Biology subjects

Giacometti, L. L.

Publications and source records attributed to Giacometti, L. L..

4 recordsLinked to original sources

bioRxiv2026

CA inhibitor 1 treatment has only transient effects on estrous cyclicity in mice

Approximately 45% of new HIV infections worldwide occur in women and girls and adherence to pre-exposure prophylaxis (PrEP) to prevent HIV infection is limited. Long-acting PrEP such as lenacapavir may improve adherence. One barrier to PrEP usage in women and girls is impact on the menstrual cycle, though impacts of long-acting PrEP are unclear. To model the effect of lenacapavir administration on cyclicity, adult female C57Bl/6J mice were injected with CA inhibitor 1 and assessed for estrous cyclicity. Ca inhibitor 1 transiently delayed the start of the next cycle. However, Ca inhibitor 1 was associated with a higher proportion of normal length estrous cycles. Ca inhibitor 1 did not impact astrocyte immunoreactivity or chronic cellular activity in the medial preoptic area (mPOA), a major regulator of the estrous cycle. These findings suggest that lenacapavir may be a viable PrEP alternative for those concerned with PrEP impacts on menstrual cycle.

neuroscience↗

bioRxiv2025

Depression-like behavior following mild traumatic brain injury in adolescent rats: a role for limbic neuropeptides

Mild traumatic brain injury (mTBI) is common among adolescents because of their participation in contact sports and mTBI is more likely to lead to depression-related behaviors in girls than boys. Various neuropeptides, often within the limbic system, have been implicated in the regulation of depression-related behaviors. To identify potential neuropeptide involvement in behavioral effects of mTBI, this study used adolescent-age male and female rats to compare the effects of single and repetitive mTBI on depression-like behavior and limbic neuropeptide expression. Female but not male rats displayed increased immobility in the forced swim test compared to sham-injured rats at 5-weeks (chronic), but not 2-weeks (acute) following closed-head injury, and this effect was estrous cycle-dependent following single but not repetitive injury. In the nucleus accumbens (NAc), a major limbic nucleus, mRNA expression of corticotropin-releasing factor (CRF) and dynorphin (DYN) was decreased after single injury only in female rats, particularly during the estrus phase, while expression of enkephalin (ENK) was decreased after repetitive injury. In the paraventricular nucleus of the thalamus (PVT), another limbic nucleus, mRNA expression of pituitary adenylate cyclase-activating polypeptide (PACAP) was increased in repetitively injured female but not male rats at 2- and 5-weeks but was unchanged in single injured female rats compared to sham-injured rats. These data suggest that depression-like behavior emerges in the chronic phase following adolescent mTBI only in females, being estrous cycle-dependent following single-injury. Moreover, reduced ENK in the NAc and elevated PACAP in the PVT may contribute to depression-like behavior in females following repetitive mTBI.

neuroscience↗

bioRxiv2025

Subcellular interactions of neuropeptide Y and corticotropin-releasing factor in the central nucleus of the amygdala in the mouse

Neuropeptide Y (NPY) is ubiquitously distributed throughout the central nervous system. Recognized as a mediator of stress resilience, NPY has been shown to counteract the excitatory effects of the neuropeptide corticotropin-releasing factor (CRF), that orchestrates the stress response. In the mouse, while NPY and CRF exhibit a high degree of neuroanatomical association in the central nucleus of the amygdala (CeA) indicating potential significant interactions, the synaptic organizations of these neuropeptides have not been elucidated. In the present study, we determined the interactions between NPY and CRF in the CeA. Immunofluorescence microscopy presented that NPY-immunoreactive varicose processes were distributed throughout the CeA and contacted CRF-containing neurons. Using electron microscopy, immunoperoxidase labeling for NPY and gold-silver labeling for CRF showed that NPY-labeled axon terminals (NPY-t) form synapses with CRF-labeled dendrites (CRF-d). Semi-quantitative analysis revealed that 163 of NPY-t directly target CRF-d. In addition, approximately 85% of NPY-t form symmetric synapses with CRF-d while approximately 1% form asymmetric synapses. These findings provide the first ultrastructural evidence that NPY-containing axon terminals make direct contact with CRF-containing dendrites in the CeA. This suggests that the CRF-containing neurons in the CeA may be a key site for NPY action, potentially influencing brain regions involved in stress responses and stress-related psychiatric disorders, and alcohol use disorders.

neuroscience↗

bioRxiv2023

Impaired extinction of cocaine seeking in HIV-infected mice is accompanied by peripheral and central immune dysregulation

Substance use disorders (SUDs) are highly comorbid with HIV infection, necessitating an understanding of the interactive effects of drug exposure and HIV. The relationship between progressive HIV infection and cocaine use disorder is likely bidirectional, with cocaine use having direct effects on immune function while HIV infection can alter addiction-related behavior. To better characterized the neurobehavioral and immune consequences of HIV infection and cocaine exposure, this study utilized a humanized mouse model to investigate the outcomes of progressive HIV infection on cocaine-related behaviors in a cocaine conditioned place preference (CPP) model, and the interactive effects of cocaine and HIV infection on peripheral and central nervous system inflammation. HIV infection did not impact the formation of a cocaine CPP, but did result in resistance to extinction of the CPP. No effects of HIV on yohimbine-primed reinstatement or cocaine seeking under conflict were observed. These behavioral alterations were accompanied by immune changes in HIV infected mice, including increased prefrontal cortex astrocyte immunoreactivity and brain-region specific effects on microglia number and reactivity. Peripheral immune system changes were observed in both mouse and human markers. Among other targets, this included HIV-induced reductions in mouse IL-1 and G-CSF and human TNF and cocaine-induced alterations in human TNF and mouse GM-CSF such that cocaine exposure increases both cytokines only in the absence of HIV infection. Together these data provide new insights into the unique neurobehavioral processes underlying HIV infection and cocaine use disorders, and further how they interact to effect immune responses.

neuroscience↗