Acupuncture at Lianquan (CV23) acupoint has been shown to improve swallowing function in poststroke dysphagia (PSD). This improvement is supposed to be associated with the regulation of neuronal activity in the contralateral primary motor cortex (M1), while the underlying mechanism still needs to be elucidated. Perineuronal nets (PNNs) are well-known to be involved in the regulation of neuronal activity. Thus, we here aimed to detect the role of PNNs in the contralateral M1 hemisphere in the electroacupuncture (EA)-mediated effect in male mice. The results were obtained from a combination of methods, including in vitro slice electrophysiological recording, in vivo electrophysiological recording, and immunofluorescent staining in male mice. These results showed a decrease of the excitatory postsynaptic currents (sEPSCs) and no alteration of the inhibitory postsynaptic currents (sIPSCs) in the GABAergic neurons and the tonic inhibition in the excitatory neurons in the contralateral M1 after stroke induction, and EA recovered the impaired sEPSCs in the GABAergic neurons. We further found that the effect of EA-induced increase of c-Fos expression, enhancement of spike firing, potentiation of sEPSCs in the excitatory neurons, and improvement of swallowing function were all blocked by the removal of PNNs in the contralateral M1. In conclusion, the PNNs in the contralateral M1 was suggested to be participated in stroke pathogenesis and might be associated with the EA-mediated swallowing function rehabilitation of PSD in male mice. Our study provides insight into how PNNs might be involved in the mechanism of EA treatment for stroke rehabilitation.

Acupuncture can alleviate depression-like behaviors. However, the neural mechanisms behind the anti-depressive effect remain unknown. Perineuronal net (PNN) abnormalities have been reported in multiple psychiatric disorders. This study investigated the modulation and neural mechanism of PNNs in the anti-depressant process of electroacupuncture (EA) at Baihui (GV20) and Yintang (GV29) points. A rat depression model was induced by chronic unpredicted mild stress (CUMS). The results revealed that CUMS, applied for four weeks, specifically reduces PNNs around parvalbumin (PV). In addition, EA and fluoxetine treatments reverse the decrease in PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons in the medial prefrontal cortex (mPFC) after CUMS. Furthermore, EA treatment can reverse the decrease in the protein expression of PNN components (aggrecan and brevican) in the mPFC caused by stress. After EA treatment, the decreased expression of GAD67, GLuA1, and PSD95 in the mPFC induced by CUMS for four weeks was also reversed. PNN degradation in mPFC brain areas potentially interferes with the anti-depressant benefits of EA in rats with depression induced by CUMS. EA treatment did not increase PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons after PNNs degradation in the mPFC brain region of rats. This finding indicated that the mechanism of acupuncture\'s anti-depressant effect may be based on reversing the CUMS-induced decline in PNN expression, the functional impairment of γ-aminobutyric acid (GABA) neurons, and the regulation of excitatory synaptic proteins expression.

The striatal region Area X plays an important role during song learning, sequencing, and variability in songbirds. A previous study revealed that neurotoxic damage within Area X results in micro and macrostructural changes across the entire brain, including the downstream dorsal thalamus and both the upstream pallial nucleus HVC (proper name) and the deep cerebellar nuclei (DCN). Here, we specify these changes on cellular and gene expression levels. We found decreased cell density in the thalamic and cerebellar areas and HVC, but it was not related to neuronal loss. On the contrary, perineuronal nets (PNNs) in HVC increased for up to 2 months post-lesion, suggesting their protecting role. The synaptic plasticity marker Forkhead box protein P2 (FoxP2) showed a bi-phasic increase at 8 days and 3 months post-lesion, indicating a massive synaptic rebuilding. The later increase in HVC was associated with the increased number of new neurons. These data suggest that the damage in the striatal vocal nucleus induces cellular and gene expression alterations in both the efferent and afferent destinations. These changes may be long-lasting and involve plasticity and neural protection mechanisms in the areas directly connected to the injury site and also to distant areas, such as the cerebellum.

