabinoid tone are understudied. Following a naturalistic rodent model of early-life stress, limited bedding at postnatal days 2-9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids and related lipids and mRNA were assessed, and behavioral performance was evaluated. Regional and sex-specific effects were present at baseline and following early-life stress. Limited bedding impaired peripherally-measured basal corticosterone in adult males only. In the CNS, early-life stress (1) decreased 2-arachidonoyl glycerol and arachidonic acid in the cerebellar deep nuclei in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Transcriptomics for cerebellar interpositus nucleus revealed substantial sex effects, with minimal effects of stress. Stress did impair novel object recognition in both sexes and social preference in females. Taken together, the cerebellar endocannabinoids system exhibits robust sex-specific differences, malleable through early-life stress and perhaps also contributing to sexual differentiation of the brain. The current study may foster future research into stress as a risk factor for cerebellar-related dysfunctions.

neuroscience↗

bioRxiv2016

Low plastic ingestion rate in Atlantic Cod (Gadus morhua) from Newfoundland destined for human consumption collected through citizen science methods

Marine microplastics are a contaminant of concern because their small size allows ingestion by a wide range of marine life. Using citizen science during the Newfoundland recreational cod fishery, we sampled 205 Atlantic cod (Gadus morhua) destined for human consumption and found that 5 had eaten plastic, an ingestion prevalence rate of 2.4%. This ingestion rate for Atlantic cod is the second lowest recorded rate in the reviewed published literature (the lowest is 1.4%), and the lowest for any fish in the North Atlantic. This is the first report for plastic ingestion in fish in Newfoundland, Canada, a province dependent on fish for sustenance and livelihoods.\n\nHighlights (3-5 points, 85 char max including spaces)O_LIPlastic ingestion rate of 2.4% for Atlantic Cod (n=205)\nC_LIO_LIFirst recorded baseline for fish in Newfoundland, Canada\nC_LIO_LIThis plastic ingestion prevalence rate is among the lowest recorded to date\nC_LIO_LIUsed citizen science to collect GI tracts from fish destined for human consumption\nC_LI

ecology↗