Chronic Stress Modulates Interneuronal Plasticity: Effects on PSA-NCAM and Perineuronal Nets in Cortical and Extracortical Regions
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Chronic stress has an important impact on the adult brain. However, most of the knowledge on its effects is focused on principal neurons and less on inhibitory neurons. Consequently, recent reports have begun to describe stress-induced alterations in the structure, connectivity and neurochemistry of interneurons. Some of these changes appear to be mediated by certain molecules particularly associated to interneurons, such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) and components of the perineuronal nets (PNN), specialized regions of the extracellular matrix. These plasticity-related molecules modulate interneuronal structure and connectivity, particularly of parvalbumin expressing basket interneurons, both during development and adult life. These inhibitory neurons are specially affected after chronic stress and in some stress-related disorders, in which the expression of PSA-NCAM and certain components of PNN are also altered. For these reasons we have decided to study PSA-NCAM, PNN and parvalbumin expressing interneurons after 10 days of chronic restraint stress, a time point in which its behavioral consequences are starting to appear. We have focused initially on the medial prefrontal cortex (mPFC), basolateral amygdala (BLA) and hippocampus, regions affected by stress and stress-related psychiatric diseases, but we have also explored the habenula and the thalamic reticular nucleus (TRN) due to the important presence of PNN and their relationship with certain disorders. PSA-NCAM expression was increased by stress in the stratum lacunosum-moleculare of CA1. Increases in parvalbumin immunoreactive cells were detected in the mPFC and the BLA, but were not accompanied by increases in the number of parvalbumin expressing perisomatic puncta on the somata of principal neurons. The number of PNN was also increased in the mPFC and the habenula, although habenular PNN were not associated to parvalbumin cells. Increased expression of parvalbumin and components of PNN were also detected in the TRN after chronic restraint stress, revealing for the first time substantial effects on this region. Our study shows that, even a short chronic stress protocol, can induce consistent changes in interneuronal plasticity-related molecules in cortical and extracortical regions, which may represent initial responses of inhibitory circuits to counteract the effects of this aversive experience.
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Chronic stress increases PNN numbers in the mPFC and habenula.
“For example, chronic stress increases PNN numbers in the mPFC and habenula [150].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [150]
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Alterations of perineuronal nets in the dorsolateral prefrontal cortex of neuropsychiatric patients
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Self-citationHow Stress Influences the Dynamic Plasticity of the Brain’s Extracellular Matrix
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Perineuronal Nets: Subtle Structures with Large Implications
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Self-citationEarly life stress and brain plasticity: from molecular alterations to aberrant memory and behavior
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Implications of Extended Inhibitory Neuron Development
Kim, J.-Y., & Paredes, M. F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105113 · Cited by 35 · see citing works
“Recent studies have reported that PSA-NCAM, which is typically viewed as an anti-adhesion molecule that interacts with the ECM and promotes neuronal migration, can also affect synaptic dynamics and regulate the plasticity of PV+ interneurons in the medial PFC under chronic stress [147] and structural plasticity in the…”
BackgroundFrom molecules to behavior: Implications for perineuronal net remodeling in learning and memory
Sanchez, B., Kraszewski, P., Lee, S., & Cope, E. C. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.16036 · Cited by 37 · see citing works
“In response to chronic restraint stress, PNN coverage increases in the medial prefrontal cortex and thalamus, but PNN density decreases in the hippocampus (Pesarico et al., 2019 ).”
Stress, associative learning, and decision-making
Giovanniello, J. R., Bravo-Rivera, C., Rosenkranz, J. A., & Lattal, K. M. (2023) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2023.107812 · Cited by 38 · see citing works
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Impact of stress on inhibitory neuronal circuits, our tribute to Bruce McEwen
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“Conversely, PNNs density was reduced in hippocampal CA1 region after 10 days of chronic restraint stress protocol, but increased in the mPFC (Pesarico et al., 2019).”