Perineuronal nets (PNNs) have an important physiological role in the retention of learning by restricting cognitive flexibility. Their deposition peaks after developmental periods of intensive learning, usually in late childhood, and they help in long-term preservation of newly acquired skills and information. Modulation of PNN function by various techniques enhances plasticity and regulates the retention of memories, which may be beneficial when memory persistence entails negative symptoms such as post-traumatic stress disorder (PTSD). In this study, we investigated the role of PTPσ [receptor-type tyrosine-protein phosphatase S, a phosphatase that is activated by binding of chondroitin sulfate proteoglycans (CSPGs) from PNNs] in retention of memories using Novel Object Recognition and Fear Conditioning models. We observed that mice haploinsufficient for PTPRS gene (PTPσ+/-), although having improved short-term object recognition memory, display impaired long-term memory in both Novel Object Recognition and Fear Conditioning paradigm, as compared to WT littermates. However, PTPσ+/- mice did not show any differences in behavioral tests that do not heavily rely on cognitive flexibility, such as Elevated Plus Maze, Open Field, Marble Burying, and Forced Swimming Test. Since PTPσ has been shown to interact with and dephosphorylate TRKB, we investigated activation of this receptor and its downstream pathways in limbic areas known to be associated with memory. We found that phosphorylation of TRKB and PLCγ are increased in the hippocampus, prefrontal cortex, and amygdaloid complex of PTPσ+/- mice, but other TRKB-mediated signaling pathways are not affected. Our data suggest that PTPσ downregulation promotes TRKB phosphorylation in different brain areas, improves short-term memory performance but disrupts long-term memory retention in the tested animal models. Inhibition of PTPσ or disruption of PNN-PTPσ-TRKB complex might be a potential target for disorders where negative modulation of the acquired memories can be beneficial.

Current methods of experimentally degrading the specialized extracellular matrix (ECM), perineuronal nets (PNNs) have several limitations. Genetic knockout of ECM components typically has only partial effects on PNNs, and knockout of the major ECM component aggrecan is lethal in mice. Direct injection of the chondroitinase ABC (ChABC) enzyme into the mammalian brain is effective at degrading PNNs in vivo but this method typically lacks consistent, localized spatial targeting of PNN degradation. PNNs also regenerate within weeks after a ChABC injection, thus limiting the ability to perform long-term studies. Previous work has demonstrated that viral delivery of ChABC in mammalian neurons can successfully degrade PNNs for much longer periods, but the effects are similarly diffuse beyond the injection site. In an effort to gain cell-specific targeting of ChABC, we designed an adeno-associated virus encoding ChABC under the control of the Cre-LoxP system. We show that this virus is effective at targeting the synthesis of ChABC to Cre-expressing mouse neurons in vivo. Although ChABC expression is localized to the Cre-expressing neurons, we also note that ChABC is apparently trafficked and secreted at projection sites, as was previously reported for the non-Cre dependent construct. Overall, this method allows for cell-specific targeting of ChABC and long-term degradation of PNNs, which will ultimately serve as an effective tool to study the function of cell-autonomous regulation of PNNs in vivo. This novel approach may also aid in determining whether specific, long-term PNN loss is an appropriate strategy for treatment of neurodevelopmental disorders associated with PNN pathology.

It is now increasingly clear that the cerebellum may modulate brain functions altered in drug addiction. We previously demonstrated that cocaine-induced conditioned preference increased activity at the dorsal posterior cerebellar vermis. Unexpectedly, a neurotoxic lesion at this region increased the probability of cocaine-induced conditioned preference acquisition. The present research aimed at providing an explanatory model for such as facilitative effect of the cerebellar lesion. First, we addressed a tracing study in which we found a direct projection from the lateral (dentate) nucleus to the ventral tegmental area (VTA) that also receives Purkinje axons from lobule VIII in the vermis. This pathway might control the activity and plasticity of the cortico-striatal circuitry. Then we evaluated cFos expression in different regions of the medial prefrontal cortex and striatum after a lesion in lobule VIII before conditioning. Additionally, perineuronal net (PNN) expression was assessed to explore whether the cerebellar lesion might affect synaptic stabilization mechanisms in the medial prefrontal cortex (mPFC). Damage in this region of the vermis induced general disinhibition of the mPFC and striatal subdivisions that receive dopaminergic projections, mainly from the VTA. Moreover, cerebellar impairment induced an upregulation of PNN expression in the mPFC. The major finding of this research was to provide an explanatory model for the function of the posterior cerebellar vermis on drug-related memory. In this model, damage of the posterior vermis would release striatum-cortical networks from the inhibitory tonic control exerted by the cerebellar cortex over VTA, thereby promoting drug effects.

