Age-dependent and region-specific alteration of parvalbumin neurons, perineuronal nets and microglia in the mouse prefrontal cortex and hippocampus following obesogenic diet consumption

Amy C Reichelt,Lisa M Saksida,Claire A Lemieux,Ashmita Singh,Oren Princz-Lebel,Timothy J Bussey

doi:10.1038/s41598-021-85092-x

Abstract

Emergent evidence demonstrates that excessive consumption of high fat and high sugar (HFHS) diets has negative consequences on hippocampal and prefrontal cortex (PFC) function. Moreover, the delayed maturation of the PFC including the late development of parvalbumin-expressing (PV) interneurons and perineuronal nets (PNNs) may promote vulnerability to HFHS diet-induced nutritional stress. However, the young brain may have some resistance to diet-induced neuroinflammation. Thus, we examined the impact of a HFHS diet commencing either in adolescence or adulthood in male mice. PV interneurons, PNNs and microglia were assessed using immunohistochemistry. We observed greater numbers of PV neurons and PNNs in the hippocampus and the prelimbic and infralimbic PFC in adult mice in comparison to our younger cohort. Mice that consumed HFHS diet as adults had reduced numbers of hippocampal PV neurons and PNNs, which correlated with adiposity. However, we saw no effects of diet on PV and PNNs in the PFC. HFHS diet increased microgliosis in the adult cohort, and morphological changes to microglia were observed in the PFC and hippocampus of the adolescent cohort, with a shift to activated microglia phenotypes. Taken together, these findings demonstrate different regional and age-specific effects of obesogenic diets on PV neurons, PNNs and microglia.

Highlights

Emergent evidence demonstrates that excessive consumption of high fat and high sugar (HFHS) diets has negative consequences on hippocampal and prefrontal cortex (PFC) function
The HFHS diet increased adiposity measured by retroperitoneal and gonadal white adipose tissue mass (WAT, Fig. 1D, main effect diet F(1,28) = 71.65, p < 0.0001) and liver weights (Fig. 1E, main effect diet F(1,28) = 13.84, p < 0.001)
We found a significant correlation between ionized calcium binding adaptor molecule-1 (IBA-1) fluorescence and PV neuron counts in the PrL in the adults but not adolescent cohort (Fig. S5A adolescent p = 0.498, adult p = 0.048), no further significant correlations were seen in the IL (Fig. S5B adolescent p = 0.180, adult p = 0.414) and orbitofrontal cortex (OFC) (Fig. S5C adolescent p = 0.408, adult p = 0.147)

Summary

Introduction

Emergent evidence demonstrates that excessive consumption of high fat and high sugar (HFHS) diets has negative consequences on hippocampal and prefrontal cortex (PFC) function. HFHS diet increased microgliosis in the adult cohort, and morphological changes to microglia were observed in the PFC and hippocampus of the adolescent cohort, with a shift to activated microglia phenotypes Taken together, these findings demonstrate different regional and age-specific effects of obesogenic diets on PV neurons, PNNs and microglia. Due to the relatively late development of PV neurons in the PFC17,22, environmental challenges during early life such as stress or poor nutrition may have pronounced and enduring effects on these neurons that could precipitate the development of neuropsychiatric c onditions[29] Another maturational event is the development of specialized extracellular matrix structures called perineuronal nets (PNNs), which frequently surround cortical PV neurons[30]. The prolonged maturation of PNNs has been noted within the frontal cortices[17] and the hippocampus[39 ], PV neurons in the adolescent brain may be more vulnerable to obesity-evoked alterations to the extracellular environment as PNNs have not fully formed their protective microenvironments[26,27,40,41]

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