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

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.

Neurogenesis mediated plasticity is associated with reduced neuronal activity in CA1 during context fear memory retrieval

“…As expected, we observed a significant age-dependent decrease in neurogenesis and a corresponding agedependent increase in PNNs in CA1 (Fig. 4c,d) 41 . These results provide further supporting evidence that the levels of adult neurogenesis in the dentate gyrus impact CA1 PNN expression.…”

Microglia as hackers of the matrix: sculpting synapses and the extracellular space

“…The loss of protective PNNs leaves PV + and other enwrapped neurons susceptible to injury [92,156,157], and accordingly, we found that PNN reductions preceded decreases in PV + neurons in AD [90], where PV + cells are particularly relevant to disease [197][198][199][200]. Indeed, PNN loss is associated with neuronal death and/or degeneration in a number of disease contexts [160,169,176,180,190,193,201]. It should be noted that several studies failed to detect differences in PNN abundance in clinical AD [202][203][204][205], and this may be partly attributable to the brain region under investigation or the method of PNN labeling used.…”

“…PNN deficits/decreases have also been observed across more diverse diseases, many if not all of which are also generally associated with microglial activation, including multiple sclerosis [169], stroke [180][181][182][183][184], traumatic brain injury [185,186], spinal cord injury [187], epilepsy [188,189], obesogenic high fat and high sugar diet consumption [190], glioma [160], Alzheimer's disease [90,[191][192][193], and schizophrenia [167,[194][195][196]. The loss of protective PNNs leaves PV + and other enwrapped neurons susceptible to injury [92,156,157], and accordingly, we found that PNN reductions preceded decreases in PV + neurons in AD [90], where PV + cells are particularly relevant to disease [197][198][199][200].…”

Impact of Perineuronal Nets on Electrophysiology of Parvalbumin Interneurons, Principal Neurons, and Brain Oscillations: A Review

“…Exercise also alters PNNs, and the effects are dependent on the brain region examined (Smith et al, 2015 ; Briones et al, 2021 ). Several studies have shown that environmental enrichment either during early life (Carstens et al, 2016 ; Stamenkovic et al, 2017 ; O’Connor et al, 2019 ) or adulthood (Foscarin et al, 2011 ; Slaker et al, 2016 ) alters PNNs, as does a high-fat diet during adolescence (Reichelt et al, 2019 , 2021 ) and adulthood (Dingess et al, 2018 , 2020 ). Two studies have shown circadian/diurnal changes, with higher numbers or intensity of PNNs in the dark phase in rodents (Pantazopoulos et al, 2020 ; Harkness et al, 2021 ).…”