Influences of age and pubertal status on number and intensity of perineuronal nets in the rat medial prefrontal cortex

Drzewiecki, Carly M.; Willing, Jari; Juraska, Janice M.

doi:10.1007/s00429-020-02137-z

Cited by 44 publications

(48 citation statements)

References 97 publications

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“…Early life is rife with sensitive periods during which aberrant experience can have lasting effects on plasticity and behavioral development ( Bicks et al, 2020 ; Chocyk et al, 2010 ). Heightened neural malleability during early stages of development may – in part – stem from protracted formation of PNNs ( Gildawie et al, 2020a ; Mauney et al, 2013 ), and may also depend on sex and pubertal status ( Drzewiecki et al, 2020 ). Here, we show a clear sex-specific effect of multiple hits of early life adversity during distinct windows of susceptibility, where females demonstrate a potentiated decrease in PV number and PNN structural integrity following neonatal MS and juvenile SI.…”

Section: Resultsmentioning

confidence: 99%

A two-hit adversity model in developing rats reveals sex-specific impacts on prefrontal cortex structure and behavior

Gildawie

Ryll

Hexter

et al. 2021

Developmental Cognitive Neuroscience

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Adversity early in life substantially impacts prefrontal cortex (PFC) development and vulnerability to later-life psychopathology. Importantly, repeated adverse experiences throughout childhood increase the risk for PFC-mediated behavioral deficits more commonly in women. Evidence from animal models points to effects of adversity on later-life neural and behavioral dysfunction; however, few studies have investigated the neurobiological underpinnings of sex-specific, long-term consequences of multiple developmental stressors. We modeled early life adversity in rats via maternal separation (postnatal day (P)2-20) and juvenile social isolation (P21-35). In adulthood, anxiety-like behavior was assessed in the elevated zero maze and the presence and structural integrity of PFC perineuronal nets (PNNs) enwrapping parvalbumin (PV)-expressing interneurons was quantified. PNNs are extracellular matrix structures formed during critical periods in postnatal development that play a key role in the plasticity of PV cells. We observed a female-specific effect of adversity on hyperactivity and risk-assessment behavior. Moreover, females – but not males – exposed to multiple hits of adversity demonstrated a reduction in PFC PV cells in adulthood. We also observed a sex-specific, potentiated reduction in PV + PNN structural integrity. These findings suggest a sex-specific impact of repeated adversity on neurostructural development and implicate PNNs as a contributor to associated behavioral dysfunction.

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Section: Resultsmentioning

confidence: 99%

A two-hit adversity model in developing rats reveals sex-specific impacts on prefrontal cortex structure and behavior

Gildawie

Ryll

Hexter

et al. 2021

Developmental Cognitive Neuroscience

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show abstract

“…Heightened neural malleability during early stages of development may -in part -stem from protracted formation of PNNs Mauney et al, 2013), and may also depend on sex and pubertal status (Drzewiecki et al, 2020). Here, we show a clear sex-specific effect of multiple hits of early life adversity during distinct windows of susceptibility, where females demonstrate a potentiated decrease in PV number and PNN structural integrity following neonatal MS and juvenile SI.…”

Section: Resultsmentioning

confidence: 63%

A two-hit adversity model in developing rats reveals sex-specific impacts on prefrontal cortex structure and behavior

Gildawie

Ryll

Hexter

et al. 2020

Preprint

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Adversity early in life substantially impacts prefrontal cortex (PFC) development and vulnerability to later-life psychopathology. Importantly, repeated adverse experiences throughout childhood increase the risk for PFC-mediated behavioral deficits more commonly in women. Evidence from animal models points to effects of adversity on later-life neural and behavioral dysfunction; however, few studies have investigated the neurobiological underpinnings of sex-specific, long term consequences of multiple developmental stressors. We modeled early life adversity in rats via maternal separation (postnatal day (P)2-20) and juvenile social isolation (P21-35). Adult (P85) male and female rats were assessed for differences in the presence and structural integrity of PFC perineuronal nets (PNNs) enwrapping parvalbumin (PV)-expressing interneurons. PNNs are extracellular matrix structures formed during critical periods in postnatal development that play a key role in the plasticity of PV cells. Females - but not males - exposed to multiple hits of adversity demonstrated a reduction in PFC PV cells in adulthood. We also observed a sex-specific, potentiated reduction in PV+ PNN structural integrity. Moreover, correlations between neural disruption and hyperactivity/risk-assessment behavior were altered by adversity differently in males and females. These findings suggest a sex-specific impact of repeated adversity on neurostructural development and implicate PNNs as a contributor to associated behavioral dysfunction.

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“…Neurons and pyknotic cells within the mPFC were counted using similar methods to those previously described by our laboratory ( Drzewiecki et al, 2020 , Kougias et al, 2018 , Willing and Juraska, 2015 ) using the StereoInvestigator optical disector, which allows for unbiased stereology. In the mature mPFC, the dorsal border is distinguished by a thinning layer I and increased cell density in layer III while the ventral is marked by a blurring of lamina borders.…”

Section: Methodsmentioning

confidence: 99%

Cell death in the male and female rat medial prefrontal cortex during early postnatal development

Sellinger

Drzewiecki²,

Willing³

et al. 2021

IBRO Neuroscience Reports

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Apoptosis, programmed cell death, is a critical component of neurodevelopment occurring in temporal, spatial, and at times, sex-specific, patterns across the cortex during the early postnatal period. During this time, the brain is particularly susceptible to environmental influences that are often used in animal models of neurodevelopmental disorders. In the present study, the timing of peak cell death was assessed by the presence of pyknotic cells in the male and female rat medial prefrontal cortex (mPFC), a cortical region that in humans, is often involved in developmental disorders. One male and one female rat per litter were sacrificed at the following ages: postnatal day (P)2, 4, 6, 8, 10, 12, 14, 16, 18, and 25. The mPFC was Nissl-stained, the densities of pyknotic cells and live neurons were stereologically collected, and the number of pyknotic cells per 100 live neurons, pyknotic cell density, and neuron density were analyzed. Males and females showed a significant peak in the ratio of pyknotic to live neurons on P8, and in females, this elevation persisted through P12. Likewise, the density of pyknotic cells peaked on P8 in both sexes and persisted through P12 in females. The timing of cell death within the rat mPFC will inform study design in experiments that employ early environmental manipulations that might disrupt this process.

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Influences of age and pubertal status on number and intensity of perineuronal nets in the rat medial prefrontal cortex

Cited by 44 publications

References 97 publications

A two-hit adversity model in developing rats reveals sex-specific impacts on prefrontal cortex structure and behavior

A two-hit adversity model in developing rats reveals sex-specific impacts on prefrontal cortex structure and behavior

A two-hit adversity model in developing rats reveals sex-specific impacts on prefrontal cortex structure and behavior

Cell death in the male and female rat medial prefrontal cortex during early postnatal development

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