Hypothalamic Perineuronal Nets Are Regulated by Sex and Dietary Interventions

Abstract

Perineuronal nets (PNNs) are widely present in the hypothalamus, and are thought to provide physical protection and ion buffering for neurons and regulate their synaptic plasticity and intracellular signaling. Recent evidence indicates that PNNs in the mediobasal hypothalamus play an important role in the regulation of glucose homeostasis. However, whether and how hypothalamic PNNs are regulated are not fully understood. In the present study, we examined whether PNNs in various hypothalamic regions in mice can be regulated by sex, gonadal hormones, dietary interventions, or their interactions. We demonstrated that gonadal hormones are required to maintain normal PNNs in the arcuate nucleus of hypothalamus in both male and female mice. In addition, PNNs in the terete hypothalamic nucleus display a sexual dimorphism with females higher than males, and high-fat diet feeding increases terete PNNs only in female mice but not in male mice. On the other hand, PNNs in other hypothalamic regions are not influenced by sex, gonadal hormones or dietary interventions. In summary, we demonstrated that hypothalamic PNNs are regulated in a region-specific manner and these results provide a framework to further investigate the potential functions of PNNs in regulating energy/glucose homeostasis at the interplay of sex, gonadal hormones and diets.

Perineuronal nets in the rat medial prefrontal cortex alter hippocampal-prefrontal oscillations and reshape cocaine self-administration memories

“…An additional limitation is that we used only male rats. Acquisition and reinstatement in cocaine self-administering rats is higher in females 122, 123 , and our group and others have reported sex differences in PNN intensity in reward-associated brain regions 124–128 . It is therefore possible that ABC would impact males and females differently, and future studies would also need to take into account the estrous phase 129, 130 .…”

“…An additional limitation is that we used only male rats. Acquisition and reinstatement in cocaine self-administering rats is higher in females 122,123 , and our group and others have reported sex differences in PNN intensity in reward-associated brain regions [124][125][126][127][128] . It is (which was not certified by peer review) is the author/funder.…”

Microbiome depletion prior to repeat mild TBI differentially alters social deficits and prefrontal cortex plasticity in adolescent and adult rats

“…To ensure consistency and ensure counts of PNNs and not “loose” fragments of extracellular matrix structures, only PNNs that were complete and not degraded were counted. 96 Colocalised cells were counted using the same program.…”

Enhanced expression of parvalbumin and perineuronal nets in the medial prefrontal cortex after extended‐access cocaine self‐administration in rats

“…Acquisition and reinstatement in cocaine selfadministering rats has been reported to be higher in females, 68,69 and our group as well as others have reported sex differences in PNN intensity in reward-associated brain regions. [70][71][72][73][74] Thus, we might expect a greater impact of cocaine self-administration in female versus male rats, but future studies would also need to take into account the estrous phase.…”