BACKGROUND: To investigate whether chronic adherence to the French Nutrition and Health Program (PNNS) guidelines was associated with better cardiovascular health.
METHODS: A study nested within the SU.VI.MAX2 cohort was conducted on participants without cardiovascular risk factors. Long-term adherence to the PNNS guidelines was estimated using validated dietary scores from 2007 and 2012. Individuals who did (PNNS+) and did not (PNNS-) continuously adhere to the PNNS guidelines were included. Applanation tonometry, impedance cardiography, laser doppler flowmetry, heart rate, heart rate variability, endothelial function was used for the assessment of cardiovascular health.
RESULTS: A total of 49 subjects (mean age 65.4 ± 5.6 years, 75.5% women) had been included. Those in the PNNS+ group (n=26) were older, had a higher BMI and fat mass than those in the PNNS- group, both groups had similar metabolic parameters. After adjusting for sex, age, and BMI, PNNS+ subjects were found to have a lower heart rate (60.2 ± 8.0 vs 64.3 ± 8.4 beats/min, p=0.042), a lower heart rate × systolic blood pressure product (7166 ± 1323 vs 7788 ± 1680 beats× mmHg/min, p = 0.009), a longer diastole duration (66.7 ± 3.1% vs 64.6 ± 4.1% of the cardiac cycle duration, p=0.049), and a shorter tension-time index (2145 ± 489 vs 2307 ± 428 ms * mmHg, p=0.018) compared to the PNNS- group.
CONCLUSIONS: Long-term adherence to the PNNS guidelines had a favorable impact on heart rate, diastole duration, and myocardial oxygen consumption.
BACKGROUND: NCT01579409.

A Probabilistic Neural Network (PNN) is a statistical algorithm and consists of a grouping of multi-class data. The conventional method of detection of DNA mutations by the human eye may not detect the minute variations in PCR-SSCP bands, which may lead to false positive or false negative results. The detection by photographic images may contain a blare (noise) caused during the time of photography; therefore, image processing techniques were used to reduce image noise. PCR-SSCP gels of T2DM patients (n = 100) and controls (n = 100) were initially photographed with equal ratio of pixels and later subjected to a two-stage analysis: feature extraction and PNN. The evaluation of the results was done by quality training and the accuracy was up to 95%, and the human eye analysis showed 80% mutation detection rate. This study proves to be very reliable and gives accurate and fast detection for mutation analysis in diabetes. This method could be extended for analysis in other human diseases.

The extracellular matrix (ECM) is known to regulate important processes in neuronal cell development, activity and growth. It is associated with the structural stabilization of neuronal processes and synaptic contacts during the maturation of the central nervous system. The remodeling of the ECM during both development and after central nervous system injury has been shown to affect neuronal guidance, synaptic plasticity and their regenerative responses. Particular interest has focused on the inhibitory role of chondroitin sulfate proteoglycans (CSPGs) and their formation into dense lattice-like structures, termed perineuronal nets (PNNs), which enwrap sub-populations of neurons and restrict plasticity. Recent studies in mammalian systems have implicated CSPGs and PNNs in regulating and restricting structural plasticity. The enzymatic degradation of CSPGs or destabilization of PNNs has been shown to enhance neuronal activity and plasticity after central nervous system injury. This review focuses on the role of the ECM, CSPGs and PNNs; and how developmental and pharmacological manipulation of these structures have enhanced neuronal plasticity and aided functional recovery in regeneration, stroke, and amblyopia. In addition to CSPGs, this review also points to the functions and potential therapeutic value of these and several other key ECM molecules in epileptogenesis and dementia.