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Although epilepsy is one of the most common chronic neurological disorders with a prevalence of approximately 1.0 %, the underlying pathophysiology remains to be elucidated. Understanding the molecular and cellular mechanisms involved in the development of epilepsy is important for the development of appropriate therapeutic strategy. In this study, we investigated the effects of status epilepticus on astrocytes, microglia, and extracellular matrix (ECM) molecules in the somatosensory cortex and piriform cortex of mice. Activation of astrocytes was observed in many cortices except the retrosplenial granular cortex after pentylenetetrazol (PTZ)-induced kindling in mice. Activated astrocytes in the cortex were found in layers 1-3 but not in layers 4-6. In the somatosensory and piriform cortices, no change was observed in the number of parvalbumin (PV)-positive neurons and PV-positive neurons covered with perineuronal nets. However, the amount of ECM in the extracellular space increased. The expression of VGLUT1- and GAD67-positive synapses also increased. Thus, in the PTZ-kindling epilepsy mice model, an increase in the number of ECM molecules and activation of astrocytes were observed in the somatosensory cortex and piriform cortex. These results indicate that PTZ-induced seizures affect not only the hippocampus but also other cortical areas. Our study findings may help to develop new therapeutic approaches to prevent seizures or their sequelae., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aging is associated with decline in cognitive function, but the underlying mechanisms have not been elucidated. Normal activity of pyramidal cells and parvalbumin-expressing interneurons (PV neurons) is essential for cognitive function. PV neurons participate in the regulation of pyramidal-cell firing. Abnormal function of PV neurons may occur with aging. We analyzed the density and the percentage of PV neurons surrounded by perineuronal nets (PNNs) in the entire cortex of adult (3-month-old) and aged (24-month-old) mice. PNNs are extracellular matrix molecules that cover PV neurons and control synaptic plasticity. PV-neuron density decreased in some cortical areas of aged compared to adult mice. In particular, in the retrosplenial granular cortex (RSG) of aged mice, pyramidal cells expressed PV protein at high levels. This study suggests that the RSG of aged mice is in an abnormal activated state. RSG function abnormality may be part of the cognitive decline mechanism., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cognitive function declines with age. Such function depends on γ-oscillation in the frontal cortex. Pyramidal neurons, and the parvalbumin-expressing interneurons (PV neurons) that control them, are important for the generation of γ-oscillation. The mechanism by which cognitive function declines is unclear. Perineuronal nets (PNNs) mainly surround the soma and proximal dendrites and axon segments of PV neurons in the cerebral cortex. Previous evidence indicates that PNNs inhibit neural plasticity. If this is true, an increase in the number of neurons surrounded by PNNs or in the thickness or density of the PNNs around neurons could decrease plasticity in the cortex. To determine if an aging-related change in cortical PNNs occurs, we examined the influence of aging on PV neurons and whether Wisteria floribunda agglutinin-positive PNNs differ depending on the cortical area. The results showed that the number of PV neurons/mm 2 did not change in many areas of the cortex as mice aged. In contrast, the number of neurons in the sensory cortex surrounded by PNNs increased as mice aged. Thus, with age, PNN density increases in some cortical areas but not in others. In addition, the expression level of PV protein in PV neurons decreased with aging in the whole cortex. We suggest that decreased expression of PV protein impairs fast spiking in PV neurons. We propose that PNNs surround more neurons as age increases. This aging-related increase in PNNs decreases plasticity in the cerebral cortex and reduces cognitive function. The first step in investigating this proposal would be to determine if PNN density increases with age., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Ionizing irradiation has several long-term effects including progressive cognitive impairment. Cognitive deterioration generally appears to be caused by abnormalities in the hippocampal dentate gyrus, with abnormal function of parvalbumin-expressing interneurons (PV neurons) in the cerebral cortex. PV neurons are vulnerable to oxidative stress, which can be caused by ionizing irradiation. We speculated that selective impairment of specific brain regions due to ionizing irradiation may alter the degree of cognitive impairment. Methods: We irradiated mature mouse brains with 20 Gy-ionizing irradiation. Subsequently, we analyzed behavioral abnormalities and changes in the number of PV neurons. Results: PV neuron density was significantly lower in some cortical regions of irradiated mice than in control mice. Within 1 week of irradiation, both body weight and temperature of irradiated mice decreased. In the forced swim test, irradiated mice spent significantly less time immobile than did control mice. However, irradiated mice did not display any abnormalities in the elevated plus maze test, Y-maze test, tail suspension test, and social interaction test between 3 to 6 days after irradiation. Conclusions: These results suggest that high-dose irradiation is less likely to cause brain dysfunction in the subacute phase. Moreover, the vulnerability of PV neurons appears to be brain-region specific. [ABSTRACT FROM AUTHOR]

Abstract In the central nervous system (CNS), extracellular matrix (ECM) molecules comprise more than 20% of the volume and are involved in neuronal plasticity, synaptic transmission, and differentiation. Perineuronal nets (PNNs) are ECM molecules that highly accumulate around the soma of neurons. The components of the ECM in the CNS include proteins, proteoglycans, and glycosaminoglycans. Although hyaluronic acid (HA) is considered a constituent element of PNNs, the distribution of HA in the cortex has not been clarified. To elucidate the cortical region-specific distribution of HA, we quantitatively analyzed HA binding protein (HABP)-positive PNNs in the mature mouse cerebral cortex. Our findings revealed that HABP-positive PNNs are present throughout the mouse cortex. The distribution of many HABP-positive PNNs differed from that of Wisteria floribunda agglutinin-positive PNNs. Furthermore, we observed granular-like HABP-positive PNNs in layer 1 of the cortex. These findings indicate that PNNs in the mouse cortex show region-dependent differences in composition. HABP-positive PNNs in layer 1 of the cortex may have different functions such as neuronal differentiation, proliferation, and migration unlike what has been reported for PNNs so far. [ABSTRACT FROM AUTHOR]