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Extrasynaptic therapeutic targets in substance use and stress disorders
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Clozapine increased c-Fos protein expression in several brain subregions of socially isolated rats
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Modulation of stress-, pain-, and alcohol-related behaviors by perineuronal nets
Aguilar, J. S., & Lasek, A. W. (2024) · Neurobiology of Stress · doi:10.1016/j.ynstr.2024.100692 · Cited by 10 · see citing works
“…to chronic variable stress had increased PNN numbers throughout the cortex (Simard et al., 2018) and similarly, male rats exposed to chronic restraint stress had increased PNN numbers in the medial PFC, which included the infralimbic, prelimbic, and cingulate regions (Pesarico et al., 2019).”
Golgi satellites are essential for polysialylation of NCAM and expression of LTP at distal synapses.
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“The BLA contains mostly glutamatergic pyramidal neurons, which mainly project to the central amygdala (CeA) and to multiple extraamygdaloid regions (Pitkänen et al., 2000).”
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“Chronic restraint stress for 10 days induces long-term alterations in cortical interneuron plasticity, involving key molecular players such as the polysialylated form of neural cell adhesion molecule (PSA-NCAM) and perineuronal nets (PNN) [29].”
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“In the study by Pesarico et al. (2019), restraint stress led to increased PNN numbers in the habenula and PFC, two regions critical for emotional processes, with no observed change in the BLA and a decrease in the HIP.”
BackgroundMethodSARS-CoV-2 Attacks in the Brain: Focus on the Sialome
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Unveiling the enigma of anxiety disorders and depression: from pathogenesis to treatment
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“Similarly, a 10-day CRS or a 6-day inescapable foot shock regimen increases PNN density in the hippocampal CA1 region (Fan et al., 2024; Pesarico et al., 2019), and enhances both the frequency and amplitude of mIPSCs (Li et al., 2023c).”
Perineuronal nets: Cruise from a honeycomb to the safety nets
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Long term effects of peripubertal stress on the thalamic reticular nucleus of female and male mice
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Nociceptive sensitivity under stress influence
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Parvalbumin interneurons under stress: converging mechanisms of vulnerability
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“105 This change is accompanied by increased PV-positive cell counts in the medial PFC and BLA, as well as enhanced PNN density in the medial PFC. 105 Similarly, in the social defeat stress model, cognitive impairments coincide with dysregulation of PVIs and PNNs in the HIP.”
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“In some cases, these changes can lead to a reduction in PNN density (Pesarico et al., 2019).”
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“…role of PNNs in restricting plasticity associated with learning and that PNN maturation is influenced by physiological stimuli, such as stress (Pesarico et al., 2019), CS-induced activity of the MHb may thus modify PNN structures leading to increased or decreased stress-response of the HIPOPS…”
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“Although stress have been shown to modulate these molecules (Sandi, 2004; Bisaz et al., 2009; Pesarico et al., 2019), as no differences were observed between context-exposed and pseudo-trained groups, the observed expression changes cannot be attributed to context nor to the stress that may accompany eyelid electric s…”
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“In another study, J. Nacher and his team demonstrated that in prefrontal cortical and limbic regions, chronic restraint stress (10 days) modulates PSA-NCAM expression and perineu-ronal nets, affecting interneuronal plasticity [108].”
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“Our data in adult rats align with reports that repeated restraint does not alter PV+ PNNs number in the adult mPFC (Pesarico et al. 2019).”
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Self-citation
- Authors
- Pesarico, A. P., Bueno-Fernandez, C., Guirado, R., Gómez-Climent, M. Á., Curto, Y., Carceller, H., & Nacher, J.
- Affiliations
- Universitat de València (ES)
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2019-05-07
- Volume
- 13
- Pages
- 197-197
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC6524695
- OpenAlex
- W2944631368
- Cited by
- 62
- References
- 67
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 8 · 2023: 9 · 2022: 11 · 2021: 6 · 2020: 12 · 2019: 4
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Re-Unir (International University of La Rioja) (submittedVersion, other-oa)
- Repository of Digital Objects for Teaching Research and Culture (University of Valencia) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- Funders
- Ministerio de Economía, Industria y Competitividad, Gobierno de España
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- chronic stress, restraint stress, interneurons, PSA-NCAM, perineuronal nets, parvalbumin, medial prefrontal cortex, basolateral amygdala, hippocampus, habenula, thalamic reticular nucleus, extracellular matrix, inhibitory circuits, stress-related psychiatric disorders
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