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Biology subjects

Chang, V. N.

Publications and source records attributed to Chang, V. N..

2 recordsLinked to original sources

Consumption of clinically relevant cannabidiol doses during pregnancy alters postnatal behavior in offspring

Pregnant people use cannabidiol (CBD), a non-psychoactive cannabinoid of cannabis, due to its perceived safety and to treat side-effects such as nausea, insomnia, pain, and anxiety. However, CBD crosses the placenta and accumulates in the fetal brain, where it can activate or repress the function of several molecular targets that are important for brain development. While consumption of high doses of CBD during pregnancy have been shown to disrupt offspring neurodevelopment and postnatal behavior, lower, more clinically relevant doses have not been assessed. Here, we show that oral consumption of 10 mg/kg/day CBD during pregnancy increases thermal pain sensitivity in exposed male mouse offspring. Additionally, we find that the same dose impairs cognition and reduces excitability of the prefrontal cortex in exposed female mouse offspring. These data show that lower doses of CBD consumption during pregnancy can impair fetal brain development and postnatal behavior.

pharmacology and toxicology↗

Endogenous recovery of hippocampal function following global cerebral ischemia in juvenile female mice is influenced by neuroinflammation and circulating sex hormones.

Cardiac arrest-induced global cerebral ischemia (GCI) in childhood often results in learning and memory deficits. We previously demonstrated in a murine cardiac arrest and cardiopulmonary resuscitation (CA/CPR) mouse model that a cellular mechanism of learning and memory, long-term potentiation (LTP), is acutely impaired in the hippocampus of juvenile males, correlating with deficits in memory tasks. However, little is known regarding plasticity impairments in juvenile females. We performed CA/CPR in juvenile (P21-25) female mice and used slice electrophysiology and hippocampal dependent behavior to assess hippocampal function. LTP was and contextual fear were impaired 7-days after GCI and endogenously recovered by 30-days. LTP remained impaired at 30 days in ovariectomized females, suggesting the surge in gonadal sex hormones during puberty mediates endogenous recovery. Unlike juvenile males, recovery of LTP in juvenile females was not associated with BDNF expression. NanoString transcriptional analysis revealed a potential role of neuroinflammatory processes, and specifically Cd68 pathways, in LTP impairment and hormone-dependent recovery. We were able to restore LTP in ovariectomized females with chronic and acute PPT administration, implicating estrogen receptor alpha in recovery mechanisms. This study supports a mechanism of endogenous LTP recovery after GCI in juvenile female mice which differs mechanistically from juvenile males and does not occur in adults of either sex.

neuroscience↗