Three Types of Demyelination, Perivenous, Confluent, and Perineuronal Nets-Rich in a COVID-19 Patient With Meningoencephalomyelitis.

Neurologic symptoms are common in COVID-19, and a variety of neuropathological changes have been reported. One of the important neuropathological findings is demyelination. However, the underlying pathogenesis of demyelination remained poorly understood. We witnessed a case of COVID-19 with distinct types of demyelination in the cerebrum, medulla oblongata, and spinal canal, who died of sepsis. The postmortem examination showed the solitary massive demyelination in the medulla oblongata. The massive lesion was filled with components of perineuronal nets. In the spinal canal, confluent demyelination in bilateral lateral and dorsal funiculi was detected over the entire length from C1 to S5, which was maximum at the level of cervical spinal canal stenosis. Demyelination in the cerebrum was mainly perivenular, and augmented in the area of lacunar infarcts and dilated perivascular spaces. Considering the distribution patterns of the following three types of demyelination, the traces of viral spreading could be highlighted. Discontinuous perivenous demyelination in the cerebrum showed the result of hematogenous spreading. Longitudinal confluent demyelination of the spinal cord should be the picturesque of the trace of axonal spreading. The distribution of demyelination was possibly modified by the underlying diseases, diabetes mellitus, hypertension, and spinal canal stenosis.

Addiction and the cerebellum with a focus on actions of opioid receptors.

Increasing evidence suggests that the cerebellum could play a role in the higher cognitive processes involved in addiction as the cerebellum contains anatomical and functional pathways to circuitry controlling motivation and saliency. In addition, the cerebellum exhibits a widespread presence of receptors, including opioid receptors which are known to play a prominent role in synaptic and circuit mechanisms of plasticity associated with drug use and development of addiction to opioids and other drugs of abuse. Further, the presence of perineural nets (PNNs) in the cerebellum which contain proteins known to alter synaptic plasticity could contribute to addiction. The role the cerebellum plays in processes of addiction is likely complex, and could depend on the particular drug of abuse, the pattern of use, and the stage of the user within the addiction cycle. In this review, we discuss functional and structural modifications shown to be produced in the cerebellum by opioids that exhibit dependency-inducing properties which provide support for the conclusion that the cerebellum plays a role in addiction.

p75 Neurotrophin Receptor Activation Regulates the Timing of the Maturation of Cortical Parvalbumin Interneuron Connectivity and Promotes Juvenile-like Plasticity in Adult Visual Cortex.

By virtue of their extensive axonal arborization and perisomatic synaptic targeting, cortical inhibitory parvalbumin (PV) cells strongly regulate principal cell output and plasticity and modulate experience-dependent refinement of cortical circuits during development. An interesting aspect of PV cell connectivity is its prolonged maturation time course, which is completed only by end of adolescence. The p75 neurotrophin receptor (p75NTR) regulates numerous cellular functions; however, its role on cortical circuit development and plasticity remains elusive, mainly because localizing p75NTR expression with cellular and temporal resolution has been challenging. By using RNAscope and a modified version of the proximity ligation assay, we found that p75NTR expression in PV cells decreases between the second and fourth postnatal week, at a time when PV cell synapse numbers increase dramatically. Conditional knockout of p75NTR in single PV neurons in vitro and in PV cell networks in vivo causes precocious formation of PV cell perisomatic innervation and perineural nets around PV cell somata, therefore suggesting that p75NTR expression modulates the timing of maturation of PV cell connectivity in the adolescent cortex. Remarkably, we found that PV cells still express p75NTR in adult mouse cortex of both sexes and that its activation is sufficient to destabilize PV cell connectivity and to restore cortical plasticity following monocular deprivation in vivo Together, our results show that p75NTR activation dynamically regulates PV cell connectivity, and represent a novel tool to foster brain plasticity in adults.SIGNIFICANCE STATEMENT In the cortex, inhibitory, GABA-releasing neurons control the output and plasticity of excitatory neurons. Within this diverse group, parvalbumin-expressing (PV) cells form the larger inhibitory system. PV cell connectivity develops slowly, reaching maturity only at the end of adolescence; however, the mechanisms controlling the timing of its maturation are not well understood. We discovered that the expression of the neurotrophin receptor p75NTR in PV cells inhibits the maturation of their connectivity in a cell-autonomous fashion, both in vitro and in vivo, and that p75NTR activation in adult PV cells promotes their remodeling and restores cortical plasticity. These results reveal a new p75NTR function in the regulation of the time course of PV cell maturation and in limiting cortical plasticity.